
[Federal Register Volume 81, Number 169 (Wednesday, August 31, 2016)]
[Rules and Regulations]
[Pages 60169-60224]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-20471]



[[Page 60169]]

Vol. 81

Wednesday,

No. 169

August 31, 2016

Part III





Department of Health and Human Services





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Food and Drug Administration





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21 CFR Parts 20, 201, 207, et al.





Requirements for Foreign and Domestic Establishment Registration and 
Listing for Human Drugs, Including Drugs That Are Regulated Under a 
Biologics License Application, and Animal Drugs; Final Rule

  Federal Register / Vol. 81 , No. 169 / Wednesday, August 31, 2016 / 
Rules and Regulations  

[[Page 60170]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 20, 201, 207, 314, 514, 515, 601, 607, and 1271

[Docket No. FDA-2005-N-0464 (formerly Docket No. 2005N-0403)]
RIN 0910-AA49


Requirements for Foreign and Domestic Establishment Registration 
and Listing for Human Drugs, Including Drugs That Are Regulated Under a 
Biologics License Application, and Animal Drugs

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending its 
regulations governing drug establishment registration and drug listing. 
These amendments reorganize, modify, and clarify current regulations 
concerning who must register establishments and list human drugs, human 
drugs that are also biological products, and animal drugs. The final 
rule requires electronic submission, unless waived in certain 
circumstances, of registration and listing information. This rulemaking 
pertains to finished drug products and to active pharmaceutical 
ingredients (APIs) alone or together with one or more other 
ingredients. The final rule describes how and when owners or operators 
of establishments at which drugs are manufactured or processed must 
register their establishments with FDA and list the drugs they 
manufacture or process. In addition, the rule makes certain changes to 
the National Drug Code (NDC) system. We are taking this action to 
improve management of drug establishment registration and drug listing 
requirements and make these processes more efficient and effective for 
industry and for us. This action also supports implementation of the 
electronic prescribing provisions of the Medicare Prescription Drug, 
Improvement, and Modernization Act of 2003 (MMA) and the availability 
of current drug labeling information through DailyMed, a computerized 
repository of drug information maintained by the National Library of 
Medicine.

DATES: This rule is effective on November 29, 2016. See section IV for 
compliance dates.

FOR FURTHER INFORMATION CONTACT:
    For information pertaining to human drug products: Paul Loebach, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, Rm. 2262, Silver Spring, MD 20993, 
301-796-2173.
    For information pertaining to human biological drug products or 
human cells, tissue, and cellular and tissue-based products (HCT/Ps) 
regulated solely under section 361 of the Public Health Service Act: 
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, 
Silver Spring, MD 20993, 240-402-7911.
    For information pertaining to animal drug products: Charise Kasser, 
Center for Veterinary Medicine (HFV-212), Food and Drug Administration, 
7519 Standish Pl., Rm. 2626, Rockville, MD 20855, 240-402-6816; or 
Isabel Pocurull, Center for Veterinary Medicine (HFV-226), Food and 
Drug Administration, 7519 Standish Pl., Rm. 2636, Rockville, MD 20855, 
240-402-5877.

SUPPLEMENTARY INFORMATION:

Table of Contents

Executive Summary
    Purpose of the Regulatory Action
    Summary of the Major Provisions of the Regulatory Action
    Benefits and Costs
I. Background
II. Overview of the Final Rule Including Changes to the Proposed 
Rule
    A. Overview
    B. Changes to the Proposed Rule
III. Comments on the Proposed Rule
    A. Labeling (Sec. Sec.  201.2 and 201.25)
    B. General Information (Part 207, Subpart A)
    C. Registration (Part 207, Subpart B)
    D. National Drug Code (Part 207, Subpart C)
    E. Listing (Part 207, Subpart D)
    F. Electronic Format for Registration and Listing (Part 207, 
Subpart E)
    G. Miscellaneous (Part 207, Subpart F)
    H. Human Cells, Tissues, and Cellular and Tissue-Based Products 
(Part 1271)
IV. Compliance Dates
V. Legal Authority
VI. Analysis of Environmental Impact
VII. Economic Analysis of Impacts
    A. Introduction
    B. Summary of Benefits and Costs
    C. Response to Comments on the Preliminary Impact Analysis of 
the Proposed Rule
VIII. Paperwork Reduction Act of 1995
    A. Registration Information Collection Under Part 207
    B. Listing Information Collection Under Part 207
    C. Registration and Listing Information Collection Under Part 
607
    D. Registration and Listing Information Collection Under Part 
1271
    E. Waiver Request Information
    F. Public Disclosure Exemption Requests
    G. Standard Operating Procedure for Electronic Submission
    H. Capital Costs
IX. Federalism
X. References

Executive Summary

Purpose of the Regulatory Action

    This final rule amends FDA's longstanding regulations governing 
drug establishment registration and drug listing. The amendments are 
aimed at modernizing these regulations and improving efficiency and 
reliability for FDA and drug manufacturers. These amendments also bring 
FDA's regulations governing drug establishment registration and listing 
into conformance with section 510 of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) (21 U.S.C. 360) as amended by the Food and 
Drug Administration Amendments Act (FDAAA) (Pub. L. 110-85) and the 
Food and Drug Administration Safety and Innovation Act (FDASIA) (Pub. 
L. 112-144).
    Since the 1962 Kefauver Harris amendments to the FD&C Act (Pub. L. 
87-781), drug manufacturers have been required to register their 
establishments with FDA annually. Among other things, drug 
establishment registration identifies establishments for inspection by 
FDA. In 1973, the FD&C Act was further amended to require each 
registered establishment to submit a list of drugs it manufactures. 
FDA's regulations implementing these requirements are found in part 207 
(21 CFR part 207) (pertaining to drugs and biological products 
generally) and part 607 (21 CFR part 607) (pertaining to blood and 
blood products). Manufacturers of HCT/Ps register and list either under 
part 207, part 807 (21 CFR 807), or under part 1271 (21 CFR part 1271), 
issued under authority of the Public Health Service Act (PHS Act), 
depending on the type of HCT/P product they manufacture.
    The amendments to parts 207 and 607 adopted by this final rule 
modernize those regulations and bring them into conformance with 
section 510 of the FD&C Act following recent amendments.

Summary of the Major Provisions of the Regulatory Action

    This final rule requires electronic submission, unless waived in 
certain circumstances, of drug establishment registration and listing 
information. The electronic submission requirement is consistent with 
FDAAA and with current practice.

[[Page 60171]]

    The rule makes clear that the establishment registration and 
listing obligation rests with persons who manufacture, repack, relabel, 
or salvage drug products. The rule does not require persons who act 
only as private label distributors of drug products to register 
establishments or list drugs, but allows them to submit drug listing 
information as agents acting on behalf of persons who manufacture, 
repack, relabel, or salvage drug products. The amendments make several 
adjustments to the timing and substance of the submission of 
information to register a drug establishment and list drugs 
manufactured, repacked, relabeled, or salvaged at the establishment. 
The amendments also update longstanding regulatory provisions governing 
FDA disclosure of drug registration and listing information, stating 
that with certain exceptions, establishment registration and drug 
listing information is generally available for public disclosure.
    This final rule does not include certain aspects of the proposed 
rule that were opposed by many who submitted comments. Features of the 
proposed rule that have not been finalized include most significantly: 
(1) A requirement that FDA, not registrants, develop national drug 
codes (NDCs) for assignment to listed drugs and (2) a requirement that 
the NDC appear in human-readable form on the label of each listed drug 
and provisions that would have defined the appropriate NDC for that 
purpose. As discussed in section III, revisions to the FD&C Act require 
human-readable NDCs on certain drug labels.

Benefits and Costs

    All incremental costs from the final rule are one-time costs, 
except for registrants' annually recurring costs of certifying no 
change to listings upon annual registration for part 207 registrants. 
We estimate one-time total costs of $59.7 million and recurring costs 
of $0.5 million. These costs represent total annualized costs of $9 
million when calculated at a 7-percent discount rate over 10 years, and 
$7.5 million when calculated using a 3-percent discount rate. The 
largest cost elements will be for registrants reading and understanding 
the final rule and making changes to their standard operating 
procedures.

                               Summary of Total Incremental Cost of the Final Rule
                                                  [$ millions]
----------------------------------------------------------------------------------------------------------------
                                                                     Recurring      Total costs     Total costs
                 Affected firms                   One-time costs       costs       annualized at   annualized at
                                                                     (annual)           7%              3%
----------------------------------------------------------------------------------------------------------------
Drugs and biological products (part 207)........           $48.9            $0.5            $7.5            $6.2
Human blood products (part 607).................             5.1             N/A             0.7             0.6
Human cell and tissue products (part 1271)......             5.7             N/A             0.8             0.7
                                                 ---------------------------------------------------------------
    Total \1\...................................            59.7             0.5             9.0             7.5
----------------------------------------------------------------------------------------------------------------
\1\ Total costs are annualized over a 10-year period. Recurring costs include only annual time costs of
  certifying that there are no changes to listings; these costs are unique to part 207. All estimates reflect
  rounded 2014 dollars.

    By codifying the statutory requirements of FDAAA and FDASIA, the 
final rule clarifies and completes the modernization of our electronic 
registration and listing systems. Thus, the final rule will improve 
management of the establishment registration and drug listing 
requirements and make these processes more efficient and effective for 
industry and for us. The final rule also supports implementation of the 
electronic prescribing provisions of the MMA and the availability of 
current drug labeling information through DailyMed, a computerized 
repository of drug information maintained by the National Library of 
Medicine.

I. Background

    In the Federal Register of August 29, 2006 (71 FR 51276), FDA 
proposed to amend its regulations governing drug establishment 
registration and drug listing in part 207 (proposed rule). The proposed 
rule included ancillary amendments to parts 20, 201, 314, 514, 515, 
601, 607, and 1271 (21 CFR parts 20, 201, 314, 514, 515, 601, 607, and 
1271). These amendments reorganize, modify, and clarify current 
regulations concerning who must register establishments and list human 
drugs, human drugs that are also biological products, and animal drugs. 
The proposed rule and the final rule both specify that drug 
establishment registration and drug listing information generally must 
be submitted to FDA electronically.
    After the proposed rule was published, FDAAA was adopted into law. 
FDAAA amended section 510(p) of the FD&C Act to require electronic 
submission of drug establishment registration and listing information, 
unless FDA waives the electronic submission requirement in individual 
cases. In June 2009, FDA announced publication of a guidance for 
industry on ``Providing Regulatory Submissions in Electronic Format--
Drug Establishment Registration and Drug Listing'' consistent with 
FDAAA (74 FR 26248, June 1, 2009, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) (the electronic registration 
and listing guidance). This guidance applied to establishment 
registration and listing required under part 207. It did not apply to 
information required solely under part 607 (blood and blood products), 
part 807 (devices), or part 1271 (human cells, tissues, and cellular 
and tissue-based products). FDA generally stopped receiving drug 
establishment registration and listing information required under part 
207 submitted on paper in June 2009, allowing paper submissions only if 
supported by a waiver from the electronic submission requirement in 
individual cases. This final rule is consistent with the electronic 
submission provisions of FDAAA.
    FDASIA made further amendments to section 510 of the FD&C Act in 
2012 to specify that:
     Annual registration of establishments takes place during 
the period beginning on October 1 and ending on December 31.
     The information registrants supply for annual registration 
includes a Unique Facility Identifier (UFI) for the establishment and 
includes a point-of-contact email address.
    This final rule includes changes to the proposed rule consistent 
with these statutory provisions. The electronic registration and 
listing guidance stated that FDA intended to use the Data Universal 
Numbering System (DUNS) number, assigned and managed by Dun

[[Page 60172]]

& Bradstreet, as a registration number. In 2014, FDA announced 
publication of a guidance for industry on ``Specifications of the 
Unique Facility Identifier (UFI) System for Drug Establishment 
Registration,'' (79 FR 65977, November 6, 2014, available on the 
Internet at http://www.fda.gov/Drugs under Guidances (Drugs)), in which 
FDA specified the DUNS number as the preferred UFI.

II. Overview of the Final Rule Including Changes to the Proposed Rule

A. Overview

    The final rule adopts significant amendments to FDA's regulations 
governing drug registration and listing. It modernizes these 
regulations to require electronic submission of drug establishment 
registration and listing information and to otherwise match current 
statutory requirements and FDA's information needs.
    The final rule:
     Makes minor technical amendments to Sec. Sec.  20.100, 
20.116, and 201.1 (updating citations to regulations in part 207).
     Removes from Sec.  201.2 a statement about the manner in 
which NDCs are displayed on drug labels.
     Amends Sec.  201.25 to allow an FDA Center Director to 
approve an additional bar code standard or format.
     Revises part 207 significantly.
     Amends Sec.  314.81(b)(3)(iv) (requiring holders of 
approved new drug applications (NDAs) to report the withdrawal of 
approved drug products from sale) to make it consistent with part 207.
     Makes a minor conforming amendment to Sec.  314.125(b)(11) 
(stating FDA may refuse to approve a new drug application if the drug 
will be manufactured in whole or in part in an establishment that is 
not registered and not exempt from registration under section 510 of 
the FD&C Act and part 207).
     Adds new Sec.  514.111(a)(12) stating FDA will refuse to 
approve a new animal drug application if the drug will be produced in 
whole or in part in an establishment that is not registered and is not 
exempt from registration under section 510 of the FD&C Act and part 
207.
     Makes a minor technical amendment to Sec.  515.10(b)(8), 
updating a reference to the regulations in part 207.
     Adds new Sec.  601.2(f) requiring holders of biologics 
license applications (BLAs) to report to FDA electronically in 
accordance with part 207 the withdrawal from sale of licensed 
biological products.
     Amends part 607 (ESTABLISHMENT REGISTRATION AND PRODUCT 
LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS) consistent 
with the amendments to part 207, to require electronic submission of 
establishment registration and listing information.
     Amends part 1271 (HUMAN CELLS, TISSUES, AND CELLULAR AND 
TISSUE-BASED PRODUCTS) to require electronic submission of 
establishment registration and listing information, to state that 
manufacturers of HCT/Ps that are regulated as drugs, devices, and/or 
biological products under section 351 of the PHS Act (42 U.S.C. 262) or 
under the FD&C Act are subject to registration and listing under part 
207 or part 807, and to make other revisions consistent with the 
amendments to part 207.

B. Changes to the Proposed Rule

    The final rule has been revised in response to comments received on 
the proposed rule. Our responses are discussed in section III. The 
final rule also includes several minor editorial revisions. The final 
rule makes the changes summarized in table 1.

  Table 1--Substantive Changes From the Proposed Rule to the Final Rule
------------------------------------------------------------------------
 21 CFR Section in final
           rule               Description of change from proposed rule
------------------------------------------------------------------------
201.2....................  Labeling.
                               Does not include proposed
                               revisions to Sec.   201.2 requiring human-
                               readable NDCs on labels.
201.25...................  Bar code label requirements.
                               Revises Sec.   201.25(c)(1) to
                               accommodate alternatively formatted NDCs
                               in bar codes.
                               Does not include other proposed
                               amendments to Sec.   201.25.
207.1....................  Definitions.
                               Includes definitions for the
                               terms ``finished drug product,''
                               ``unfinished drug product,'' ``bulk drug
                               substance,'' ``private label
                               distribution,'' ``registrant,'' and
                               ``outsourcing facility'' not included in
                               the proposed rule.
                               States that the definitions and
                               interpretations of terms in sections 201
                               (21 U.S.C. 321) and 510 of the FD&C Act
                               apply to the terms used in part 207, if
                               not otherwise defined in Sec.   207.1.
                               Includes revised definitions of
                               the terms ``active pharmaceutical
                               ingredient,'' ``commercial
                               distribution,'' ``content of labeling,''
                               ``importer,'' ``manufacture,'' ``private
                               label distributor,'' ``relabel,''
                               ``repack,'' and ``representative sampling
                               of any other labeling''.
207.9....................  Who does this part cover?
                            Clarifies that private label
                            distributors are subject to part 207
                            (because they must have labeler codes).
                               States that all drugs regulated
                               under a BLA, except human blood or blood
                               products regulated under part 607, are
                               subject to part 207 and clarifies that
                               for this purpose certain products are not
                               included in the phrase ``human whole
                               blood and blood products''.
                               States that HCT/Ps regulated as
                               drugs under section 505 of the FD&C Act
                               (21 U.S.C. 355) or section 351 of the PHS
                               Act are subject to part 207.
207.13...................  Who is exempt from the registration and
                            listing requirements?
                               Generally exempts from
                               registration and listing individuals or
                               establishments engaged solely in
                               recovering cells or tissues to become
                               components of a biological product at a
                               registered establishment.
                               Eliminates a reference to
                               salvagers of inactive ingredients because
                               salvaging, as defined, is performed only
                               on finished drug products.
                               Revises Sec.   207.13 to clarify
                               the applicability of part 207 to
                               medicated feeds.
                               Revises Sec.   207.13 to remove a
                               reference to HCT/Ps made unnecessary by
                               revisions to Sec.   207.9.
                               Adds an exemption for outsourcing
                               facilities registered under section 503B
                               of the FD&C Act (21 U.S.C. 353b) so as to
                               avoid duplicative registration for those
                               entities.
                               Retains the previous
                               establishment registration exemptions for
                               certain drugs entering foreign trade
                               zones and certain drugs imported for
                               export.
207.17...................  Who must register?

[[Page 60173]]

 
                               Revises Sec.   207.17(b) to state
                               that FDA will accept establishment
                               registration or listing information
                               submitted by a private label distributor
                               if it is acting as an authorized agent
                               for an establishment that manufactures,
                               repacks, relabels, or salvages drugs.
207.25...................  What information is required for
                            registration?
                               Revises proposed Sec.   207.25 to
                               include the UFI required as part of
                               establishment registration under FDASIA.
207.29...................  What are the requirements for reviewing and
                            updating registration information?
                               Revises Sec.   207.29 to specify
                               that registrants must review and update
                               registration information between October
                               1 and December 31 each year, consistent
                               with FDASIA.
207.33...................  What is the National Drug Code (NDC), how is
                            it assigned, and what are its requirements?
                               Allows for 10- or 11-digit NDCs,
                               consistent with a longstanding statement
                               in Sec.   207.35(b)(2)(i), as it read
                               prior to this final rule, that FDA will
                               expand the NDC labeler code from 5 to 6
                               numeric characters when the available 5-
                               character code combinations are
                               exhausted.
                               States that registrants will
                               propose NDCs for assignment by FDA.
                               Includes formatting requirements
                               for registrants to follow when
                               formulating their own proposed NDCs.
                               Allows for alternatively
                               formatted NDCs for certain HCT/Ps.
                               Explains how a labeler code can
                               be obtained.
                               Allows registrants to reserve an
                               NDC for a drug product under development.
                               Eliminates proposed Sec.
                               207.33(c). (What information must a
                               manufacturer submit before we will assign
                               an NDC number to a drug?)
                               Adds some information elements
                               described in proposed Sec.   207.33(c) to
                               the drug listing information now
                               described in Sec.   207.49 (Added to the
                               listing information required under Sec.
                               207.49 are the names of inactive
                               ingredients in the listed drug and in the
                               case of an unfinished drug, the number
                               assigned to the Drug Master File or
                               Veterinary Master File, if any, that
                               describes the manufacture of the drug).
                               The option to submit an approved
                               U.S. application number instead of a list
                               of inactive ingredients for a finished
                               drug product (as proposed in Sec.
                               207.33(c)) is not retained in Sec.
                               207.49 of this final rule.
207.35...................  What changes require a new NDC?
                               Introduces new Sec.   207.35 to
                               more clearly explain what changes to
                               drugs require a new NDC and does not
                               include inactive ingredient changes in
                               this section.
207.37...................  What restrictions pertain to the use of the
                            NDC?
                               Revises Sec.   207.37 to state
                               that a product may be deemed to be
                               misbranded if an NDC is used improperly.
207.41...................  Who must list drugs and what drugs must they
                            list?
                               Revises Sec.   207.41 to clarify
                               the manner in which human drugs that are
                               manufactured, repacked, or relabeled for
                               private label distribution are listed.
207.45...................  When, after initial registration of an
                            establishment, must drug listing information
                            be submitted?
                               Revises Sec.   207.45 to state
                               that drug listing must take place no
                               later than 3 calendar days after initial
                               registration of an establishment, rather
                               than ``at the time of'' initial
                               registration.
207.49...................  What listing information must a registrant
                            submit for a drug it manufactures?
                               Revises Sec.   207.49 to reflect
                               that registrants will propose their own
                               NDCs under the final rule.
                               Eliminates the requirement of
                               proposed Sec.  Sec.   207.49(f),
                               207.53(c), and 207.54(b)(4) (which would
                               have required foreign establishments to
                               identify importers when listing drugs
                               they manufacture, repack, relabel, or
                               salvage). (This is now reported only as
                               establishment registration information
                               for foreign establishments.).
                               Expands the language of proposed
                               Sec.   207.49(d) (now Sec.
                               207.49(a)(11)) to make clear that a
                               registrant's own establishment(s) must be
                               identified in drug listing information as
                               well as other establishments involved in
                               the production of unfinished drugs
                               received by the registrant and to require
                               identification of all such establishments
                               using their UFIs.
                               Removes from proposed Sec.
                               207.49 the option to provide an approved
                               U.S. application number instead of
                               labeling.
                               Revises Sec.   207.49 (also Sec.
                               Sec.   207.1 and 207.53) to categorize
                               certain drug products according to
                               whether they are subject to sections 505
                               or 512 of the FD&C Act (21 U.S.C. 355 or
                               360b) or section 351 of the PHS Act,
                               rather than whether registrants regard
                               them as subject to those provisions.
                               Adds Sec.  Sec.
                               207.49(a)(15)(iv) and 207.53(d)(4) to
                               require the submission of labels for
                               listed drugs not elsewhere described in
                               Sec.  Sec.   207.49(a)(14) and 207.53(d).
                               Clarifies in new Sec.  Sec.
                               207.49(a)(15) and 207.53(f) the
                               information a registrant must submit when
                               listing a human drug manufactured for
                               private label distribution.
                               Adds Sec.   207.49(b) to describe
                               drug listing information that is
                               requested of registrants but not
                               required.
                               Adds Sec.   207.49(a)(2) so that
                               drug listing information includes package
                               size and type.
207.53...................  What listing information must a registrant
                            submit for a drug that it repacks or
                            relabels?
                               Shifts from proposed Sec.
                               207.33(d)(1)(iii) to new Sec.   207.53(b)
                               the requirement that for a repacked or
                               relabeled drug, registrants identify the
                               NDC assigned to the finished drug
                               received by the registrant for repacking
                               or relabeling and exempts repackaged
                               medical gases from this requirement.
                               Requires identification of
                               establishments where repacking, or
                               relabeling is performed based on their
                               UFIs rather than by their registration
                               numbers.
                               Clarifies that all current
                               labeling (new labeling) for a repacked or
                               relabeled drug must be submitted, not
                               only the changed labeling.
                               Specifies that for animal drugs
                               subject to section 512 of the FD&C Act,
                               all current labeling is submitted,
                               whereas a copy of the current label, and
                               other information, is submitted for other
                               animal drugs.
207.54...................  What listing information must a registrant
                            submit for a drug that it salvages?
                               Requires identification of
                               establishments where salvaging is
                               performed by their UFIs rather than by
                               their registration numbers.
                               Deletes references to salvaged
                               drugs distributed by private label
                               distributors.
207.57...................  What information must registrants submit when
                            updating listing information and when?
                               Revises proposed Sec.   207.57 to
                               improve clarity and to delete the
                               proposed requirement that registrants
                               routinely update information provided
                               under Sec.   207.55.

[[Page 60174]]

 
                               Allows registrants to submit a
                               blanket ``no changes'' certification
                               applicable to listing information they
                               have previously submitted electronically,
                               rather than making product-by-product
                               ``no changes'' certifications for
                               individual listed drugs.
207.61...................  How is registration and listing information
                            provided to FDA?
                               Revises Sec.   207.61 to improve
                               clarity, to state that we may
                               periodically issue guidance on electronic
                               registration and listing, and to clarify
                               that when foreign language labeling is
                               used under Sec.   201.15(c), the content
                               of labeling must be submitted in that
                               foreign language along with an accurate
                               English translation.
                               Removes the option to submit
                               advertisements and certain labeling in
                               paper format, consistent with the
                               electronic submission requirement of
                               section 510(p) of the FD&C Act, as
                               amended by FDAAA.
207.65...................  How can a waiver of the electronic submission
                            requirement be obtained?
                               Clarifies that requests for
                               waivers of the electronic submission
                               requirement cannot be relied upon until
                               FDA grants them.
                               States more broadly the
                               conditions under which FDA will grant
                               waiver requests.
                               Specifies that waiver requests
                               must be submitted in writing and must
                               state reasons why electronic submission
                               is not reasonable for the registrant.
                               States that FDA will specify
                               terms of waivers and may limit their
                               duration.
207.69...................  What are the requirements for an official
                            contact and a United States agent?
                               Revises proposed Sec.   207.69 to
                               state that designated official contacts
                               and United States agents are both
                               responsible for reviewing, disseminating,
                               routing, and responding to all
                               communications from FDA, including
                               emergency communications.
207.77...................  What legal status is conferred by
                            registration and listing?
                               Includes minor revisions to
                               improve clarity and mentions the UFI that
                               will be used to identify establishments.
207.81...................  What registration and listing information
                            will FDA make available for public
                            disclosure?
                               Reorganizes Sec.   207.81 so that
                               registration and listing information that
                               will be disclosed is described in
                               paragraph (a), and exceptions are
                               described in paragraphs (b) and (c).
                               Categorizes updated drug listing
                               information submitted under Sec.   207.57
                               as generally disclosable.
                               Adds Sec.   207.81(b)(2) to make
                               explicit that FDA will generally not
                               disclose the names of inactive
                               ingredients in listed drug products if
                               the registrant makes a valid assertion of
                               confidentiality.
                               Categorizes the information
                               submitted to reserve an NDC under new
                               Sec.   207.33(d)(3) as generally not
                               disclosable.
                               Categorizes the identities of the
                               establishments involved in manufacturing,
                               repacking, relabeling, or salvaging
                               listed drugs as generally not
                               disclosable.
                               Categorizes as generally not
                               disclosable the NDC assigned to an
                               unfinished drug received by a registrant
                               for use in the manufacture of a listed
                               drug reported under Sec.   207.49(a)(12)
                               (i.e., the association between the
                               unfinished drug and the listed drug is
                               generally not disclosable).
                               No longer categorizes the NDC
                               assigned to a drug immediately before it
                               is received by a registrant for salvaging
                               as generally not disclosable (because the
                               NDC assigned to a drug does not change
                               when a drug is merely salvaged and not
                               also repackaged or relabeled).
314.81...................  Other postmarketing reports (reporting the
                            discontinuation of a drug that is the
                            subject of an approved NDA).
 .                             Renumbers proposed Sec.
                               314.81(b)(3)(iii) as Sec.
                               314.81(b)(3)(iv) and revises this section
                               to provide for electronic or written
                               submissions in certain circumstances,
                               under both paragraphs (a) and (b).
601.2(f).................  Applications for biologics licenses
                            (reporting the discontinuation of a drug
                            that is licensed under a BLA).
                               Revises proposed Sec.   601.2(f)
                               to reference the electronic submission
                               requirement of Sec.   207.61 and the
                               waiver provision of Sec.   207.65 and to
                               clarify that the date on which the
                               product is expected to be no longer in
                               commercial distribution must be reported
                               rather than the ``date of withdrawal from
                               sale''.
607.1....................  Scope (Establishment registration and product
                            listing for manufacturers of human blood and
                            blood products.)
                               Adds a new scope provision (Sec.
                                607.1) to part 607 for clarity.
607.3....................  Definitions (Establishment registration and
                            listing for blood and blood products).
                               Adds a definition of ``foreign''.
                               Revises the proposed definition
                               of ``importer''.
607.22...................  How to register blood product establishments
                            and list blood products.
                               Revises proposed Sec.   607.22 to
                               remove references to Form FDA 2830 and to
                               state that blood product establishment
                               registration and blood product listing
                               must be transmitted to FDA electronically
                               through the Blood Establishment
                               Registration and Product Listing system,
                               unless FDA waives the electronic
                               submission requirement in individual
                               cases.
607.25...................  Information required for establishment
                            registration and blood product listing.
                               Removes references to Form FDA
                               2830.
                               Requires submission of a UFI when
                               registering blood and blood product
                               establishments along with a registration
                               number if previously assigned by FDA.
                               Adds the UFI of the parent
                               establishment to blood product listing
                               information required under Sec.
                               607.25(b)(3).
607.26...................  Amendments to establishment registration.
                               Revises Sec.   607.26 regarding
                               amendments to establishment registration
                               to reference the Blood Establishment
                               Registration and Listing System in place
                               of Form FDA 2830.
                               Clarifies that 5 days refers to 5
                               calendar days in this section.
 
607.30...................  Updating blood product listing information.
                               Revises Sec.   607.30 regarding
                               updates to blood product listing
                               information to reference the Blood
                               Establishment Registration and Listing
                               System in place of Form FDA 2830.
607.37...................  Public disclosure of establishment
                            registration and blood product listing
                            information.
                               Revises Sec.   607.37 to remove
                               references to Form FDA 2830.
                               Structures Sec.   607.37 in a way
                               that matches Sec.   207.81 (public
                               disclosure of drug registration and
                               listing information).
607.40...................  Establishment registration and blood product
                            listing requirements for foreign blood
                            product establishments.
                               Retains the exemptions applicable
                               to foreign trade zones and products
                               imported under section 801(d)(4) of the
                               FD&C Act (21 U.S.C. 381(d)(4)).

[[Page 60175]]

 
                               Revises proposed Sec.   607.40 to
                               state more broadly the circumstances
                               under which FDA will waive the electronic
                               submission requirement for foreign blood
                               product establishments.
607.80...................  Applicability of part 607 to licensed
                            devices.
                               Adds a new Sec.   607.80
                               clarifying the applicability of part 607
                               to certain licensed devices.
1271.1...................  What are the purpose and scope of this part?
                            (HCT/Ps)
                               Adds the word ``electronic'' in
                               place of ``unified'' in Sec.   1271.1.
1271.3...................  How does FDA define important terms in this
                            part?
                               Revises the definition of
                               ``importer'' in proposed Sec.
                               1271.3(mm) to include ``at the time of
                               entry''.
1271.20..................  If my HCT/Ps do not meet the criteria in Sec.
                              1271.10, and I do not qualify for any of
                            the exceptions, what regulations apply?
                               Adds a further amendment to Sec.
                                1271.20 to indicate that subpart B of
                               part 1271 (procedures for registration
                               and listing) does not apply to HCT/Ps
                               that do not meet the criteria set out in
                               Sec.   1271.10(a). (In other words, HCT/
                               Ps not regulated solely under section 361
                               of the PHS Act are subject to
                               registration and listing under part 207
                               or part 807 rather than part 1271.)
1271.25..................  What information is required for
                            establishment registration and HCT/P
                            listing?
                               Removes from proposed Sec.
                               1271.25(a)(6) the requirement that each
                               foreign HCT/P establishment designate
                               only one United States agent.
                               Removes a reference to Form FDA
                               3356 in proposed Sec.   1271.25(c)(4).
                               Revises proposed Sec.
                               1271.25(d) to clarify that it pertains to
                               HCT/Ps regulated under BLAs and to state
                               that establishment registration and
                               listing information for such products
                               must be submitted in accordance with the
                               electronic submission requirements of
                               part 207, subpart E.
------------------------------------------------------------------------

    This final rule does not include the proposed amendments to 
Sec. Sec.  330.1, 610.60, and 610.61, all of which dealt with NDCs on 
labels. This final rule also does not include the proposed minor 
amendment to Sec.  1271.37 (regarding public disclosure of HCT/P 
establishment registration and listing information) in light of the 
technical amendments adopted on April 3, 2015 (80 FR 18087).
    Some changes from the proposed rule not addressed in section III 
(Comments on the Proposed Rule) are addressed in the following 
paragraphs.
    Active pharmaceutical ingredient: To prevent confusion, we proposed 
to replace the term ``bulk drug substance'' with the more descriptive 
term ``active pharmaceutical ingredient.'' This change is retained in 
the final rule. Sections 503A(b)(1)(A) and 503B(a)(2) of the FD&C Act 
(21 U.S.C. 353a(b)(1)(A) and 353b(a)(2)), however, refer specifically 
to the definition of ``bulk drug substance'' within part 207. To ensure 
conformity with the FD&C Act, both ``bulk drug substance'' and ``active 
pharmaceutical ingredient'' are defined in Sec.  207.1 of the final 
rule. As intended by the proposed rule, ``active pharmaceutical 
ingredient'' will have the same meaning as ``bulk drug substance.''
    Salvage: In this final rule, the term ``salvage'' is defined to 
mean the act of segregating out those finished drug products that may 
have been subjected to improper storage conditions (such as extremes in 
temperature, humidity, smoke, fumes, pressure, age, or radiation) for 
the purpose of returning the products to the marketplace and includes 
applying manufacturing controls such as those required by current good 
manufacturing practice in parts 210 and 211 (21 CFR parts 210 and 211). 
Substantively, this matches the definition of ``drug product 
salvaging'' included in the proposed rule, but the words have been 
rearranged for greater clarity. This final rule also includes a 
definition for the term ``salvager.''
    Establishment registration number and Unique Facility Identifier: 
We proposed to define the term ``establishment registration number'' in 
Sec.  207.1 to mean ``the number assigned by FDA to the establishment 
during the establishment registration process required in this part.'' 
The final rule changes the definition of ``establishment registration 
number'' slightly to state that the number is assigned ``after'' the 
registration process, rather than ``during.''
    The establishment registration number identifies establishments for 
inspection by FDA. Historically, an establishment registration number 
is assigned to each establishment of each manufacturer, repacker, 
relabeler, or salvager after the initial registration, when such 
activities begin. In the preamble to the proposed rule, we explained 
that ``[c]urrently, the FDA Establishment Identifier (FEI) will be the 
number we assign as the establishment registration number. In the 
future, however, we may use a different number as the establishment 
registration number'' (71 FR 51276 at 51288).
    After the proposed rule was published, FDASIA amended section 510 
of the FD&C Act to require persons subject to the drug establishment 
registration requirement to submit a UFI. In the electronic 
registration and listing guidance, FDA stated that it intended to use 
the DUNS number, assigned and managed by Dun & Bradstreet, as a 
registration number. To implement the UFI provision of FDASIA, FDA also 
issued guidance in 2014 that specified the DUNS number as the preferred 
UFI.\1\
---------------------------------------------------------------------------

    \1\ See the guidance for industry ``Specification of the Unique 
Facility Identifier (UFI) System for Drug Establishment 
Registration,'' November 2014, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs).
---------------------------------------------------------------------------

    Under the final rule, the establishment registration number and the 
UFI are two distinct numbers. For now, FDA will continue to assign an 
FEI as the establishment registration number after an establishment is 
registered for the first time. The final rule requires registrants to 
submit the establishment registration number (currently the FEI), ``if 
previously assigned by FDA,'' under Sec.  207.25. Someone registering 
an establishment for the first time is not expected to have a 
registration number for the establishment. Such a registrant is 
required to submit its registration number at the time of the first 
annual review and update of registration information under Sec.  
207.29(b) of this final rule and is encouraged to submit the 
registration number sooner, as soon as it is received from FDA. The 
establishment registration number does not need to be submitted at the 
time of each annual registration update under Sec.  207.29 unless the 
establishment registration number has changed. Likewise, the UFI, 
currently specified as

[[Page 60176]]

the DUNS number, must be submitted when registering an establishment 
for the first time under Sec.  207.25. The UFI does not need to be 
submitted at the time of each annual registration update under Sec.  
207.29 unless the UFI has changed.
    Bar code label requirements (Sec.  201.25): As explained in section 
III, this final rule does not include two proposed amendments to Sec.  
201.25. It does, however, include a minor new amendment to Sec.  
201.25. To accommodate the possibility of alternatively formatted NDCs 
in bar codes, Sec.  201.25 is amended in this final rule to allow FDA's 
Center Directors to approve additional standards or formats for bar 
codes.
    Submission of approved U.S. application number instead of inactive 
ingredients (Sec.  207.33(c)(2)): Information registrants would have 
submitted under Sec.  207.33(c) of the proposed rule to obtain an NDC 
has been shifted to drug listing information required under Sec.  
207.49 of this final rule. Under Sec.  207.49(a)(5) of this final rule, 
a registrant must provide the name of each inactive ingredient in a 
listed drug it manufactures. The option to submit an approved 
application number instead of a list of inactive ingredients is not 
retained in the final rule because FDA is not currently able to pull 
inactive ingredient information from approved applications to our drug 
listing systems.

III. Comments on the Proposed Rule

    In the Federal Register of October 31, 2006 (71 FR 63726), FDA 
announced an extension of the comment period for this rulemaking and a 
public meeting to discuss the proposed changes to the NDC system 
presented in the proposed rule. The public meeting was held on December 
11, 2006. In the Federal Register of February 8, 2007 (72 FR 5944), FDA 
announced a reopening of the comment period because technical problems 
prevented some persons from submitting comments electronically on the 
last day of the previous comment period. The Agency received numerous 
comments, including oral presentations made at the December 2006 public 
meeting and approximately 200 written comments placed in the docket. 
Comments were received from prescription and nonprescription drug 
manufacturers and related companies, trade associations representing 
drug manufacturers and other interested parties, academic institutions, 
and professional associations.
    The docket for this rulemaking, Docket No. FDA-2005-N-0464, was 
also used to collect comments on FDA's draft guidance for industry 
entitled ``Providing Regulatory Submissions in Electronic Format--Drug 
Establishment Registration and Drug Listing'' (74 FR 26248). In this 
final rule, we are responding to comments that pertain to the 
rulemaking, i.e., comments that relate to the changes in regulations 
proposed on August 29, 2006.
    To make it easier to identify comments and our responses, the word 
``Comment,'' in parentheses, appears before the comment's description, 
and the word ``Response,'' in parentheses, appears before our response. 
We have numbered each comment to help distinguish between different 
comments. Similar comments are grouped together under the same number. 
The number assigned to each comment is purely for organizational 
purposes and does not signify the comment's value or importance or the 
order in which comments were received.

A. Labeling (Sec. Sec.  201.2 and 201.25)

    The proposed rule included amendments to Sec.  201.2 that would 
have required drugs subject to the listing requirement of part 207 to 
have labels that bear the appropriate NDC in human-readable form. As 
discussed in this document, this final rule does not include the 
proposed amendments that would have made human-readable NDCs mandatory 
on drug labels.
    Section 201.2 currently states that NDCs are ``requested but not 
required'' to appear on all drug labels. Section 201.25 currently 
requires bar codes on prescription human drug labels with certain 
exceptions and on certain nonprescription human drug labels. Section 
201.25(c) currently specifies that each bar code must contain, at a 
minimum, the appropriate NDC.
    Sections 201.2 and 201.25 currently do not specify which NDC should 
appear on labels and in bar codes apart from referring to it as ``the 
appropriate'' NDC (Sec.  201.25(c)). This implies that the NDC 
appearing on a drug's label match an NDC under which the drug is 
appropriately listed under part 207.
1. NDC Numbers (Sec.  201.2)
    Pharmacists and health care providers use NDCs currently appearing 
on drug labels in a variety of ways, including to help prevent 
medication errors and to process prescription drug reimbursement 
claims. We believe there is currently a high level of cooperation with 
FDA's request in Sec.  201.2 that NDCs appear in human-readable form on 
labels, as drug manufacturers recognize the importance of this 
information.
    In addition to making human-readable NDCs on drug labels mandatory, 
the proposed rule would have specified which NDC must appear on labels. 
Specifically, proposed Sec.  201.2(b) sought to define the appropriate 
NDC for this purpose as being that of the last manufacturer, repacker, 
relabeler, or private label distributor responsible for the drug 
immediately before it is received by the wholesaler or retailer.
    (Comment 1) Several comments recognized the importance of having 
NDCs in human-readable form on labels, but many objected to FDA's 
proposed provisions defining the appropriate NDC in proposed Sec.  
201.2(b). In particular, certain repackers objected to the proposed 
requirement that a repacker's NDC, rather than that of the original 
manufacturer, appear on the labels of repackaged drug products.
    (Response) This final rule does not include the proposed amendments 
to Sec.  201.2 that would have made human-readable NDCs mandatory on 
drug labels. It includes only a conforming amendment to that section 
(replacing the reference to Sec.  207.3(b)(3) with an updated reference 
to new Sec.  207.1).
    The Drug Quality and Security Act (DQSA) (Pub. L. 113-54) of 2013 
includes as Title II the Drug Supply Chain Security Act (DSCSA). The 
DSCSA requires drug manufacturers and repackagers (as defined in 
sections 581(10) and 581(16) of the FD&C Act, respectively) to affix or 
imprint a product identifier on packages for certain prescription drugs 
for human use. Under section 581(14) of the FD&C Act, a ``product 
identifier'' is a standardized graphic that includes, in both human-
readable form and on a machine-readable data carrier, the 
``standardized numerical identifier,'' lot number, and expiration date 
of the product. The NDC is one component of the standardized numerical 
identifier. FDA has determined that because the DSCSA requires the 
inclusion of NDCs on certain prescription drug labels (as part of a 
product identifier), it is unnecessary to include the proposed 
amendments to Sec.  201.2 in this final rule.
    Our determination that the proposed amendments to Sec.  201.2 
should not be finalized renders moot many comments concerning 
identification of the appropriate NDC for labeling purposes, along with 
placement and formatting issues. Therefore, we do not respond to those 
comments.
    The DSCSA does not require manufacturers or repackagers to affix or 
imprint product identifiers on nonprescription human drug products or 
on animal drugs. Therefore, we will maintain the status quo for those 
drug products, meaning FDA will continue to request that NDCs in human-
readable

[[Page 60177]]

form appear on all drug labels and in all drug labeling, as indicated 
in Sec.  201.2. We may revisit a regulatory requirement that human-
readable NDCs appear on the labels of nonprescription human drug 
products and animal drugs in the future.
2. Bar Code Label Requirements (Sec.  201.25)
    Section 201.25 currently requires that a human drug product's NDC 
be included in its bar code. We proposed to amend Sec.  201.25 in two 
minor ways: (1) To add a cross-reference to proposed new Sec.  
201.2(b), which would have described the ``appropriate NDC'' for 
labeling purposes and (2) to add new Sec.  201.25(e) stating that a bar 
code may be displayed on certain drug product labels voluntarily but 
only if it meets the requirements of Sec.  201.25(c). Neither proposed 
amendment to Sec.  201.25 is retained in the final rule.
    (Comment 2) The Animal Health Institute expressed concern that 
proposed Sec.  201.25(e) would unreasonably burden its members who, 
although they are not currently required by Sec.  201.25 to place bar 
codes on animal drug labels (because it applies to human drugs), may do 
so for logistical reasons. They asked that the animal health industry 
be exempt from the requirement to include an NDC in any bar codes 
appearing on animal drug labels. Similar comments were received from 
manufacturers of allergenic extracts. Allergenic extracts are currently 
exempt from the bar code requirement (see Sec.  201.25(b)(1)(i)(B)). 
Commenters explained that manufacturers of allergenic extracts may 
place bar codes on their labels for inventory, warehousing, and other 
logistical purposes. They objected to proposed Sec.  201.25(e) to the 
extent that it would require such bar codes to include NDCs.
    (Response) FDA has not retained proposed Sec.  201.25(e) in this 
final rule.
    (Comment 3) A group of comments asserted that 11-digit NDCs cannot 
be encoded into a bar code that meets European Article Number/Uniform 
Code Council or Health Industry Business Communications Council 
standards, as required by current Sec.  201.25(c). Another comment 
urged FDA to remove the NDC from bar codes.
    (Response) This final rule acknowledges that 10-digit NDCs will be 
exhausted at some point in the future as a mathematical inevitability. 
As discussed in our response to Comment 52, this final rule reduces the 
number of occasions when a change to a drug requires a new NDC under 
Sec.  207.35. This final rule also amends Sec.  201.25 to allow FDA's 
Center Directors to approve additional bar code standards and formats.
    As discussed in response to Comment 1, the DSCSA requires the 
inclusion of product identifiers on prescription human drug labels and 
defines ``product identifier'' to mean a standardized graphic that 
includes, in both human-readable form and on a machine-readable data 
carrier the standardized numerical identifier, lot number, and 
expiration date of the product. The standardized numerical identifier, 
a component of the product identifier, is comprised of the NDC and a 
serial number.
    FDA continues to recognize the importance of NDCs on drug labels in 
both machine-readable and human-readable form. We remind manufacturers 
of the current requirement in Sec.  201.25 that bar codes on human drug 
labels include the appropriate NDC, and we encourage manufacturers to 
continue to provide the NDC in human-readable form on drug labels where 
not required by the DSCSA.

B. General Information (Part 207, Subpart A)

1. What definitions and interpretations of terms apply to this part? 
(Sec.  207.1)
    The proposed rule included a set of terms and definitions in 
Sec. Sec.  207.1, 607.3, and 1271.3. These definitions are retained in 
the final rule with several modifications. Additionally, the final rule 
includes definitions for the terms ``finished drug product,'' 
``unfinished drug product,'' ``bulk drug substance,'' ``outsourcing 
facility,'' ``private label distribution,'' and ``registrant'' in Sec.  
207.1 and a definition of ``foreign'' in Sec.  607.3.
    a. Commercial distribution. In the proposed rule, the definition of 
``commercial distribution'' excluded ``the internal or interplant 
transfer of an active pharmaceutical ingredient between registered 
establishments within the same parent, subsidiary, and/or affiliate 
company.''
    In the final rule, the definition does not include the phrase ``an 
active pharmaceutical ingredient'' so that internal or interplant 
transfers between such registered establishments are not treated as 
commercial distribution under part 207, whether the transfer involves 
active pharmaceutical ingredients, other unfinished drug products, or 
finished drug products.
    (Comment 4) A comment suggested that the definition of ``commercial 
distribution'' be revised to exclude transfers between a registered 
establishment and a marketing authorization holder when the two are in 
a contractual relationship. Otherwise, this comment argued, products 
marketed by private label distributors who employ contract 
manufacturers are held to a higher burden of documentation than 
products manufactured and distributed by the same entity.
    (Response) We disagree with the suggestion that a transfer of drugs 
from a contract manufacturer to another contracting party should not 
qualify as commercial distribution. Such an exemption would interfere 
with FDA's ability to track drugs and establishments for inspection. 
However, by revising the definition of ``commercial distribution'' to 
exclude internal or interplant transfers of drugs, including active 
pharmaceutical ingredients, other unfinished drugs, and finished drug 
products, between registered establishments under common ownership and 
control, we have reduced the drug listing burden generally. This 
exclusion accommodates the common practices of specialized 
manufacturing at different registered establishments under common 
ownership and control. This practice often results in multiple internal 
and interplant transfers of these materials prior to marketing, which 
we do not consider commercial distribution for registration and listing 
purposes.
    b. Content of labeling. The proposed rule included a multipart 
definition for the term ``content of labeling'' with separate 
provisions applicable to:
     Human prescription drugs that the manufacturer regards as 
subject to section 505 of the FD&C Act or section 351 of the PHS Act, 
i.e., subject to premarket approval from FDA;
     Human prescription drugs that the manufacturer regards as 
not subject to section 505 of the FD&C Act or section 351 of the PHS 
Act;
     Human nonprescription drugs; and
     Animal drugs.
    The term ``content of labeling'' was used in the proposed rule to 
describe some, but not all, labeling that must be submitted with drug 
listing information. For example, proposed Sec.  207.49(g)(2)(i) stated 
that listing information for certain human over-the-counter (OTC) drugs 
must include ``all current labeling . . . including the content of 
labeling.'' Content of labeling is defined in a very similar way in the 
final rule with deletion of the phrase ``that the manufacturer regards 
as'' and the addition of a reference to the labeling requirements for 
veterinary drugs in 21 CFR part 201.

[[Page 60178]]

    We removed the language ``that the manufacturer regards as subject 
to section 505 [or 512] of the FD&C Act or section 351 of the PHS Act'' 
and added in its place language that refers to drugs as being either 
subject or not subject to those provisions. We made this change after 
determining that the manner in which content of labeling is defined 
should not depend on a manufacturer's subjective understanding or 
intent with respect to sections 505 or 512 of the FD&C Act or section 
351 of the PHS Act.
    The revised definition includes, among others, the category ``human 
prescription drugs that are not subject to section 505 of the FD&C Act 
or section 351 of the PHS Act.'' We have retained this construction 
even though FDA considers it unlikely that any currently marketed human 
prescription drug product is grandfathered or is otherwise not a new 
drug subject to those provisions. However, the Agency recognizes that 
the existence of such drugs is at least theoretically possible. No part 
of this final rule is a finding as to the legal status of any 
particular drug product.
    Regarding animal drugs, in part four of the definition of ``content 
of labeling'' and in other places throughout this final rule, the 
phrase ``subject to section 512'' means, for purposes of this final 
rule, drugs meeting the definition of ``new animal drug'' as that term 
is defined in section 201(v) of the FD&C Act, and which therefore are 
subject to some or all of the provisions relating to new animal drugs 
found in section 512 of the FD&C Act. This term includes not only new 
animal drugs that are approved under section 512 but also new animal 
drugs that are conditionally approved under section 571 of the FD&C Act 
(21 U.S.C. 360ccc) or indexed under section 572 of the FD&C Act (21 
U.S.C. 360ccc-1). The phrase ``all other animal drugs'' as used in 
provisions of this final rule at Sec. Sec.  207.49(a)(15)(iii) and 
207.53(d)(3) describing the labeling registrants must provide as part 
of the listing for an animal drug, refers to animal drugs that do not 
meet the definition of new animal drug found in section 201(v) of the 
FD&C Act (e.g., grandfathered animal drugs). Although the Agency 
recognizes that the existence of such animal drugs is theoretically 
possible, we believe it is unlikely that any currently marketed animal 
drug product is grandfathered or otherwise not a ``new animal drug'' 
subject to section 512 of the FD&C Act.
    (Comment 5) Commenters asked FDA to clarify how content of labeling 
differs from package inserts and final printed labeling.
    (Response) A prescription human drug product's FDA-approved 
labeling is sometimes referred to as a ``package insert'' or as 
``professional labeling.'' In defining the term ``content of 
labeling,'' for human drugs, we use the phrase ``prescription drug 
labeling'' (instead of ``package insert'' or ``professional labeling'') 
to mean FDA-approved labeling for prescription drug products described 
in Sec. Sec.  201.56, 201.57, and 201.80. For human prescription drugs 
that are subject to section 505 of the FD&C Act or section 351 of the 
PHS Act, content of labeling is defined as the content of the 
prescription drug labeling. For human OTC drugs, content of labeling is 
not defined in these terms; it includes ``all text, tables, and figures 
including the drug facts labeling required by Sec.  201.66.'' For 
animal drugs, ``content of labeling'' is defined to mean labeling that 
accompanies the drug that is necessary to enable safe and proper 
administration of the drug. This would generally include package 
inserts and final printed labeling. Sections 207.49 and 207.53 require 
submission of labeling with drug listing information. In most cases, 
all current labeling must be submitted, including the content of 
labeling.
    (Comment 6) A comment stated that FDA should more clearly delineate 
between the terms ``label'' and ``labeling'' throughout the rulemaking, 
rather than using the term ``labeling'' to refer to both. This comment 
pointed out that the proposed rule's definition of content of labeling 
for human OTC drugs referred to ``labeling required by Sec.  201.66,'' 
but Sec.  201.66 pertains to information appearing on the ``outside 
container or wrapper of the retail package, or the immediate container 
label if there is no outside container or wrapper'' (Sec.  201.66(c)).
    (Response) We have clarified in Sec.  207.1(a) of the final rule 
that the definitions and interpretations of terms in sections 201 and 
510 of the FD&C Act apply to the terms used in part 207 unless 
otherwise defined. Accordingly, the term ``label'' means a display of 
written, printed, or graphic matter upon the immediate container of any 
article consistent with section 201(k) of the FD&C Act. The term 
``labeling'' more broadly includes both immediate container labels and 
other written, printed, or graphic matter accompanying such article 
consistent with section 201(m) of the FD&C Act. When we intend to refer 
only to immediate container or package labels, we use the term 
``label.'' More often, we use the broader term ``labeling'' in this 
final rule to encompass both immediate container labels and/or other 
written, printed, or graphic matter accompanying the drug, as the 
labeling definition in section 201(m) of the FD&C Act has been 
interpreted. The term ``content of labeling'' is defined slightly 
differently for human prescription drugs, human OTC drugs, and animal 
drugs, and the term is intended to encompass both labels and labeling.
    The proposed rule (proposed Sec.  207.1) referred only to 
definitions in section 510 of the FD&C Act, and the preamble to the 
proposed rule suggested that reference to the definitions in section 
201 of the FD&C Act was intentionally omitted (71 FR 51276 at 51285). 
Consistent with 21 CFR 1.1(b), this final rule clarifies that the 
definitions in section 201 of the FD&C Act apply to the terms used in 
part 207.
    c. Establishment. We proposed to define ``establishment'' in Sec.  
207.1 as ``a place of business under one management at one geographic 
location.'' The definition in proposed Sec.  207.1 also stated ``one 
geographic location may include separate buildings within the same city 
if their activities are closely related to the same business enterprise 
and are under the supervision of the same local management.''
    Rather than adopt this proposed definition, the final rule retains 
the definition of the term ``establishment'' that has appeared in the 
part 207 regulations since 1980. This definition states that an 
establishment is ``at one general physical location.''
    (Comment 7) One comment suggested that the phrase ``within the same 
city'' used in the proposed definition of ``establishment'' was too 
specific. This comment argued that a manufacturing facility located in 
a city with a warehouse located just outside that city should together 
be treated as a single establishment for registration purposes.
    (Response) In reviewing this comment and considering it in light of 
the longstanding definition of ``establishment'' and the objectives 
behind the establishment registration requirement, we determined that 
the existing definition in part 207 is clearer and better serves our 
objectives than would the proposed amended definition. The longstanding 
language, ``one general physical location,'' generally restricts a 
single establishment to one street address or one or more contiguous 
plots of land. We do not agree with the comment that a second facility 
located in a different city should be covered by the first facility's 
establishment registration.
    We note, however, that a facility operated only as a warehouse may 
not require registration. Section 510 of the FD&C Act and Sec.  207.17 
of this final rule

[[Page 60179]]

require registration of establishments where drugs are manufactured, 
repacked, relabeled, or salvaged. A facility at which drugs are merely 
stored may not require registration under this final rule, unless the 
facility includes, for example, controlled storage for stability 
testing as an element of good manufacturing practices. Other Federal 
and State requirements may apply to such facilities.
    Likewise, the corporate headquarters of a drug establishment should 
not register under this rule if drugs are not manufactured, repacked, 
relabeled, or salvaged at that location.
    d. Foreign. We proposed to use the term ``foreign'' to refer to a 
manufacturer, repacker, relabeler, drug product salvager, or private 
label distributor who is located in a foreign country and who 
manufactures, repacks, relabels, salvages, or distributes a drug that 
is imported or offered for import into the United States. When used to 
modify ``establishment,'' we proposed to use ``foreign'' to refer to an 
establishment that is located in a foreign country and is the site 
where a drug that is imported or offered for import into the United 
States was manufactured, repacked, relabeled, salvaged or distributed.
    We have omitted the words ``or distributed'' from this definition 
because only establishments at which drugs are manufactured, repacked, 
relabeled, or salvaged are required to be registered.
    (Comment 8) One comment urged us to revise the definition of 
``foreign'' to mean ``located in a foreign country'' while stating in 
Sec.  207.9 that part 207 applies to foreign entities who import or 
offer for import products into the United States.
    (Response) We do not agree that the proposed rule was confusing or 
difficult to understand in this respect and have decided against making 
this change.
    e. Importer. Section 207.25 of this final rule and section 510(i) 
of the FD&C Act require foreign establishments, when registering, to 
provide names and contact information for each importer in the United 
States of drugs manufactured, repacked, relabeled, or salvaged at the 
establishment that is known to the establishment. We proposed to define 
``importer'' to mean, in part, ``a company or individual in the United 
States that is an owner, consignee, or recipient of the foreign 
establishment's drug that is imported into the United States.'' In 
proposing this language, we recognized that a foreign establishment may 
have more than one importer, and we proposed to include in this term 
any owner, consignee, or recipient, even if not the initial owner, 
consignee, or recipient, of the foreign establishment's drug that is 
imported into the United States.
    (Comment 9) Some comments stated that our proposed definition of 
the term ``importer'' was too broad and would increase the burden on 
manufacturers to provide unnecessary information concerning a wide 
variety of entities that are not responsible for the drug. One comment 
noted that the inclusion of downstream recipients in our definition of 
``importer'' would impose a significant reporting burden on foreign 
establishments that is not required of domestic establishments.
    (Response) We agree that we should clarify and narrow the proposed 
definition of ``importer.'' As proposed, the definition included every 
U.S. recipient of a foreign-produced drug, excepting only the final 
consumer or patient. Of this large group, foreign establishments would 
be required to identify in their establishment registration submissions 
only those importers that are known to the establishment. To make this 
information element more useful to FDA and to reduce the burden on 
registered establishments, we have determined that in this context the 
term ``importer'' should include a U.S. owner, consignee, or recipient 
at the time of the drug's entry into the United States and should not 
include additional subsequent owners, consignees, or recipients of the 
drug. We have revised the definition of importer in Sec.  207.1 of the 
final rule accordingly.
    (Comment 10) One comment recommended that we change ``company or 
individual'' to ``person,'' in the rule's definition of ``importer,'' 
consistent with the definition of the term ``person'' in section 201(e) 
of the FD&C Act.
    (Response) We agree that the term ``person,'' as defined in the 
FD&C Act, is an improvement over ``company or individual'' in this 
definition. We have made this change in Sec. Sec.  207.1 and 607.3 of 
the final rule, and as discussed in our response to comment 6, we have 
also added a statement in Sec. Sec.  207.1(a) and 607.3(a) that the 
definitions and interpretations of terms in sections 201 and 510 of the 
FD&C Act apply if not otherwise defined.
    f. Person who imports or offers for import. Section 207.25 of this 
final rule and section 510(i) of the FD&C Act also require foreign 
establishments, when registering, to supply names and contact 
information for each person who imports or offers for import drugs 
manufactured, repacked, relabeled, or salvaged at the establishment. 
The proposed rule's definition of ``person who imports or offers for 
import'' included ``an agent, broker, or other entity, other than a 
carrier, that the foreign establishment uses to facilitate the import 
of its drug into the United States.'' We invited comments on the use 
and interpretation of the term ``facilitate.''
    (Comment 11) Some comments expressed concern regarding the 
potential breadth of this definition, noting in particular that the 
word ``facilitate'' could, in theory, encompass entities such as 
foreign insurance adjusters, underwriters, and international banks. 
Commenters pointed out the significant burden associated with the 
identification of such entities in foreign establishment registrations 
and updates to registrations, noting that international supply chains 
and business relationships are not static. One comment urged FDA to 
exclude customs brokers from the rule's definition of ``person who 
imports or offers for import.'' Another comment encouraged FDA to 
exclude middlemen from this definition, as their identities would 
change frequently.
    (Response) Although we did not intend for the word ``facilitate'' 
to be read as broadly as some comments suggested, FDA agrees that the 
definition of ``person who imports or offers for import'' should be 
made more precise, narrow, and useful.
    We note, as a matter of clarification, that in section 510(i) of 
the FD&C Act and in Sec.  207.25 of the final rule, the requirement 
that foreign establishments identify each person who imports or offers 
for import is not said to be limited to persons known to the 
establishment (unlike the requirement that they identify 
``importers''). The preamble to the proposed rule included statements 
that were inconsistent with the FD&C Act in this regard, suggesting 
that foreign establishments would be required to report the name of 
each person known to the establishment who imports or offers for import 
its drug(s) into the United States. See, e.g., 71 FR 51276 at 51289. In 
fact, the proposed rule (proposed Sec.  207.25), the final rule, and 
the FD&C Act all require foreign establishments to report, when 
registering, the name of each person who imports or offers for import 
its drug(s) into the United States without regard to whether such 
persons are known to the establishment. Therefore, it is important that 
we define ``person who imports or offers for import'' in a way that is 
practical, useful, and consistent with this understanding.

[[Page 60180]]

    Our intention in defining this term is to include foreign persons 
who are primarily responsible for sending a drug to the United States. 
Foreign establishments are reasonably expected to know the identities 
of such persons. In many cases, the establishment itself will be a 
person who imports or offers for import its drugs into the United 
States. In other cases, it will be a person the foreign establishment 
engages to send one or more drugs to the United States. It will 
generally be the foreign person who owns the drug and sells or enters 
into a contractual obligation to supply the drug to a person in the 
United States.
    In light of the comments received and FDA's objectives, the final 
rule defines ``person who imports or offers for import'' to mean the 
owner or exporter of a drug who consigns and ships a drug from a 
foreign country to the United States. This definition includes persons 
who send a drug to the United States by international mail or other 
private delivery service, but does not include carriers who merely 
transport the drug. This definition is not intended to include persons 
operating merely as customs brokers.
    g. Manufacture, manufacturer. The definitions of ``manufacture'' 
and ``manufacturer'' in Sec.  207.1 of this final rule include minor 
editorial revisions for clarity and new references to animal feed 
bearing or containing a new animal drug.
    (Comment 12) Some comments stated that the definition of 
``manufacturer'' should specify that it applies only to entities 
manufacturing drugs for commercial distribution.
    (Response) We disagree with the recommendation that the definition 
of ``manufacturer'' be limited to drugs manufactured ``for commercial 
distribution.'' The underlying statutory provisions require 
registration of establishments where drugs are manufactured, without 
regard to commercial distribution (section 510(c) of the FD&C Act), but 
require listing of drugs that are manufactured for commercial 
distribution (section 510(j) of the FD&C Act). Accordingly, under Sec.  
207.17 of this final rule, each domestic establishment where a drug is 
manufactured (or repacked, relabeled, or salvaged) must be registered 
unless exempt from registration under section 510(g) of the FD&C Act or 
under Sec.  207.13, regardless of whether the drug is commercially 
distributed. The drug listing obligation, as described in Sec.  207.41, 
applies to drugs that are manufactured, repacked, relabeled, or 
salvaged for commercial distribution. (See separate definition of 
``commercial distribution.'')
    (Comment 13) One comment asked that drug sponsors be included in 
the definition of manufacturer. Other comments suggested that FDA add 
``product formulator'' to the definition of ``manufacturer'' or provide 
definitions for terms such as ``drug sponsor.'' These comments pointed 
out that the holder of an approved application, such as an NDA, or the 
formulator of a nonprescription monograph product may use a contract 
manufacturer to produce the product for distribution under the name of 
the application holder or the product formulator. Some comments 
recommended that the final rule treat such application holders or 
product formulators as manufacturers so they would register their 
establishments and list such products and that it exempt contract 
manufacturers from the drug listing requirement.
    (Response) We decline to add the application holder or ``product 
formulator'' concepts to the definition of ``manufacturer.'' Under 
section 510(c) of the FD&C Act, the obligation to register drug 
establishments rests on owners or operators of establishments engaged 
in the manufacture (including repacking, relabeling, and salvaging) of 
drugs, and the listing obligation applies to ``every person who 
registers.'' FDA recognizes that this language could be read broadly to 
encompass entities that develop or formulate drug products without 
performing manufacturing operations. However, considering the 
objectives behind drug registration and listing, we are currently 
interested in the registration of establishments where manufacturing 
operations (including repacking, relabeling, and salvaging) take place 
and the listing of drugs handled at those establishments.
    We recognize, however, that an application holder or a product 
formulator using a contract manufacturer to manufacture a drug may wish 
to submit drug listing information for that product directly to FDA. 
Although the actual manufacturer of the drug has the legal obligation 
to list it, FDA would accept listing information for the drug submitted 
by its formulator or any other person acting as an authorized agent for 
the manufacturer. When we use the term ``authorized agent'' in this 
final rule, we mean a person who is authorized to act on behalf of 
another. The term ``authorized agent'' should not be confused with the 
United States agent referred to in Sec.  207.69(b).
    (Comment 14) Several comments asked for clarification on how the 
terms ``manufacture,'' ``repackage,'' ``relabel'' and ``private label 
distributor'' would apply to the medical gas industry and pointed out 
that certain medical gas operations, such as the transfilling of gas 
from one container to another, have long been treated as drug 
manufacturing by FDA but, under the proposed rule, would seem to 
qualify as ``repacking.'' These comments asked FDA to classify medical 
gas refillers as ``manufacturers'' rather than ``repackers'' in the 
final rule.
    (Response) FDA agrees that these important points require 
clarification. Nothing in this final rule is intended to alter the 
definitions applicable to FDA's regulations governing current good 
manufacturing practices for drug products, parts 210 and 211. 
Therefore, the definition of ``manufacture, processing, packing, or 
holding of a drug product'' currently appearing in Sec.  210.3(b)(12) 
will continue to apply to medical gases as that definition has always 
applied.
    For purposes of part 207, we will interpret the definition of 
``manufacture'' in Sec.  207.1 as including the initial manufacturing 
process that produces or purifies a medical gas, whether by air 
separation, chemical reaction, or other process. Additionally, the 
mixing of two or more medical gases to produce a combination would also 
qualify as ``manufacture'' under Sec.  207.1. The impact of this 
interpretation is that a person who thus qualifies as a manufacturer of 
a medical gas will be required to submit the drug listing information 
required under Sec.  207.49 of this final rule (``What listing 
information must a registrant submit for a drug it manufactures?'') in 
addition to registering the establishment(s) at which manufacturing is 
conducted.
    All subsequent transfillings of a medical gas from one container to 
another (i.e., from tanker trucks into standing tanks and from standing 
tanks into smaller containers, etc.) would fall within the definition 
of ``repack or repackage'' in Sec.  207.1 of this final rule. The 
impact of this interpretation is that a person who thus qualifies as a 
repacker of a medical gas will be required to submit the drug listing 
information required under Sec.  207.53 of this final rule (``What 
information must a registrant submit for a drug that it repacks or 
relabels?'') in addition to registering the establishment(s) at which 
repackaging is conducted. Comments opposing this classification 
expressed concern that under the proposed rule, repackers would be 
required to identify the NDC assigned to a drug immediately before it 
is received by the repacker as information that must be submitted to 
obtain an NDC for a repackaged drug

[[Page 60181]]

under proposed Sec.  207.33(d)(1)(ii). See our response to Comment 73 
regarding an exemption for medical gases from the requirement that 
registrants submit such source NDCs for drugs they repackage or 
relabel.
    The definition of ``relabel'' in Sec.  207.1 of this final rule 
applies to medical gases. It refers to changing or altering the 
existing label on a drug or drug package, without repacking the drug or 
drug package. A person who places a label on a repackaged drug (e.g., a 
medical gas recently filled into a canister) for the first time 
qualifies as a ``repackager'' as that term is defined in this final 
rule.
    The term ``private label distributor'' is defined in Sec.  207.1 of 
this final rule to mean, with respect to a particular drug, a person 
who did not manufacture, repack, relabel, or salvage the drug but under 
whose label or trade name the drug is commercially distributed. This 
definition applies equally to private label distributors of medical 
gases and other drugs. A medical gas transfiller is a repackager, and 
not a private label distributor, under this final rule. As discussed in 
our response to comment 16, private label distributors do not--by 
reason of their status as private label distributors--have an 
obligation to register establishments or list drugs. They must have 
labeler codes, obtained under new Sec.  207.33(c), and they may submit 
drug listing information or establishment registration information if 
acting as the authorized agent of a registrant on whose behalf the 
information is submitted.
    h. Material change. In the proposed rule, ``material change'' was 
defined as any change in any drug listing information, excluding 
labeling changes in arrangement or printing or labeling changes of an 
editorial nature. This definition is retained in the final rule with 
minor revisions to clarify that material change also does not include 
changes in the format of labeling, or the inclusion of a bar code or 
the initial inclusion of an NDC on a label.
    (Comment 15) One comment asked FDA to clarify the types of labeling 
changes that would qualify as a material change and, hence, require 
reporting as an update to drug listing information under Sec.  207.57. 
This comment specifically suggested examples of labeling changes that 
would qualify as significant changes in the labeling of a prescription 
drug product or significant changes in the label or package insert of 
an OTC drug product.
    (Response) In referring to ``significant'' labeling changes, this 
comment seems to relate to the longstanding definition of ``material 
change'' in Sec.  207.3(a)(3), prior to this final rule, which 
encompassed labeling changes described as ``significant.'' Today's 
final rule revises that definition so that material change includes any 
labeling change other than changes in the format of labeling, changes 
of an editorial nature, inclusion of a bar code, or initial inclusion 
of an NDC. In this context, changes of an editorial nature would not 
include any changes that add or revise meaning.
    Thus, the new definition of ``material change'' adopted as part of 
this final rule is broader than the previous definition and is not 
limited to ``significant'' changes. The definition includes--with very 
few exceptions--any change in previously reported drug listing 
information. FDA intends to rely primarily on new Sec.  207.57 to 
maintain an up-to-date database of current drug labeling. Registrants 
should submit current labeling (and a resubmission of all listing 
information) each time they submit a drug listing update to report 
changed information under Sec.  207.57.
    i. Private label distributor. We proposed to define ``private label 
distributor'' to mean a person who owns or operates an establishment 
that commercially distributes, under its own label or trade name, any 
drug manufactured, repacked, relabeled, or salvaged by a registered 
establishment. In the preamble to the proposed rule we explained that 
the private label distributor does not engage in any activities 
performed by a manufacturer, repacker, relabeler, or salvager for the 
drug it distributes (71 FR 51276 at 51290).
    In the final rule, private label distributor is defined to mean, 
with respect to a particular drug, a person who did not manufacture, 
repack, relabel, or salvage the drug but under whose label or trade 
name the drug is commercially distributed. We have also defined 
``private label distribution'' in this final rule to mean commercial 
distribution of a drug under the label or trade name of a person who 
did not manufacture, repack, relabel, or salvage that drug.
    (Comment 16) Some comments requested clarification regarding the 
distinction between private label distributors, manufacturers, and 
wholesale distributors. Others urged FDA to allow private label 
distributors to list the drugs they distribute. One comment requested 
clarification regarding the responsibilities of private label 
distributors under part 207.
    (Response) We agree that more clarity is needed regarding these 
terms and the registration and listing obligations associated with 
private label distribution of drug products. We have eliminated the 
mention of establishment ownership in the proposed rule's definition of 
``private label distributor'' because private label distributors do not 
necessarily own establishments that require registration under section 
510 of the FD&C Act. We have also clarified that an entity may act as a 
private label distributor with respect to a particular drug. For 
example, if a drug manufacturer distributes, under its own name or 
trade name, a drug manufactured entirely by a contract manufacturer, it 
is acting as a private label distributor with respect to that drug. The 
difference between private label distributors and wholesale 
distributors or others involved in drug distribution is that a private 
label distributor's name, trade name, or label appears on the product. 
A common example of private label distribution is the sale of aspirin 
under a retail pharmacy's brand name when the retail pharmacy did not 
manufacture the product. As defined in this final rule, private label 
distribution encompasses the use of any brand name or business name on 
a drug product where the named business or the owner of the brand name 
did not manufacture the drug. Thus, as we are defining the term in part 
207, a private label distributor may, but does not necessarily, operate 
retail stores or play a role in the physical distribution of the drug 
product. Even without using a brand name, if an entity is identified as 
the distributor or marketer of a drug under Sec.  201.1 of the drug 
labeling regulations, without having manufactured the drug, that person 
will qualify as a private label distributor as the term is defined in 
this final rule.
    Under this final rule, private label distributors do not have 
registration or listing obligations with respect to drugs for which 
they merely act as private label distributors. Only manufacturers, 
repackers, relabelers, and salvagers have an obligation to register and 
list. Private label distributors are subject to this final rule only in 
that they must apply for an NDC labeler code as described in Sec.  
207.33(c) and update the information submitted under that section when 
the information changes. Private label distributors are in the best 
position to obtain their own labeler codes and update information 
associated with those codes, thereby preventing potential submissions 
of inconsistent or inaccurate information by multiple contract 
manufacturers.
    A person who is a private label distributor with respect to a 
particular drug does not for that reason incur an establishment 
registration or listing

[[Page 60182]]

obligation. The FD&C Act and the regulations in part 207 both place the 
registration and listing obligation on persons who manufacture, repack, 
relabel, or salvage drugs. The registration and listing obligation thus 
rests with the actual manufacturer, repacker, relabeler, or salvager 
whether or not a product is intended for private label distribution. 
For this reason, the final rule does not include provisions regarding 
establishment registrations or drug listings submitted by private label 
distributors.
    We recognize, however, that some private label distributors are in 
a position to supply listing information, including NDCs, for drugs 
distributed under their names and may prefer to do so. FDA will accept 
registration and listing information submitted by any authorized agent 
acting on behalf of a manufacturer, repacker, relabeler, or salvager, 
and this includes a private label distributor authorized by a 
manufacturer, repacker, relabeler, or salvager, to submit drug listing 
information on its behalf. In these cases, the manufacturer, repacker, 
relabeler, or salvager remains responsible for compliance with all 
registration and listing requirements and the accuracy of the 
information submitted by its agent.
    A person who acts merely as a wholesale distributor of a drug 
product (i.e, a person who did not manufacture, repack, relabel, or 
salvage the drug product and whose name, trade name, or label does not 
appear on the drug product) does not incur obligations under this rule.
    j. Relabel, relabeler, repack, repacker. We proposed to define 
``relabel'' to mean changing the label or labels on a drug or drug 
package, or adding to the labeling for a drug or drug package, without 
repacking the drug or drug package. We also proposed to define 
``relabeler'' to mean a person who owns or operates an establishment 
that relabels a drug.
    We proposed to define ``repack'' to mean repack or repackage or 
otherwise change the container or wrapper of a drug or drug package. 
Similarly, we proposed to define ``repacker'' to mean a person who owns 
or operates an establishment that repacks a drug or drug package.
    In the final rule, these definitions are clarified and revised in 
response to comments.
    (Comment 17) Some comments noted that the definition of relabel 
could include wholesale drug distributors who add information to outer 
container labels for purposes of delivery to a customer, customer 
identification, inventory management, special handling instructions, or 
to aid in compliance with Federal and State pedigree requirements. 
Commenters urged us not to require establishments (e.g., distribution 
facilities) where such relabeling occurs to register and list.
    (Response) We agree generally with these comments and have revised 
the definition of ``relabel'' in the final rule to exclude the addition 
or modification of information affixed solely for purposes of delivery 
to a customer, customer identification, or inventory management. 
However, we did not exclude the addition of special handling 
instructions from the definition of ``relabel,'' as recommended in 
these comments. Such an exclusion might be misinterpreted as 
accommodating revised storage instructions in drug labeling. However, 
FDA would not object to the addition of storage information to an outer 
label if such information is not inconsistent in any way with storage 
instructions appearing elsewhere in the drug's labeling. In that case, 
FDA would not regard the addition of such storage information to an 
outer container label as relabeling that would subject a person to 
registration and listing.
    k. Representative sampling of advertisements and Representative 
sampling of any other labeling. The definitions of these terms included 
in the proposed rule appear in this final rule with one minor revision.
    (Comment 18) The preamble to the proposed rule included a brief 
discussion of these definitions. That discussion pointed out a 
confusing aspect of the previous definitions of these terms and the 
previous definition of the term ``advertising and labeling'' in part 
207. See 71 FR 51276 at 51291. One comment argued that there was no 
conflict in these definitions and urged FDA to retain our previous 
definitions of ``representative sampling of advertisements'' and 
``representative sampling of any other labeling.'' This comment pointed 
out that the examples given in those previous definitions were helpful.
    (Response) We disagree with this comment. The revised definitions 
are intended to eliminate some confusion associated with the previous 
definitions as explained in the preamble to the proposed rule. The 
examples appearing in the previous definitions read as follows: ``If 
more than one medical journal advertisement is used but the promotional 
content is essentially identical, only one need be submitted'' and ``if 
more than one brochure is used but the promotional content is 
essentially identical, only one need be submitted.'' The quoted 
language served as common sense guidance regarding the application of 
the definitions without being a central part of the definitions. 
Although omitting that language from the definitions included in the 
proposed rule and this final rule, FDA is not disavowing the examples 
or suggesting that registrants should take a different approach.
2. Who does this part cover? (Sec.  207.9)
    The Agency proposed new Sec.  207.9 to clarify the types of 
businesses that are subject to drug establishment registration and 
listing under part 207. Section 207.9 is retained in this final rule 
with certain revisions and clarifications.
    Section 207.9(a)(3) of this final rule clarifies that private label 
distributors are subject to part 207. As discussed previously in this 
document, private label distributors do not have an obligation to 
register an establishment or list any drugs arising from their 
activities as private label distributors. They are, however, expected 
to obtain NDC labeler codes under Sec.  207.33(c) of this final rule 
and update the information reported to FDA under Sec.  207.33(c) as 
required by Sec.  207.33(c)(2).
    Section 207.9(a)(4) of this final rule is revised to state more 
clearly its applicability to establishments engaged in the manufacture, 
repacking, relabeling, or salvaging of drugs regulated under a BLA. 
These establishments are subject to part 207 unless they are required 
to register and list under part 607 (ESTABLISHMENT REGISTRATION AND 
PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS).
    Section 207.9(a)(5) of this final rule is revised to state that 
HCT/Ps, as defined in Sec.  1271.3(d), are subject to registration and 
listing under part 207 if they are drugs regulated under section 505 of 
the FD&C Act or under section 351 of the PHS Act. A conforming 
amendment is made to Sec.  1271.1. Manufacturers of HCT/Ps that are 
regulated under section 361 of the PHS Act (42 U.S.C. 264) and not 
under section 351 will remain subject to registration and listing under 
part 1271.
    (Comment 19) Comments requested clarification on the applicability 
of this rule to contract manufacturers and private label distributors 
of drug products, saying it was not clear in the proposed rule how 
contract manufacturers are to handle establishment registration and 
labeler code assignment.
    (Response) Manufacturers of drug products are obligated by the FD&C 
Act and by this final rule--whether or not

[[Page 60183]]

they are contract manufacturers--to register their establishments and 
list the drugs they manufacture for commercial distribution (as the 
term ``commercial distribution'' is defined in new Sec.  207.1). 
Sections 207.49 and 207.53 of this final rule require manufacturers, 
repackers, and relabelers to provide their own NDC (an NDC that 
includes the registrant's own labeler code) for each drug they list. 
(Salvagers are not required to provide new NDCs when listing drugs they 
salvage because a drug's NDC does not change when it is merely 
salvaged, and not repacked or relabeled. A person who salvages and then 
repacks or relabels a drug is a repacker or relabeler, as those terms 
are defined in Sec.  207.1, and must register and list as a repacker or 
relabeler.) This provision requires manufacturers, repackers, and 
relabelers responsible for listing drugs, including contract 
manufacturers, to obtain an NDC labeler code in accordance with new 
Sec.  207.33(c).
    When listing a human drug manufactured for private label 
distribution (distribution under the name or trade name of someone 
other than the drug's manufacturer, as defined in new Sec.  207.1), 
Sec. Sec.  207.49 and 207.53 require registrants to provide two NDCs, 
one that includes the registrant's own NDC labeler code and one that 
includes the NDC labeler code of the private label distributor. As 
stated in response to comment 16, FDA will accept drug listing 
information submitted by a private label distributor (or anyone else) 
if properly authorized to act as an agent for the actual manufacturer. 
The use of an agent to handle establishment registration or drug 
listing submissions does not, however, transfer legal responsibility 
for complying with this final rule from a manufacturer, repacker, 
relabeler, or salvager to its agent. Animal drugs manufactured for 
private label distribution should be listed under a single NDC that 
includes the labeler code of the private label distributor.
    Note that the term ``private label distributor'' is defined in new 
Sec.  207.1 to mean, with respect to a particular drug, a person who 
did not manufacture, repack, relabel, or salvage the drug but under 
whose label or trade name the drug is commercially distributed. FDA's 
statements in this document that private label distributors are not 
obligated to register their establishments or list the drugs they 
distribute are premised on this definition. If someone who would 
otherwise qualify as a private label distributor carries out testing or 
control procedures applied to the final product, e.g., systematic batch 
release testing required under current good manufacturing practices, 
that person may qualify as a manufacturer (see the definition of 
``manufacture'' in new Sec.  207.1) and need to register its 
establishment where the testing or control procedures are carried out. 
(But if a private label distributor uses a contract laboratory to carry 
out the testing or control procedures, the contract laboratory, not the 
private label distributor, may qualify as a manufacturer and need to 
register its establishment.) Likewise, if someone qualifies as a 
private label distributor with respect to one or more drugs, but also 
qualifies as a manufacturer, repacker, or relabeler with respect to 
other drugs, that person would need to register the establishment where 
manufacturing, repacking, or relabeling is conducted and list the drugs 
that are manufactured, repacked, or relabeled for commercial 
distribution at the registered establishment.
    Entities that qualify as private label distributors under this 
final rule and do not also manufacture, repack, relabel, or salvage any 
drugs may already have effective establishment registrations and drug 
listings submitted in the past. We do not expect these entities to 
renew their registrations after the effective date of this final rule. 
They may either cancel their registrations or allow their registrations 
to lapse by not making any further submissions. Any drug listings 
submitted in the past by entities that qualify as private label 
distributors under this final rule for drugs they do not manufacture, 
repack, relabel, or salvage should be transferred to the actual 
manufacturers, repackers, relabelers, or salvagers of the listed drugs.
    (Comment 20) One comment asked FDA to clarify whether radiologic 
products are subject to this rule.
    (Response) This comment did not elaborate on the types of products 
encompassed by the question so we are unable to respond specifically. 
There is not an exemption from the establishment registration and drug 
listing requirements for manufacturers of radioactive drugs, also known 
as radiopharmaceutical products. Anyone with questions about the 
applicability of part 207, either before or after this final rule, to 
radioactive drug products should contact the electronic Drug 
Registration and Listing System staff in the Office of Compliance at 
FDA's Center for Drug Evaluation and Research (CDER). For diagnostic 
device products that include a radioactive drug constituent part, see 
our response to comment 22 in this document regarding drug/device 
combination products. Also see part 807 regarding establishment 
registration and listing for radiologic device products. Positron 
emission tomography (PET) drugs are subject to part 207, as stated in 
Sec.  207.13(l)(1) and as discussed in the proposed rule (71 FR 51276 
at 51285).
    (Comment 21) One comment requested guidance regarding the 
information needed for ``active drug substance manufacturers'' to 
register and list.
    (Response) In this final rule, the term ``active pharmaceutical 
ingredient'' (API) is defined in Sec.  207.1. The registration 
obligation applies to each domestic establishment that manufacturers, 
repacks, relabels, or salvages a drug or an animal feed bearing or 
containing a new animal drug (whether or not that product is 
commercially distributed). It also applies to each foreign 
establishment that manufacturers, repacks, relabels, or salvages a drug 
or an animal feed bearing or containing a new animal drug that is 
imported or offered for import into the United States. In each case, 
the term ``drug'' includes: (1) An API by itself, (2) an API that has 
been combined with one or more other APIs or inactive ingredients (see 
definition of ``unfinished drug'' in Sec.  207.1), and (3) finished 
drug products (see definition of ``finished drug product'' in Sec.  
207.1).
    The information that must be submitted for establishment 
registration is set forth in new Sec.  207.25. These information 
elements do not differ depending on whether the registrant handles 
APIs, other unfinished drugs, or finished drugs.
    The information that must be submitted with a drug listing is set 
forth in new Sec.  207.49 for a drug the registrant manufactures, Sec.  
207.53 for a drug the registrant repacks or relabels, and in Sec.  
207.54 for a drug the registrant salvages. As specified in Sec.  
207.41, the drug listing obligation applies only to drugs that are 
manufactured, repacked, relabeled, or salvaged for commercial 
distribution. Sections 207.49, 207.53, and 207.54 indicate some minor 
differences in the information that must be submitted depending on 
whether the drug is finished or unfinished. For example, Sec.  
207.49(a)(15)(iv) describes the labeling that must be submitted for an 
unfinished drug.
    (Comment 22) One comment asked, in the context of the proposed 
rule's requirement that NDCs appear on drug labels, how the rule would 
apply to drug/device combination products. Other comments asked how 
registration and listing should be handled for drug/device combination 
product kits. (See the definition of ``combination product'' in Sec.  
3.2(e) (21 CFR 3.2(e)), unaffected by this rulemaking.)

[[Page 60184]]

    (Response) We acknowledge that the proposed rule did not include an 
explanation of its applicability to drug/device combination products, 
including how manufacturers of such products should register their 
establishments, list their combination products, and provide related 
information on the labels of their combination products. The codified 
of this final rule likewise does not contain specific provisions 
regarding drug/device combination products. FDA expects to further 
address drug/device combination product registration and listing in the 
future. As stated previously in this document, we also are not 
finalizing the proposed amendment to Sec.  201.2 that would have 
required human-readable NDCs on the labels of all drugs subject to the 
listing requirement.
3. Who is exempt from registration and listing requirements? (Sec.  
207.13)
    The proposed rule included a new Sec.  207.13 aimed at clarifying 
the types of businesses that are exempt from drug establishment 
registration and listing under part 207. Section 207.13 is retained in 
this final rule with certain revisions and clarifications. Some 
exemptions described in Sec.  207.13 are derived directly from section 
510(g) of the FD&C Act. Other exemptions are established under section 
510(g)(5) of the FD&C Act supported by our finding that registration by 
such classes of persons is not necessary for the protection of the 
public health.
    (Comment 23) Several comments argued against the elimination of two 
existing exemptions from registration and listing that the proposed 
rule would have revoked. These two exemptions encompass: (1) Drugs 
imported under section 801(d)(3) of the FD&C Act (often referred to as 
``import for export'') and (2) drugs that enter a foreign trade zone 
and are re-exported from that foreign trade zone without having entered 
U.S. commerce.
    (Response) Previous Sec.  207.40(b) stated that no drug may be 
imported or offered for import into the United States unless the drug 
is listed and manufactured, prepared, propagated, compounded, or 
processed at a registered foreign establishment. The section also 
stated that this prohibition did not apply to, among other things, 
components of drugs imported under section 801(d)(3) of the FD&C Act. 
Section 801(d)(3) allows persons to import certain articles, including 
components of drugs, if specified conditions are met, provided that the 
imported articles are further processed or incorporated into products 
and exported or, if not used, the imported articles are destroyed or 
exported. Thus, previous Sec.  207.40(b) exempted certain foreign 
establishments from the establishment registration and listing 
requirement.
    Previous Sec.  207.40(a) stated that a foreign establishment was 
not required to comply with the registration and listing requirements 
if its drug entered a foreign trade zone and was re-exported from that 
foreign trade zone without having entered U.S. commerce.
    Upon careful consideration of the comments received, we have 
decided to retain both exemptions in this final rule. Therefore, under 
Sec.  207.13(j) of this final rule, if all the conditions of section 
801(d)(3) of the FD&C Act are satisfied, a component of a drug will not 
be excluded from importation into the United States by reason that it 
is unlisted or was manufactured at an unregistered foreign 
establishment. Additionally, under Sec.  207.13(j) of this final rule, 
a foreign establishment does not incur a registration and listing 
obligation if its drug enters a foreign trade zone and is re-exported 
from that foreign trade zone without having entered U.S. commerce. 
These exemptions pertain only to drugs that are re-exported or 
components of drugs that are processed or incorporated into products 
and then exported, and these exemptions pertain only to foreign 
establishments. If an establishment located within a foreign trade zone 
manufactures, repacks, relabels, or salvages a drug for commercial 
distribution in the United States, that establishment would need to 
register and list those drugs it handles for U.S. commercial 
distribution. Additionally, if a foreign establishment exports drugs to 
the United States relying on either of these exemptions, but also 
exports other drugs for commercial distribution in the United States, 
it must comply with the registration and listing requirements for those 
drugs that are commercially distributed in the United States.
    The corresponding exemptions for blood product establishments are 
also retained in Sec.  607.40 under this final rule.
    (Comment 24) One comment asked FDA to confirm that animal 
biological products are not subject to this rule.
    (Response) Some biological drugs intended for administration to 
animals are regulated by the U.S. Department of Agriculture (USDA) 
under the Virus, Serum, and Toxins Act of 1913. Section 510.4 (21 CFR 
510.4) states that animal drugs produced and distributed in full 
conformance with the Virus, Serum, and Toxins Act and any regulations 
issued thereunder shall not be deemed to be subject to section 512 of 
the FD&C Act (includes premarket approval and other requirements for 
new animal drugs regulated by FDA). As proposed in Sec.  207.13(g), the 
final rule includes an exemption applicable to these products in Sec.  
207.13(h).
    (Comment 25) Comments from the medical gas industry expressed 
concern about the ability of entities such as pharmacies, hospitals, 
clinics, and emergency responders to refill medical gas cylinders if 
the repackaging would require the repacker's NDC to appear on the label 
of the repackaged product. The comment stated that if these entities 
are exempt from part 207, they cannot obtain an NDC.
    (Response) Our decision not to include the proposed amendments to 
Sec.  201.2 that would have required human-readable NDCs on drug labels 
renders the concern expressed in this comment moot. We would like to 
confirm that pharmacies, hospitals, clinics, other health care 
entities, and public health agencies that qualify as exempt from the 
registration and listing requirements under Sec.  207.13 of this final 
rule do not lose their exemptions by dispensing medical gases or 
filling medical gas containers in the normal course of their 
activities.

C. Registration (Part 207, Subpart B)

1. Who must register? (Sec.  207.17)
    Section 207.17 describes who is required to register an 
establishment under part 207. This section is reworded in the final 
rule: (1) To distinguish between domestic and foreign manufacturers, 
repackers, relabelers, and salvagers and (2) to clarify that FDA will 
accept registration information submitted by a private label 
distributor only if it is acting as an authorized agent for and 
submitting information pertaining to an entity that has an 
establishment registration obligation.
    (Comment 26) One comment asked FDA to clarify whether a storage 
facility that does not repack or relabel drugs is required to register 
under part 207.
    (Response) A facility at which drugs are stored, such as a 
warehouse, does not need to be registered provided drugs are not 
manufactured, repacked, relabeled, or salvaged (as those terms are 
defined in Sec.  207.1) at the facility. Note that the definition of 
``manufacture'' includes sampling, testing, or control procedures 
applied to the final product or to any part of the process. Thus, for 
example, if a warehouse includes a temperature-controlled storage area 
where drug samples are stored for stability testing to satisfy current 
good manufacturing practice requirements, that activity would qualify 
as a manufacturing

[[Page 60185]]

operation and require registration of the warehouse as a drug 
establishment. Other State or Federal requirements may apply to such 
facilities.
    As explained in response to Comment 17, we have revised the 
definitions of ``relabel'' and ``relabeler'' so they do not include the 
addition or modification of information affixed to drug packaging 
solely for purposes of delivery to a customer, customer identification, 
or inventory management. Therefore, the addition or modification of 
such information at a warehouse does not trigger the need to register 
it as an establishment.

2. When must initial registration information be provided? (Sec.  
207.21)

    Proposed Sec.  207.21 described when initial registration 
information must be submitted for an establishment newly required to 
register under part 207. The provision is retained in this final rule 
and reorganized into paragraphs (a) and (b) for improved clarity.
    (Comment 27) One comment suggested that the words ``for commercial 
distribution'' be added to Sec.  207.21, suggesting that establishment 
registration is required only for establishments at which drugs 
intended for commercial distribution are manufactured, repacked, 
relabeled, or salvaged.
    (Response) The absence of these words--``for commercial 
distribution''--from Sec.  207.21 is intentional and comports with 
section 510 of the FD&C Act. Any establishment at which drugs are 
manufactured, repacked, relabeled, or salvaged must be registered under 
part 207, unless exempt from registration under section 510(g) of the 
FD&C Act or under the relevant regulations (Sec. Sec.  207.13, 607.65, 
or 1271.15, as applicable) whether or not the drugs are commercially 
distributed. Accordingly, an establishment at which an investigational 
drug is manufactured is subject to the establishment registration 
requirement. The listing obligation, on the other hand, applies to 
drugs that are for commercial distribution.
3. What information is required for registration? (Sec.  207.25)
    Proposed Sec.  207.25 described the information that must be 
submitted to register an establishment. The provision is retained in 
the final rule with minor substantive and editorial revisions. 
Substantively, new Sec.  207.25 no longer requires the submission of 
fax numbers to register establishments and now includes the new 
statutory requirement that registrants provide a UFI for each 
establishment. (See our discussion of establishment registration 
numbers and UFIs in section II.B, Changes to the Proposed Rule.) New 
Sec.  207.25 also clarifies that the physical address of each 
establishment is required (rather than a post office box, for example), 
and a mailing address is required for the establishment's official 
contact.
    (Comment 28) One comment asked FDA to clarify what format should be 
used when a foreign establishment submits contact information for each 
importer. This comment also asked FDA to explain who should submit 
establishment registration information when a business has both foreign 
and U.S. establishments.
    (Response) According to new Sec.  207.61, all information 
transmitted to FDA under part 207, including establishment registration 
information, must be transmitted to FDA in electronic format unless a 
waiver is granted. FDA's systems for electronic registration include 
fields for information elements such as the required contact 
information for U.S. importers of drugs manufactured, repacked, 
relabeled, or salvaged at a foreign establishment.
    Section 207.17 addresses this comment's second question, who should 
submit establishment registration information when a business has both 
foreign and U.S. establishments? This section states that when 
operations are conducted at more than one establishment, and common 
ownership and control among all the establishments exists, the parent, 
subsidiary, or affiliate company may submit registration information 
for all establishments. This applies whether the establishments are 
domestic, foreign, or both.
    (Comment 29) One comment asked FDA to exempt contract manufacturers 
from the requirement that establishments identify each importer in the 
United States of drugs they manufacture, repack, relabel, or salvage 
that is known to the establishment as well as each person who imports 
or offers for import such drugs to the United States. This comment 
stated that contract manufactures may not have this information.
    (Response) This requirement is retained in the final rule, in Sec.  
207.25(h). The provision implements a statutory requirement (section 
510(i)(1) of the FD&C Act). This requirement pertains only to foreign 
establishments, and it requires them to identify ``importers'' known to 
the establishment and ``persons who import or offer for import,'' as 
these terms are defined in Sec.  207.1. Both of these definitions have 
been refined and narrowed in this final rule. A foreign contract 
manufacturer exporting drugs to the United States should be able to 
identify such persons.
4. What are the requirements for reviewing and updating registration 
information? (Sec.  207.29)
    Section 207.29 describes the requirements for: (1) Expedited 
updating of certain changes to establishment registration information 
and (2) annual reviewing and updating of establishment registration. 
This section is retained in the final rule with very minor revisions. 
Fax numbers are no longer mentioned in Sec.  207.29(a) because they are 
no longer required for establishment registration. Additionally, the 
dates during which the annual review and update of registration 
information must take place have been adjusted to match section 
510(b)(2) of the FD&C Act, added by FDAAA.
    (Comment 30) Some comments opposed the requirement that if no 
changes have occurred since the last registration, registrants certify 
that no changes have occurred.
    (Response) The annual review and updating of establishment 
registration information is critical to the integrity of FDA's 
database. The requirement that registrants certify that no changes have 
occurred when that is true provides important assurance that 
registrants have reviewed the establishment registration information 
they previously submitted. Otherwise, FDA would need to interpret 
silence from a registrant as indicating either that the information 
remains up to date or that the registrant may have neglected to review 
and update the information. We further note that section 510(b)(1) of 
the FD&C Act now requires annual registration of establishments between 
October 1 and December 31, and the option to certify that no changes 
have occurred since the last registration is a minimally burdensome 
implementation of this statutory requirement.
    Please see our response to Comment 74, which addresses this issue 
in the context of drug listing updates.

D. National Drug Code (Part 207, Subpart C)

1. What is the national drug code (NDC), how is it assigned, and what 
are its requirements? (Sec.  207.33)
    The NDC provisions in this final rule have been revised in response 
to comments received on the proposed rule. Most significantly, new 
Sec.  207.33:
     Allows for 11 digits in the NDC (when 10-digit 
combinations are exhausted).
     Reflects that registrants will propose their own NDCs for 
drugs they

[[Page 60186]]

list. Under the proposed rule, FDA would have assigned NDCs in response 
to submissions from registrants. Under this final rule, each registrant 
must propose its own NDC for each drug the registrant lists. FDA will 
assign the proposed NDCs to the listed drugs unless they are improperly 
formatted, previously assigned to a listed drug, or reserved.
     Includes new NDC formatting requirements for registrants 
to observe when proposing NDCs.
     Transfers some information that would have been required 
under proposed Sec.  207.33(c) (What information must a manufacturer 
submit before we will assign an NDC number to a drug?) to information 
that must be included in a drug listing submission.
     Allows certain drug products to be assigned alternatively 
formatted NDCs if approved by the Center Director. This applies to the 
HCT/Ps specified in new Sec.  207.33(b)(4) if they are minimally 
manipulated.
     Includes a new Sec.  207.33(c) that explains who must 
obtain an NDC labeler code and how labeler codes are assigned and 
updated.
     Includes new provisions in Sec.  207.33(d) that explain 
how a proposed NDC can be voluntarily reserved.
    Comments on the NDC provisions of the proposed rule and FDA's 
responses are summarized in this document. This does not include some 
comments that have been made moot by the revisions summarized 
previously.
    (Comment 31) FDA received many comments opposing the proposed 
rule's requirement that FDA, rather than registrants, generate and 
assign the complete NDC for drugs that are subject to listing. Some 
comments were concerned about possible delays associated with NDC 
request submissions. Others were concerned about losing control over 
numbering conventions that individual registrants may apply to their 
own product codes and package codes. One comment expressed concern that 
subjecting OTC monograph products to an NDC assignment process could 
begin to resemble an FDA approval process for such products.
    (Response) The objective behind FDA's proposal to generate and 
assign NDCs was to assure they are assigned appropriately. Although we 
did not intend FDA's issuance of NDCs to be time consuming or to 
operate as an approval process, we recognize that FDA's objectives can 
be met in a way that is more flexible and less burdensome for 
registrants. Accordingly, the proposed requirement that FDA generate 
the complete NDC for each listed drug is not included in this final 
rule.
    Under new Sec.  207.33(d), registrants, not FDA, will generate NDCs 
for assignment to their listed drugs. An NDC is considered to be 
``proposed for assignment'' when a registrant submits it for the first 
time with drug listing information in accordance with Sec.  207.49 or 
Sec.  207.53. If the proposed NDC conforms to the formatting 
requirements of Sec.  207.33, is not reserved for a different drug, and 
was not previously assigned to a different listed drug, FDA will assign 
the proposed NDC when it receives all required listing information for 
the drug.
    (Comment 32) Some comments asked how far in advance of marketing a 
drug for the first time an NDC may be requested. Comments also pointed 
out that manufacturers need to know the NDC for a drug in development 
prior to the time of drug listing.
    (Response) As explained in response to Comment 31, this final rule 
requires registrants to propose their own NDCs for drugs they list. FDA 
will assign a proposed NDC to the drug identified by the registrant if 
the proposed NDC conforms to the formatting requirements of Sec.  
207.33, is not reserved for a different drug, and was not previously 
assigned to a different listed drug.
    We recognize that a mechanism for reserving a specific NDC may be 
helpful, as this would provide greater certainty that a proposed NDC 
will be accepted by FDA when it is included with a listing submission 
at the time of marketing. Accordingly, this final rule includes a new 
Sec.  207.33(d)(3) that allows a person to voluntarily reserve a 
proposed NDC for a period of 2 years prior to its inclusion in a drug 
listing submission for the first time. Note that an NDC reserved under 
Sec.  207.33(d)(3) would need to include most importantly a labeler 
code and a product code. At the discretion of the person submitting the 
reservation request, a single package code could be included, or not, 
with one or more package codes included later in NDC(s) submitted with 
complete drug listing information.
    Certain minimal information must be submitted to reserve a proposed 
NDC, as specified in new Sec.  207.33(d)(3). This information does not 
include identification of the drug's inactive ingredients. Many 
comments opposed the inclusion of such detailed information in the 
proposed rule's provision governing NDC requests.
    NDCs reserved under Sec.  207.33(d)(3) would be reserved for 2 
years unless the person whose labeler code is included in the NDC asks 
FDA to cancel the reservation earlier. If a reserved NDC is not used 
during the 2-year reservation period (i.e., is not submitted to FDA 
with complete listing information for the drug matching the 
reservation), the NDC will be available for assignment to another drug. 
Anyone wishing to extend an NDC reservation beyond 2 years may submit 
another reservation request.
    In addition to the procedure established under Sec.  207.33(d)(3), 
a registrant wishing to reserve an NDC also has the option of 
submitting complete listing information for a drug that is under 
development and specifying a future ``start marketing date'' in the 
listing submission. That listing submission could then be updated, as 
needed, when the actual marketing date arrives.
    (Comment 33) One comment questioned how, when listing a drug for 
the first time, a registrant can supply a drug's labeling if the 
labeling must include the drug's NDC, and if the NDC is not assigned 
until the drug is listed.
    (Response) As explained in response to Comment 1, unlike the 
proposed rule, this final rule does not require NDCs to appear in 
human-readable form on drug labels (but an intervening statutory 
amendment, the DSCSA, does require NDCs to appear as part of the 
product identifier on certain drug labels). After the effective date of 
this final rule, our regulations will continue to encourage, but not 
require, the appearance of human-readable NDCs on drug labels (Sec.  
201.2) and continue to require that NDCs appear in bar codes on drug 
labels (Sec.  201.25(c)).
    Under this final rule, unlike the proposed rule, registrants are 
able to develop and propose their own NDCs to FDA. Upon receipt of a 
first-time listing submission, FDA will assign the NDC proposed by the 
registrant to the drug being listed unless the NDC is improperly 
formatted, reserved for a different drug, or was previously assigned to 
a different listed drug. Registrants are also able to reserve an NDC 
for a drug under development under Sec.  207.33(d)(3) of this final 
rule. Accordingly, registrants should not have difficulty determining, 
with adequate certainty, the NDC for a drug under development.
    (Comment 34) Some comments supported the proposed rule's revocation 
of then-current Sec.  207.35(b)(4)(ii), which stated that the product 
code of a discontinued product could be reassigned to another product 5 
years after the expiration date of the discontinued product or, if 
there is no expiration date, 5 years after the last shipment of the 
discontinued product. Commenters generally agreed that the reuse of old 
NDCs for a different

[[Page 60187]]

product in the future can be confusing. One comment, however, urged FDA 
to allow for the reuse of NDCs.
    (Response) FDA is retaining this general prohibition against the 
reuse of NDCs in the final rule. As indicated in new Sec.  
207.33(d)(2), an NDC will not be assigned to a drug if it was 
previously assigned to a different drug. The prohibition against reuse 
of NDCs applies to listings submitted on or after the effective date of 
this final rule. Drugs that are currently listed under NDCs that have 
been reused in accordance with previous Sec.  207.35(b)(4)(ii) may 
continue to be listed under such NDCs.
    Conversely, if a registrant reintroduces a drug it listed and 
discontinued in the past, that registrant must list the drug using the 
same NDC under which it was listed in the past. See Sec.  207.37(b) of 
this final rule. However, if the reintroduced drug includes changes, 
compared to the discontinued drug, that would warrant a new NDC under 
new Sec.  207.35, then it should be listed under a new NDC.
    As discussed in response to Comment 19, under new Sec.  207.49, if 
a private label distributor uses a contract manufacturer to produce a 
human drug, the contract manufacturer has an obligation to list the 
drug under two NDCs, one that includes the labeler code of the contract 
manufacturer and one that includes the labeler code of the private 
label distributor. If the private label distributor switches to a new 
contract manufacturer in the future, that new contract manufacturer 
would also have an obligation to list the drug under two NDCs, one that 
includes its own labeler code and one that includes the labeler code of 
the private label distributor. The NDC that includes the new contract 
manufacturer's labeler code will obviously differ from the NDC under 
which the previous contract manufacturer listed the drug (because the 
labeler codes will differ). The NDC that includes the private label 
distributor's labeler code may be the same as that under which the 
previous contract manufacturer listed the drug provided: (1) There have 
been no changes to the drug that warrant a new NDC under Sec.  207.35 
and (2) the previous contract manufacturer updates its listing 
information to indicate it no longer manufactures the drug (as it is 
required to do under Sec.  207.57 at the time of its next June or 
December listing update, or sooner at its discretion). If those two 
conditions do not exist, FDA would accept a listing from the new 
contract manufacturer under a new NDC that includes the private label 
distributor's labeler code.
    (Comment 35) We received several comments concerning the format of 
the NDC. Many comments expressed concern about the impact of any 
changes in the NDC format on various systems that track and use NDCs. 
Some comments urged FDA to retain the 10-digit NDC format. Others 
encouraged the adoption of a standard 11-digit NDC. Some comments 
opposed the possible introduction of alphanumeric NDCs, preferring all 
numeric NDCs. Others were concerned about the possible coexistence of 
10- and 11-digit NDCs.
    (Response) FDA is sensitive to these concerns. Section 207.33(b) of 
this final rule specifies the format of an NDC recognized by FDA. The 
final rule necessarily includes more specifications than did the 
proposed rule concerning NDC formatting because under the final rule, 
registrants, not FDA, develop their own proposed NDCs, and they must 
all meet certain formatting parameters. The final rule states, for 
example, that the NDC is 10 or 11 digits to preclude the submission of 
longer NDCs.
    Our regulations have long stated that FDA will expand the labeler 
code from five to six numeric characters when the available five-
character code combinations are exhausted (previous Sec.  
207.35(b)(2)(i)). This occurrence is mathematically inevitable and is 
reflected in new Sec.  207.33(b)(1), which states that the NDC must 
consist of 10 or 11 digits. FDA will begin issuing 6-digit labeler 
codes, leading to 11-digit NDCs, only when the available 5-digit 
labeler codes are exhausted. FDA will not assign 11-digit NDCs until we 
begin to issue 6-digit labeler codes.
    FDA recognizes the desirability of a single, standard format for 
NDCs, having three segments of consistent lengths, as we eventually 
transition to six-digit labeler codes. We intend to initiate a public 
discussion of future formatting options in the near future. In the 
meantime, the provisions included in this final rule are intended to 
accommodate the range of existing NDC formats, leaving room for 
necessary expansion to 11 digits.
    This final rule refers to the NDC as a numeric code, not an 
alphanumeric code. This takes into account comments that objected to 
the inclusion of alpha characters in NDCs as disruptive of current 
systems and practices.
    (Comment 36) Some comments urged FDA not to require NDCs for HCT/
Ps, citing the International Society of Blood Transfusion (ISBT) number 
as a better means of identifying these products.
    (Response) In response to these comments, Sec.  207.33(b)(4) of 
this final rule states that an alternatively formatted NDC may be used 
for certain identified HCT/Ps if they are minimally manipulated and if 
the alternatively formatted NDC is approved by the Center Director 
(CDER or CBER, as appropriate). Such approval may be indicated in 
Guidance for Industry issued by one or both Centers or in this 
preamble, for example. Accordingly, FDA identifies ISBT-128 as a 
currently approved alternatively formatted NDC to identify HCT/Ps 
within the scope of Sec.  207.33(b)(4). ISBT-128 is an international 
standard for the identification of medical products of human origin. 
Please note that an alternatively formatted NDC approved under Sec.  
207.33(b)(4) qualifies as an NDC. HCT/Ps that are not within the scope 
of Sec.  207.33(b)(4) require traditionally formatted NDCs.
    (Comment 37) One comment encouraged FDA to allow a single NDC, with 
a single package code, to be assigned to an API, which may be 
commercially distributed in various quantities.
    (Response) This comment refers to APIs, but the question applies to 
any bulk product supplied in variable quantities. We would like to 
accept non-numeric characters, such as one or more asterisks, in the 
package code segment of an NDC to indicate a bulk product supplied in 
various quantities (as was previously done in paper submissions). 
However, the SPL format, currently specified in the electronic 
registration and listing guidance, does not accommodate non-numeric 
characters. Manufacturers in this situation may adopt a variety of 
practices. They may submit multiple NDCs with package codes 
corresponding to a variety of commonly ordered package sizes. They may 
submit an NDC package code corresponding to 1 kilogram (kg), for 
example, and then treat a shipment of 10 kg as being comprised of 10 
units. In some cases, they may submit an NDC with a package code 
corresponding to a 55-gallon drum, for example, and use that packaging 
to ship 55-gallon orders as well as orders that are slightly less than 
55 gallons in volume.
    (Comment 38) One comment recommended that the NDC for a drug that 
was repacked or relabeled include the product code of the source drug.
    (Response) Section 207.53 of this final rule requires repackers and 
relabelers to list drugs they repack or relabel and requires them to 
submit an appropriate NDC for each such drug that includes the 
repacker's/relabeler's labeler code. It would not be feasible to 
require the NDC for a repacked or relabled drug to include the labeler 
code of the repacker or relabeler combined with the product code of the 
source drug. Such a

[[Page 60188]]

requirement might produce an NDC that was previously assigned to a 
different drug. Because registrants will continue to propose their own 
NDCs under this final rule, a repacker or relabeler may generally adopt 
the convention proposed in the comment, but may not list a drug under 
an NDC that was previously assigned to a different listed drug.
    Listing submissions for repacked or relabeled drugs must also 
include the complete NDC assigned to each finished drug received by the 
registrant for repacking or relabeling (i.e., the source drug), so this 
link will exist in the drug's listing information.
    (Comment 39) Two comments asked whether FDA will assign NDCs to 
products that do not have application numbers, i.e., products that are 
not the subject of an approved application.
    (Response) This question was posed in the context of the proposed 
requirement that registrants request an NDC from FDA by submitting 
information specified in proposed Sec.  207.33(c) prior to a listing 
submission. In the case of finished drugs, proposed Sec.  207.33(c) 
would have allowed registrants to submit an approved U.S. application 
number in place of certain information. As discussed in response to 
Comment 31, this final rule allows registrants to propose their own 
NDCs with listing submissions, and FDA will accept those proposed NDCs 
unless they are formatted incorrectly, reserved for a different drug, 
or previously assigned to a different drug. Under this final rule, NDCs 
are still ``assigned'' only by FDA, after all required listing 
information is received. We affirm that NDCs will be assigned in this 
manner to all drugs subject to the listing requirement, including drugs 
that do not have application numbers. As we have stated in the past 
(e.g., previous Sec.  207.39 and in the preamble to the proposed rule 
(71 FR 51276 at 51305)), FDA's assignment of an NDC does not in any way 
denote FDA approval of a product. Section 207.37 of this final rule 
states that a product may be deemed misbranded if an NDC is used to 
denote or imply FDA approval.
    (Comment 40) Some comments asked how NDCs will be assigned to 
multidrug kits. Here we are addressing kits that do not contain medical 
devices. (See related discussion of drug/device combination products in 
response to Comment 22.)
    (Response) If a product contains more than one finished drug 
product, co-packaged as a kit, and that kit is commercially 
distributed, the kit itself must be listed in accordance with Sec.  
207.41, under Sec.  207.49 or Sec.  207.53, as appropriate. A 
registrant submitting the listing should propose an NDC for the kit 
itself, distinct from any NDCs assigned to individual drug constituents 
contained in the kit. The NDC proposed for the kit should include the 
labeler code of the registrant obligated to submit the listing. If the 
kit is packaged for private label distribution, it should be listed 
under an additional NDC that includes the labeler code of the private 
label distributor.
    (Comment 41) A comment asked whether a finished drug product, 
manufactured under one approved application at two different 
manufacturing sites under the same ownership and control could be 
listed under a single NDC. In this example, the finished product from 
each manufacturing site would have the same composition and physical 
appearance. The comment also asked whether the answer would change if 
the manufacturing sites are located in two different countries.
    (Response) Each manufacturing site would need its own establishment 
registration under Sec.  207.17 unless exempt under section 510(g) of 
the FD&C Act or under Sec.  207.13. (Foreign establishments must 
register only if they manufacture, repack, relabel, or salvage drugs 
that are imported or offered for import into the United States.) With 
respect to the drug listing requirement, the proposed rule and the 
final rule specify in Sec.  207.41(a) that when operations are 
conducted at more than one establishment, and common ownership and 
control exists among all the establishments, the parent, subsidiary, or 
affiliate company may submit listing information for any drug 
manufactured, repacked, relabeled, or salvaged at any such 
establishment. This language allows a registrant that manufactures a 
drug at more than one of its own establishments to submit a single 
listing for that product, while identifying all establishments where 
the registrant manufactures the drug under Sec.  207.49(a)(12). The 
listed drug would have a single NDC in this scenario. The answer does 
not change if one or more manufacturing sites are located outside the 
United States.
    Note, however, that FDA would also accept multiple listings if a 
manufacturer in this situation wished for any reason to submit separate 
listings and NDCs for the same drug manufactured at multiple 
establishments.
    This analysis does not apply to an entity that uses one or more 
contract manufacturers to manufacture, repack, relabel, or salvage a 
drug. In that case, each contract manufacturing site must be registered 
under Sec.  207.17, unless exempt under section 510(g) of the FD&C Act 
or under Sec.  207.13. If more than one contract manufacturing site is 
used, and those sites are under common ownership and control, the 
contract manufacturer could submit a single listing for this drug 
covering its activities at multiple sites (also listing other drugs it 
is required to list under Sec.  207.49 or Sec.  207.53). Furthermore, 
as discussed in our response to comment 19, contract manufacturers must 
generally list a drug under two NDCs, one that includes the contract 
manufacturer's labeler code and one that includes the private label 
distributor's labeler code. In this scenario, a single NDC that 
includes the private label distributor's labeler code could be used 
with a drug manufactured at multiple contractor sites along with a 
single NDC that includes the contract manufacturer's labeler code, 
provided there are no differences in the product produced at the 
various sites that would warrant a new NDC under Sec.  207.35.
    (Comment 42) One comment asked how registrants should assess 
whether their existing NDCs comply with this rule. Some comments noted 
a statement in the preamble to the proposed rule that FDA intends to 
validate that current NDCs comply with the new regulations when the 
rule is finalized (71 FR 51276 at 51280) and requested more information 
about this process.
    (Response) This final rule is not intended to require extensive 
changes to NDCs themselves. The NDC formatting provisions of new Sec.  
207.33(b) are intended to accommodate NDC formats currently in use. The 
10-digit NDC formats provided for under Sec.  207.33(b) of this final 
rule include (in terms of numbers of digits in the labeler code, 
product code, and package code respectively) 4-4-2, 5-3-2, and 5-4-1. 
Any NDC in one of those formats that is not assigned to multiple drug 
products and is not assigned to a non-drug product should comply with 
this final rule. When five-digit labeler codes are exhausted, FDA will 
begin issuing six-digit labeler codes, allowing for additional formats 
of 6-3-2 and 6-4-1.
    (Comment 43) Some comments encouraged FDA to permit one registrant 
or business to maintain more than one labeler code. These comments 
pointed out that mergers and acquisitions in the pharmaceutical 
industry result in corporate entities responsible for drugs listed 
under multiple NDC labeler codes. Consolidation of such NDCs to a 
single labeler code would be burdensome and may not be possible in some 
cases if, for

[[Page 60189]]

example, one product code has been used with two different labeler 
codes.
    (Response) FDA agrees with this comment. We encourage registrants 
and private label distributors to maintain a single labeler code 
wherever possible. But FDA will not require each registrant and private 
label distributor to maintain only one labeler code. This flexible 
approach accommodates mergers and acquisitions. It departs from a 
statement in the preamble to the proposed rule that only one labeler 
code would be used for new NDC numbers that FDA would have assigned 
prospectively for any given manufacturer, repacker, or relabeler (71 FR 
51276 at 51299). It also accommodates situations in which any 
registrant wishes to maintain different labeler codes for different 
product lines or situations in which a registrant risks exhausting all 
available labeler code and product code combinations if the registrant 
operates with a single labeler code. Importantly, new Sec.  
207.33(c)(2) requires each person who is assigned a labeler code to 
update the information required under Sec.  207.33(c)(1). This will 
allow FDA to reliably associate every labeler code with the person to 
whom it is assigned and the person's contact information.
    Registrants and private label distributors who currently have NDC 
labeler codes but for whom FDA does not have up-to-date information 
described in Sec.  207.33(c)(2) on the effective date of this rule are 
required to update their information. FDA may refuse to accept new drug 
listings that include an NDC labeler code for which the information 
required by Sec.  207.33(c)(2) is not current in our system.
    (Comment 44) One comment asked FDA to confirm that a business 
owning many registered establishments may maintain only one labeler 
code, so that all of its NDCs include a single labeler code.
    (Response) FDA prefers that such a business maintain only one 
labeler code, and that it use this single labeler code when proposing 
NDCs for drugs it manufactures, repacks, relabels, or salvages at 
establishments under common ownership and control. However, as 
explained in our response to Comment 43, FDA will not require any 
business to maintain only one labeler code.
    (Comment 45) One comment interpreted the proposed rule as 
preventing an entity that does not distribute its own products from 
maintaining its own labeler code. The comment recommended that such an 
entity not be required to assume distribution responsibilities to 
retain its labeler code.
    (Response) FDA is not certain whether this comment is concerned 
with which NDC would have been required to appear on product labels had 
we finalized the proposed amendments to Sec.  201.2, or more generally 
concerned with the NDCs under which private label distributor products 
are listed. Under Sec.  207.33(c) of this final rule, a labeler code 
must be requested and maintained by any person who engages in 
manufacturing, repacking, relabeling, or private label distribution of 
drug products. The term ``private label distribution'' is defined in 
Sec.  207.1 of this final rule to mean commercial distribution of a 
drug under the label or trade name of a person who did not manufacture, 
repack, relabel, or salvage that drug. A private label distributor does 
not need to physically engage in drug distribution to qualify as a 
private label distributor under this definition and maintain a labeler 
code under Sec.  207.33(c).
    (Comment 46) One comment gave an example of two establishments 
``located in the same geographical location within two cities located 
five miles apart'' and asked whether those establishments would need 
separate NDC labeler codes and registration numbers.
    (Response) Under the final rule's definition of ``establishment,'' 
two establishments located 5 miles apart would not qualify as being at 
``one general physical location'' and would therefore require two 
separate registrations. Each establishment would be associated with its 
own UFI and establishment registration number. As stated in Sec.  
207.17 of this final rule, when operations are conducted at more than 
one establishment and common ownership and control among all the 
establishments exists, the parent, subsidiary, or affiliate company may 
submit registration information for all establishments. Likewise, with 
respect to drug listing information, Sec.  207.41 states that when 
operations are conducted at more than one establishment, and common 
ownership and control exists among all the establishments, the parent, 
subsidiary, or affiliate company may submit listing information for any 
drug manufactured, repacked, relabeled, or salvaged at any such 
establishment. A single labeler code may be used in the NDCs for all 
drugs proposed by such a parent, subsidiary, or affiliate company.
    (Comment 47) A comment asked FDA to confirm that the NDC assignment 
requirement for APIs applies to all APIs, whether they are supplied by 
domestic or foreign establishments.
    (Response) Any drug, including an API, manufactured at a domestic 
establishment for commercial distribution in the United States must be 
listed under Sec.  207.49 unless exempt under Sec.  207.13. As proposed 
and under this final rule, the registration and listing requirements 
apply to foreign establishments whose drugs, including APIs, are 
imported or offered for import into the United States. See Sec. Sec.  
207.13(j), 207.49, and 207.53.
    (Comment 48) Some comments urged FDA to exempt allergenic extract 
products from the NDC requirement or from drug establishment 
registration and listing generally. These comments argued that the 
proposed rule would require manufacturers of allergenic extracts to 
manage a large number of NDCs without obvious benefits.
    (Response) Allergenic extracts are used in the diagnosis and 
treatment of allergies. As such, they are appropriately regulated as 
drugs under the FD&C Act and FDA's regulations. Section 510 of the FD&C 
Act authorizes FDA to exempt certain persons from establishment 
registration (and hence listing) if registration ``is not necessary for 
the protection of the public health.'' We decline to make this finding 
for allergenic extracts. Such an exemption would diminish FDA's ability 
to inspect establishments at which allergenic extracts are manufactured 
and track marketed products.
    Both before and after this final rule, our regulations in part 207 
have required that each listed drug product have an NDC. We understand 
that this requires manufacturers of allergenic extracts to associate a 
unique NDC with each product they manufacture for commercial 
distribution, and this may result in a large number of NDCs. We believe 
the public health benefits associated with drug registration and 
listing outweigh the burden this places on manufacturers to manage a 
large number of NDCs.
    (Comment 49) One comment asked whether drug samples are subject to 
the NDC requirement.
    (Response) Under this final rule, registrants must list drugs they 
manufacture, repack, relabel, or salvage for commercial distribution. 
The term ``commercial distribution'' is defined in a way that 
encompasses free samples. Because any listed drug requires an NDC, 
drugs packaged for distribution as promotional samples are expected to 
have NDCs.
    (Comment 50) Some comments recommended that pharmacy compounded 
drugs be eligible for NDC

[[Page 60190]]

assignment. These comments noted that hospital pharmacies use the NDC 
to reduce medication errors.
    (Response) Drug products compounded by a licensed pharmacist or a 
licensed physician in conformance with section 503A of the FD&C Act are 
generally exempt from drug establishment registration and listing under 
part 207 before and after this final rule, consistent with the 
exemptions for pharmacies and practitioners in section 510(g) of the 
FD&C Act. The DQSA added section 503B to the FD&C Act. Under section 
503B, a compounder can register with FDA as an ``outsourcing 
facility.'' Because the FD&C Act now establishes a separate 
registration and drug product reporting process for such outsourcing 
facilities, this final rule exempts outsourcing facilities from the 
registration and listing requirements of part 207. (See new Sec.  
207.13(k).)
    Compounders that meet the conditions for exemption from 
registration and listing requirements under part 207 may elect to 
voluntarily register and list their products under part 207 and obtain 
NDCs.
2. What changes require a new NDC? (Sec.  207.35)
    Section 207.33(f) of the proposed rule identified the types of 
changes to a drug that require a new NDC. This final rule includes new 
Sec.  207.35 that states with greater clarity the types of changes to a 
drug that require a new NDC. Substantively, new Sec.  207.35 is similar 
to the corresponding requirements in the proposed rule, but the 
provision does not require a new NDC when changes are made to inactive 
ingredients or when the Drug Master File number or Veterinary Master 
File number, if any, assigned to an API changes.
    (Comment 51) Some comments were concerned about the types of 
changes to a drug that would require a new NDC in the proposed rule. In 
particular, many comments opposed the proposed requirement that changes 
in a drug's inactive ingredients would necessitate a new NDC.
    (Response) This proposed requirement--that a change in a drug's 
inactive ingredients would necessitate a new NDC--has not been retained 
in the final rule. Under both the proposed rule and the final rule, any 
change in information submitted with a drug listing must be reflected 
in an updated listing under Sec.  207.57. Certain more significant 
changes also require a new NDC, as specified in new Sec.  207.35. Upon 
careful consideration, we agree with those comments that stated it 
would be unreasonably burdensome to require registrants to submit a new 
NDC each time they change the inactive ingredient composition of a 
product.
    Some comments questioned the scope of the proposed requirement: 
Would it apply to changes from one inactive ingredient supplier to 
another? Would it apply to changes in the quantity at which an inactive 
ingredient is used? Would it apply to changes in the compositional 
specifications of an inactive ingredient?
    The justification for this requirement suggested in the proposed 
rule was that some patients may be sensitive to certain inactive 
ingredients, and a change in NDC would flag for those patients and 
their pharmacists and health care providers that a drug's composition 
may have changed (or that some other characteristic identified in Sec.  
207.35 changed).
    Upon careful consideration, we agree with those comments that 
challenged this justification. Paying attention to changes in NDCs 
would be an inexact way for patients, pharmacists, and health care 
providers to discover changes in inactive ingredients. As proposed and 
under this final rule, updates to drug listing information (including a 
new NDC) will be submitted each June and December, or sooner at the 
registrant's discretion. Thus, manufacturers will not be obligated to 
change an NDC immediately upon changing an inactive ingredient and 
update the NDC on their labels on a batch specific basis.
    Comments pointed out that, particularly in the case of OTC 
monograph products, manufacturers currently have the flexibility to use 
certain inactive ingredients interchangeably. FDA's current guidance 
regarding the labeling of OTC drug products acknowledges this practice 
and includes formatting recommendations to accommodate the practice.\2\ 
The proposed rule did not explain, for example, how the new NDC 
requirement would apply in a situation where the manufacturer of an OTC 
monograph product may have switched inactive ingredients in several 
different batches in the 6 months leading up to a semiannual listing 
update submission.
---------------------------------------------------------------------------

    \2\ See the guidance for industry ``Labeling OTC Human Drug 
Products--Questions and Answers,'' December 2008, pp. 10-11, 
available on the Internet at http://www.fda.gov/Drugs under 
Guidances (Drugs).
---------------------------------------------------------------------------

    Rather than impose this burden on some manufacturers, and 
recognizing that ingredient labeling and reference to batch numbers are 
more useful and exact ways to ascertain a drug's composition, this 
final rule does not require a new NDC when a drug's inactive 
ingredients change.
    (Comment 52) One group of comments expressed concern about the many 
situations in which a new NDC would be needed under the proposed rule. 
In addition to mentioning changes in inactive ingredients, the comments 
cited any addition to a drug's label or labeling, including the 
addition of stickers with delivery and handling instructions and ``any 
material change to a drug's labeling or packaging insert'' as things 
that should not warrant a new NDC. The comments emphasized the burden 
associated with changes to a drug's NDC.
    (Response) Several changes in this final rule will reduce the 
number of occasions when a drug requires a new or additional NDC, 
compared to the proposed rule. See the response to comment 51 regarding 
changes to inactive ingredients. See our response to Comment 17 
regarding the revised definition of ``relabel'' in the final rule to 
exclude the addition or modification of information affixed solely for 
purposes of delivery to a customer, customer identification, or 
inventory management. Under this final rule, changes or additions to a 
label that do not qualify as relabeling do not necessitate a drug 
listing submission and NDC under Sec.  207.53. Section 207.35 of this 
final rule does not include ``any material change'' to a drug's 
labeling or package insert among the changes that necessitate a new 
NDC. Labeling changes are generally not included in new Sec.  207.35. 
Some labeling changes will be incidental to the changes included in new 
Sec.  207.35 (e.g., a change to a drug's established or proprietary 
name), but labeling changes themselves do not trigger the need for a 
new NDC under this final rule. FDA has also determined that changes in 
Drug Master File numbers or Veterinary Master File numbers describing 
APIs, alone, should not necessitate new NDCs. Changes in APIs 
themselves, i.e., a change in the identity of an API, will continue to 
necessitate new NDCs under new Sec.  207.35.
    (Comment 53) The Animal Health Institute noted that Animal Drug 
User Fee Act (ADUFA) fees are assessed for each animal drug NDC. This 
comment pointed out that manufacturers of animal drug products will be 
potentially charged twice for a single drug product due to a change in 
the NDC during a fiscal year or due to multiple listings for a single 
product required under this final rule. The comment urged FDA to exempt 
animal drug manufacturers from paying such extra product fees imposed 
by this final rule.
    (Response) As noted in our response to Comment 52, several changes 
in this

[[Page 60191]]

final rule will reduce the number of occasions when a drug requires a 
new or additional NDC, compared to the proposed rule. Under ADUFA, the 
term ``animal drug product'' means each specific strength or potency of 
a particular active ingredient or ingredients in final dosage form 
marketed by a particular manufacturer or distributor, which is uniquely 
identified by the labeler code and product code portions of the NDC, 
and for which an animal drug application or a supplemental animal drug 
application has been approved. See section 739(3) of the FD&C Act. 
Because product fees are assessed under ADUFA for animal drug products 
meeting this definition, fees are not assessed for unfinished animal 
drugs or animal drugs that are not marketed. However, there may be 
instances where a change is made to a marketed animal drug product that 
necessitates a new NDC for that product during a single fiscal year, 
resulting in a new ADUFA product fee. This is an issue that has existed 
prior to this final rule.
    (Comment 54) One comment asked whether a new NDC will be required 
when a manufacturer changes to a new supplier of an API or, relatedly, 
whether multiple NDCs would be needed if multiple suppliers of an API 
are indicated in an approval application for a finished drug product.
    (Response) Section 207.35 of this final rule requires a new NDC 
when there is a change to any API. This provision includes changes from 
one API to another (e.g., a change from acetaminophen to ibuprofen) and 
changes in the strength of an API. The provision does not encompass 
changes in suppliers and does not require multiple NDC product codes 
corresponding to multiple API suppliers.
    (Comment 55) One comment requested clarification regarding when a 
change in drug product strength will require a new NDC (or when 
multiple strengths will require multiple NDCs). This comment 
distinguished between concentration and strength.
    (Response) Section 207.35 of this final rule requires a new NDC if 
the strength of any API changes. The term ``strength'' is generally 
used to refer to the absolute quantity of API in a single unit dose 
(e.g., 250 milligrams (mg) per tablet). Concentration, on the other 
hand, refers to the amount of an ingredient per defined weight or 
volume of product (e.g., 1 mg/1 milliliter (mL)). Examples of multiple 
strengths requiring separate NDCs include 100 mg/tablet, 250 mg/tablet, 
1 mg/1 mL, and 2 mg/2 mL. Each of these would require its own NDC if 
each is supplied as a unit dose. This is true even though the last two 
concentrations are equivalent.
    (Comment 56) Some comments questioned whether two digits are 
sufficient for the package code segment of the NDC. Relatedly, some 
comments requested clarification regarding the need for a new NDC when 
changes are made to a drug's package size or type. For example, would a 
change from one type of plastic bottle to another necessitate a new 
NDC? Another comment argued that changes in medical gas packaging 
should not necessitate many new NDCs.
    (Response) A 2-digit package code segment accommodates 100 
different packaging configurations, counting ``00'' as one possibility.
    There should be a separate package code for each package size. 
Therefore, if a package is enlarged to hold more of a drug product, it 
would need a new NDC.
    A change in package configuration, such as a change from a bottle 
to a blister pack, would also require a new NDC.
    Under new Sec.  207.35(c), a new NDC (specifically a new package 
code segment) is needed for changes in the composition of packaging 
material that are significant enough so that the packaging type 
description previously submitted is no longer accurate. When submitting 
drug listing information electronically, registrants are currently 
prompted to identify the package type by selecting a choice from a drop 
down list. For example, ``Bottle, Plastic'' is currently one available 
selection in the drop down list. If a registrant originally described 
its packaging material using this term and later switched from one type 
of plastic bottle to another, there would be no need for a new NDC. But 
if a change in packaging material is more significant, from plastic 
bottle to glass bottle, for example, so that a new package type should 
be selected from the drop down list, FDA would require a new NDC with a 
new package code segment to accompany the revised listing under Sec.  
207.35(c). (This discussion pertains only to drug listing obligations. 
Please see the FDA guidance for industry on ``Container Closure Systems 
for Packaging Human Drugs and Biologics'' (May 1999, available on the 
Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) regarding 
filing requirements for changes to container closure systems in the 
case of drug products that are the subject of an approved application 
(NDA, abbreviated new drug application (ANDA), or BLA)).
    Medical gases are generally packaged in tanks, canisters, or 
cylinders. A registrant listing a medical gas would choose the 
appropriate packaging type from the drop down list, populated with such 
terms, in our electronic drug establishment registration and listing 
system. We do not currently require more detail about the composition 
of a tank, canister, or cylinder in which a medical gas is packaged and 
would not require a listing update or a new NDC if the composition of a 
tank, canister, or cylinder changes. Therefore, we do not anticipate an 
unreasonable proliferation of NDCs associated with medical gas 
packaging under this final rule.
    If a registrant exhausts all 100 package codes for a single 
product, that registrant may add a second product code, effectively 
making 100 more package codes available. This provision is reflected in 
Sec.  207.35(c) of this final rule.
    (Comment 57) One comment stated that many minor changes are made to 
a drug's packaging, such as resin composition and size optimization. 
This comment stated that these minor changes are already the subject of 
submissions to FDA, for example, as an annual report (submitted under 
Sec.  314.81(b)(2)), a prior approval supplement to an NDA, or a 
changes-being-effected supplement. This comment implicitly questioned 
the need for new NDC package codes triggered by these changes.
    (Response) Section 207.35(c) of this final rule requires new NDCs, 
specifically new package codes, when changes are made to a drug's 
package size or type. See our response to comment 56 regarding our 
interpretation of this requirement. We acknowledge that certain 
postapproval packaging changes are reported to an NDA, BLA, or ANDA 
consistent with current Sec.  314.70 and FDA http://www.fda.gov/Drugss 
guidance for industry ``Container Closure Systems for Packaging Human 
Drugs and Biologics; Chemistry Manufacturing, and Controls 
Documentation'' (May 1999, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) and to a new animal drug 
application (NADA) or an abbreviated new animal drug application 
(ANADA) consistent with current Sec.  514.8 and FDA's guidance for 
industry ``Chemistry, Manufacturing, and Controls Changes to an 
Approved NADA or ANDA'' (May 2007, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)). These submissions, however, 
do not duplicate or satisfy the Agency's objectives behind drug listing 
and the use of the NDC to identify individual marketed drug products. 
These submissions also are

[[Page 60192]]

not made for drugs that are not subject to the new drug approval 
requirements.
3. What restrictions pertain to the use of the NDC? (Sec.  207.37)
    Proposed Sec.  207.37 set forth restrictions pertaining to the use 
of NDCs. These provisions are retained in the final rule with minor 
revisions. New Sec.  207.37 clarifies that a product improperly bearing 
an NDC may be deemed to be misbranded. Additionally, new Sec.  207.37 
is not addressed only to ``manufacturers, repackers, and relabelers.'' 
Persons who are not subject to part 207 are cautioned against 
concluding that the restrictions stated in Sec.  207.37 do not apply to 
them. Improper use of an NDC, as described in Sec.  207.37, may result 
in a misbranding charge under the FD&C Act, whether or not the 
responsible party is generally subject to part 207.
    (Comment 58) One comment agreed that NDCs should not appear in the 
labeling of dietary supplements, foods, and medical devices, but 
encouraged FDA to exercise enforcement discretion in this area. Other 
comments urged FDA to permit the use of NDCs on medical devices and 
medical foods. Others asked FDA to implement an alternative 
identification system for medical devices before finalizing this rule.
    (Response) Section 207.37 of this final rule states that a product 
may be deemed to be misbranded if an NDC is used on the product but it 
is not subject to part 207. Since publication of the proposed rule, FDA 
has issued a final rule requiring UDIs on medical devices (78 FR 58786, 
September 24, 2013). Section 801.57 of that rule (21 CFR 801.57) 
generally prohibits the use of an NDC on the label of a medical device 
after the date on which it must bear a UDI.
    The use of an NDC on the label of a product that is not regulated 
as a drug may confuse and mislead consumers and health care providers 
into believing FDA regulates the product as a drug. Any enforcement 
actions in this area will be subject to a determination that a product 
violates Sec.  801.57 or is misbranded, or otherwise violates the FD&C 
Act.
    (Comment 59) One comment argued against the proposed rule's 
prohibition against the use of NDCs on non-drug products and asked, if 
this prohibition is retained in the final rule, how long manufacturers 
of such products would have to remove NDCs from their labels.
    (Response) Please see our response to comment 58 regarding the 
nature of Sec.  207.37, specifically our clarification that the use of 
NDCs in the labeling of non-drug products may be handled as misbranding 
violations or as violations of Sec.  801.57 as appropriate. See FDA's 
Unique Device Identifier rule (78 FR 58786) and any guidance FDA may 
issue regarding the compliance deadline for Sec.  801.57. When an NDC 
in the labeling of a non-drug product creates the misleading impression 
that FDA regulates the product as a drug, that product may be subject 
to enforcement action.

E. Listing (Part 207, Subpart D)

1. Who must list drugs and what drugs must they list? (Sec.  207.41)
    Proposed Sec.  207.41 specified who must list drugs, and the 
provision is retained in this final rule. Section 207.41(c) now 
includes more detail about the manner in which drugs manufactured for 
private label distribution are listed.
    (Comment 60) Some comments urged FDA to allow private label 
distributors to list drugs that are distributed under their names.
    (Response) Please see our response to comment 16 regarding the 
definitions of ``private label distributor'' and ``private label 
distribution'' in Sec.  207.1 for a discussion of the responsibilities 
of private label distributors in this final rule. Private label 
distributors are not obligated--by their status as private label 
distributors--to register an establishment or list drugs. They may, 
however, submit drug listing information or establishment registration 
information if acting as the authorized agent of a registrant on whose 
behalf the information is submitted.
2. When, after initial registration of an establishment, must drug 
listing information be submitted? (Sec.  207.45)
    Proposed Sec.  207.45 described an establishment's drug listing 
obligation at the time of initial registration. It stated that an 
establishment must, at the time of initial registration, list any drug 
then being manufactured, repacked, relabeled, or salvaged for 
commercial distribution at the establishment. Section 207.45 is revised 
in this final rule to state that such drugs must be listed no later 
than 3 calendar days after initial registration of the establishment.
    (Comment 61) One comment encouraged FDA to provide flexibility in 
the timing of new drug listing submissions. The comment stated that it 
supported the current requirement of 5 calendar days from the start of 
manufacturing.
    (Response) Several provisions of this final rule relate to the time 
periods within which establishment registrations, drug listings, and 
drug listing updates must be submitted. Section 207.21 states that 
domestic establishments must register for the first time no later than 
5 calendar days after beginning to manufacture, repack, relabel, or 
salvage a drug or an animal feed bearing or containing a new animal 
drug (whether or not commercially distributed). This 5-day window for 
initial establishment registration starts at the beginning of 
manufacture, not the beginning of commercial distribution. Section 
207.45 states that each drug being manufactured, repacked, relabeled, 
or salvaged for commercial distribution at the time of initial 
registration must be listed no later than 3 calendar days after initial 
registration. Thus, the 3-day window established in Sec.  207.45 
relates to those drugs being manufactured at the establishment for 
commercial distribution at the time of initial registration. We will 
interpret the phrase ``for commercial distribution'' in Sec.  207.45 
flexibly as meaning immediate or near-term commercial distribution, not 
for storage prior to an initial product launch.
    FDA recognizes that because it has made findings that nondisclosure 
of most drug listing information would be inconsistent with the 
protection of the public health (see Sec.  207.81), registrants may be 
reluctant to list drugs that have not yet been commercially launched. 
FDA intends to interpret the timing requirements in a way that 
accommodates this concern. FDA also encourages and expects registrants 
to list drugs promptly upon commercial launch (following Sec.  207.45 
or Sec.  207.57 as appropriate), recognizing that manufacturers have an 
incentive to list drugs promptly and have their proposed NDCs assigned 
by FDA. After a drug is listed, it should appear in our public NDC 
database within approximately 1 business day and in our internal 
database almost immediately.
3. What listing information must a registrant submit for a drug it 
manufactures? (Sec.  207.49)
    Proposed Sec.  207.49 identified the information that a registrant 
must provide with a drug listing submission for a drug it manufactures. 
Section 207.49 is retained and reorganized in this final rule. Some 
information included in proposed Sec.  207.33(c) (what information must 
a manufacturer submit before we will assign an NDC number to a drug?) 
has been incorporated into new Sec.  207.49 as drug listing information 
because it is not necessary under this final rule for manufacturers to 
request an NDC from FDA.
    (Comment 62) One comment noted that an approved U.S. application

[[Page 60193]]

number is included with drug listing information identified in Sec.  
207.49 and asked FDA to clarify whether an application must be approved 
before drug listing information is submitted.
    (Response) Section 207.49(a)(7) of this final rule requires 
registrants to provide the approved U.S. application number with 
listing information for a drug if one exists. Thus, Sec.  207.49 
requires that an approved U.S. application number be provided with drug 
listing information only if it exists. Unapproved drugs can and must be 
listed without an application number.
    Drugs that are the subject of an application need not be listed 
until they are manufactured for commercial distribution. Registrants 
who are awaiting approval of an application may voluntarily reserve an 
NDC for the drug that is the subject of the application prior to its 
approval under new Sec.  207.33(d)(3). These registrants are also 
permitted, but not required, to list a drug before it is marketed, 
while providing a future start marketing date.
    (Comment 63) Many comments opposed the submission of production 
volume information with drug listing information.
    (Response) In the preamble to the proposed rule, FDA stated that it 
was considering whether to require establishments to provide the number 
of batches and batch size for each drug subject to the listing 
requirement that they manufactured, repacked, or relabeled since the 
establishment last provided listing information (71 FR 51276 at 51312). 
We have decided not to include such a requirement in this final rule.
    (Comment 64) One comment urged FDA to eliminate the requirement 
that registrants submit representative samples of any other labeling 
for OTC drug products.
    (Response) Section 207.49(a)(14)(ii)(b) of this final rule requires 
that for each human nonprescription drug not subject to section 505 of 
the FD&C Act or section 351 of the PHS Act (i.e., not subject to 
premarket approval), drug listing information include the current 
label, the package insert (if any), and a representative sampling of 
any other labeling. The submission of ``any other labeling'' for such 
drugs is a requirement of section 510(j)(1)(B)(ii) of the FD&C Act.
    (Comment 65) One comment questioned the proposed requirement that 
the ``drug facts'' labeling for OTC drug products be included in drug 
listing information, arguing that required labeling for OTC products is 
set forth in OTC monographs and in FDA's regulations in Sec.  201.66.
    (Response) We disagree with this comment. Section 
207.49(a)(14)(ii)(B) of this final rule requires that labeling 
submitted with drug listing information for human nonprescription drugs 
not subject to section 505 of the FD&C Act or section 351 of the PHS 
Act include the ``content of labeling.'' This term is defined in Sec.  
207.1(b) to include, for these drugs, the drug facts labeling required 
by Sec.  201.66. The submission of drug listing information is the only 
mechanism by which FDA has quick access to the labeling that is 
currently in use for marketed OTC drug products. Furthermore, section 
510(j)(1)(B)(ii) of the FD&C Act requires that the label, package 
insert, and a representative sampling of any other labeling be provided 
with listing information for all such drugs, thus encompassing the drug 
facts labeling.
    (Comment 66) One comment urged FDA to require that drug listing 
information for human OTC drugs include the current product label, but 
not other labeling. This comment also urged FDA to accept such labels 
in portable document format (PDF) files rather than structured product 
labeling (SPL).
    (Response) As explained in response to Comments 64 and 65, the FD&C 
Act requires that drug listing information for OTC human drugs not 
subject to section 505 of the FD&C Act or section 351 of the PHS Act 
include the label, package insert, and a representative sampling of 
``any other labeling.'' Therefore, this comment's recommendation that 
only the current product label (i.e., the container label) be submitted 
for such products is contrary to the FD&C Act, and we decline to adopt 
it. Drug listing information is the only mechanism by which FDA 
collects labeling for such products, and it is important that we have 
it readily available.
    This final rule does not specify a file format for the submission 
of drug listing information, but it does require electronic submission 
in a format FDA can ``process, review, and archive.'' (See Sec.  
207.61(a) of this final rule.) As explained in our electronic 
registration and listing guidance, to facilitate the submission of drug 
establishment registration and drug listing information (including the 
content of labeling), FDA has adopted the use of extensible markup 
language (XML) files in a standard SPL format. The automated submission 
process functions most efficiently and effectively when this 
information is provided in a standardized format with defined code sets 
and codes. Information in a properly created and complete SPL file can 
facilitate processing and allows for greater precision and accuracy 
through the use of coded data fields rather than merely electronic 
text. For these reasons, we will continue to expect drug listing 
information in SPL format.
    In the case of unfinished drugs, Sec.  207.49(a)(15)(iv) requires 
submission of the label (if any) but does not require registrants to 
submit the content of labeling. Because FDA does not currently 
electronically process the labels submitted for unfinished drugs, we 
have accepted and will continue to accept electronic submission 
unfinished drug labels in JPEG (Joint Photographic Experts Group) file 
format.
    (Comment 67) One comment questioned the proposed requirement that 
drug listing information include the name of each inactive ingredient 
in a listed drug. Another comment argued that drug listing submissions 
for animal drug products in particular should not be required to 
identify inactive ingredients.
    (Response) This requirement is retained in the final rule, 
specifically in new Sec.  207.49(a)(5), applicable to both human and 
animal drugs. FDA finds it important to maintain up-to-date inactive 
ingredient information for all marketed drug products. This allows FDA, 
for example, to determine the extent to which a particular inactive 
ingredient is currently in use and identify drug products that contain 
it. FDA does not have access to this information in the form of a 
searchable database outside of our drug registration and listing 
information.
    (Comment 68) We received several comments pertaining to the drug 
listing obligations of contract manufacturers, contract packagers, and 
contract laboratories. One requested clarification regarding the manner 
in which a contract manufacturer or packager would submit listing 
information for an investigational drug manufactured or packaged for 
use in a clinical trial.
    (Response) Contract manufacturers, packagers, and laboratories--
unless they are exempt under section 510(g) of the FD&C Act or Sec.  
207.13--will generally qualify as manufacturers under this final rule 
and will be required to register their establishments. Under Sec.  
207.41 of this final rule, registrants must list drugs they 
manufacture, repack, relabel or salvage for commercial distribution. 
The definition of ``commercial distribution in new Sec.  207.1 excludes 
drugs distributed for investigational use under part 312 (21 CFR part 
312) or part 511 (21 CFR part 511). The drugs referred to in this 
comment may be exempt from listing under this analysis.
    (Comment 69) Another comment asked how a contract manufacturer or

[[Page 60194]]

packager should be expected to submit twice annual drug listing 
updates, attesting for example that there have been no changes to a 
drug's labeling, when the contract manufacturer or packager is not 
responsible for or aware of labeling changes in the ordinary course of 
its business.
    (Response) This comment relates to a wide variety of situations. We 
recognize that contractors play an important role in drug manufacture. 
Some perform specialized operations for another manufacturer (e.g., 
blister packaging), and others perform all manufacturing operations for 
a virtual drug company. Some contract manufacturers handle drugs that 
are the subject of an approved application and are sold under the name 
of the application holder. Others manufacture OTC drugs for multiple 
private label distributors. Each situation will require its own 
analysis under this final rule, and there may be more than one way to 
satisfy the rule's requirements.
    If a contract manufacturer is performing one or more steps in a 
larger manufacturing operation, it may be shipping an unfinished drug 
to another contracting party. In that case, the contract manufacturer 
would submit listing information under Sec.  207.49 for the unfinished 
drug it distributes commercially, i.e., the unfinished drug that leaves 
its registered establishment(s). This would include labeling 
information required under Sec.  207.49(a)(15)(iv), meaning the label 
applied to the unfinished drug. In this scenario, the contract 
manufacturer would not be responsible for listing updates that describe 
labeling changes for the finished drug product, if the contract 
manufacturer does not commercially distribute the finished drug 
product.
    If a contractor is performing all steps or just the final steps in 
a drug manufacturing process, the contractor should describe the 
finished drug product in its listing submission. In some cases, a 
contract manufacturer may be responsible for formulating the product 
and developing its labeling. This might be true in the case of an OTC 
store brand, private label distribution product, for example. In that 
situation, the contracting parties would likely agree that the contract 
manufacturer is in the best position to submit drug listing information 
and updates (as it is required to do under this final rule), and this 
would include the submission of any labeling changes with twice annual 
listing updates. In other cases, a contractor might play a much smaller 
role. It might only place a product manufactured and developed by 
someone else into its final packaging. In that case, the contractor 
would be required by this final rule to submit listing information 
pertaining to the finished drug product, including the twice annual 
updates. The contractor might satisfy this obligation by consulting 
with the drug's developer about any changes in drug listing information 
or by letting the drug's developer act as its authorized agent for the 
submission of drug listing information and updates. At all times, 
however, the actual manufacturer of a drug (or repacker, relabeler, or 
salvager) is legally responsible for ensuring that the requirements of 
this final rule are satisfied.
    (Comment 70) One comment stated that ``the proposed requirement for 
finished product contract testing laboratories to list all of the 
products they test should be eliminated.'' The comment pointed out that 
testing laboratories only handle representative samples of products 
that do not enter the supply chain.
    (Response) This comment addresses an issue that arises under the 
FD&C Act and the drug registration and listing regulations as they have 
long existed. (See the definition of ``manufacturing or processing'' 
that has existed in Sec.  207.3 prior to this final rule.) Testing 
laboratories, whether they test finished drug products or in-process 
materials, may have important roles in drug manufacturing and are 
appropriately treated as manufacturers under part 207 if they engage in 
testing or control procedures necessary for manufacture under current 
good manufacturing practices. Any testing laboratory that qualifies as 
a ``manufacturer'' under this final rule must register its 
establishment(s) where drugs are tested. The listing obligation, 
however, applies only to drugs that a registrant places into commercial 
distribution. Therefore, if a laboratory tests in-process materials or 
finished product and then commercially distributes the tested product, 
e.g., for further processing or for distribution as finished product, 
that laboratory would have an obligation to list the drugs it 
commercially distributes. More likely, however, if the laboratory 
merely tests product samples and reports the test results to another 
party without further distributing the tested samples, it has no 
listing obligation.
    (Comment 71) One comment expressed concern that importers would 
have to identify manufacturers for their drug components and provide a 
chain of custody description for each handler from manufacturer to 
importer.
    (Response) This comment reflects a misunderstanding of a statement 
in the proposed rule describing section 801(d)(3) of the FD&C Act. To 
clarify, Sec.  207.49(a)(12) of this final rule requires a registrant 
listing a drug it manufacturers to provide: (1) The name and UFI of the 
establishment where the registrant manufactures the drug and (2) the 
name and UFI of every other establishment where manufacturing is 
performed for the drug. With respect to this second category of 
information, if the registrant provides a properly assigned and listed 
NDC for unfinished drug(s) it uses to produce the listed drug 
(sometimes referred to as ``immediate source NDCs''), the registrant 
does not need to provide names and UFIs of the upstream establishments.
    (Comment 72) One comment asked FDA to clarify a statement in the 
preamble of the proposed rule regarding certificates of analysis for 
imported articles.
    (Response) This comment reflects a misunderstanding of the proposed 
rule. The passage it refers to quotes section 801(d)(3) of the FD&C Act 
(71 FR 51276 at 51284). Section 801(d)(3) of the FD&C Act applies only 
to certain imported products, and this final rule does not implement 
it.
4. What listing information must a registrant submit for a drug it 
repacks or relabels? (Sec.  207.53)
    Proposed Sec.  207.53 identified the information that a registrant 
must provide with a listing submission for a drug it repacks or 
relabels. Section 207.53 is retained and reorganized in this final 
rule. Some information included in proposed Sec.  207.33(d) (What 
information must a repacker or relabeler submit before we will assign 
an NDC number to a drug?) has been incorporated into new Sec.  207.53 
as drug listing information because it is not necessary under this 
final rule for manufacturers to request an NDC from FDA.
    (Comment 73) A comment from the medical gas industry expressed 
concern about the proposed rule's requirement that repackers identify, 
in drug listing information, the NDC associated with a drug immediately 
before it is received by the repacker for repackaging. This comment 
argued that the complexity of medical gas distribution makes this 
requirement difficult to satisfy.
    (Response) We agree that medical gas repackers would need to 
significantly change the way they currently do business to identify 
immediate source NDCs as specified in the proposed rule. In response to 
this comment, we have included an exception in Sec.  207.53 of

[[Page 60195]]

this final rule so that repackers and relabelers of medical gases are 
not required to include with drug listing submissions the NDC assigned 
to each medical gas they receive for repacking or relabeling.
5. What are the requirements for reviewing and updating listing 
information? (Sec.  207.57)
    Proposed Sec.  207.57 described the requirements for reviewing and 
updating drug listing information. The provision is retained in this 
final rule with editorial revisions intended to improve clarity. 
Additionally, the section now says registrants are encouraged to submit 
listing updates at the time of any change affecting previously 
submitted information. We have also deleted a reference to Sec.  
207.55. Under Sec.  207.55, FDA may ask a registrant to explain the 
basis for its belief that a drug is not subject to approval. We do not 
expect registrants to routinely update information provided to us under 
Sec.  207.55.
    (Comment 74) Some comments opposed the requirement that to satisfy 
the June and December listing update obligation, registrants must 
certify that no changes have occurred if no changes have occurred since 
the last review and update of listing information.
    (Response) The preamble to the proposed rule specifically requested 
comments regarding the burden that may result from the no changes 
certification requirement in the context of drug listing updates (71 FR 
51276 at 51314). We have retained in this final rule the requirement in 
Sec.  207.57(b) that registrants update their submitted drug listing 
information each June and December. The review and updating of drug 
listing information is critical to the integrity of FDA's database. We 
recognize, however, that requiring registrants to submit a twice-annual 
``no changes'' certification, on a product-by-product basis, for each 
of their listings would impose a substantial burden on registrants, 
particularly those that maintain hundreds or thousands of drug 
listings. Therefore, Sec.  207.57 of this final rule requires 
registrants to report changes to drug listing information either at the 
time of any change affecting information previously reported or during 
the next June or December listing update following the change. At the 
time of the annual registration update under Sec.  207.29(b), a 
registrant may submit a blanket ``no changes'' certification covering 
all of its listed drug products for which no changes affecting 
previously reported listing information were made since the last annual 
registration update or listing submission. This blanket, ``no changes'' 
certification applies only to drug listing information that has been 
submitted electronically, as it would be too burdensome for FDA to 
maintain certifications for information that has not been submitted 
electronically. Therefore, it cannot be used to report that drug 
listing information submitted on paper in the past remains current. 
This limitation is intended to ease FDA's administrative burden and 
allow FDA to consider drug listing information to be fully migrated 
from paper submissions to our electronic drug registration and listing 
system.
    Please see our response to Comment 30, which addresses this issue 
in the context of establishment registration updates.
    (Comment 75) One comment stated that the obligation to provide 
updates on individual drug listings within 30 days will demand a great 
deal of resources from manufacturers.
    (Response) This comment did not cite the specific provision of the 
proposed rule at issue. The preamble to the proposed rule acknowledged 
that proposed Sec.  207.57(b) would require that drug listing 
information be reviewed and updated only every June and December, but 
also stated that FDA would request updates to listing information 
within 30 calendar days of a change, to maintain the accuracy of our 
drug listing database (71 FR 51276 at 51314). Under Sec.  207.57 of 
this final rule, registrants are encouraged to submit updated drug 
listing information at the time of any change affecting information 
previously submitted, but they are required to submit such information 
only every June and December.
    (Comment 76) Two comments asked FDA to clarify whether a registrant 
may report all changes to drug listing information when they occur, 
i.e., on a rolling basis, instead of conducting a review and update 
each June and December.
    (Response) Under Sec.  207.57 of this final rule, registrants must 
review and update their drug listing information each June and 
December. This is a requirement of section 510(j)(2) of the FD&C Act. 
Registrants are additionally encouraged, but not required, to update 
drug listing information at the time when changes are made to 
previously reported information. These updates do not, however, take 
the place of the June and December updates, which may be satisfied by a 
no changes certification if no changes have occurred since the last 
review and update. We will read ``since the last review and update'' in 
Sec.  207.57(b)(2) as referring to the registrant's most recent listing 
update for a given drug, whether submitted in June, December, or at any 
other time.
    (Comment 77) One comment encouraged FDA to codify a registrant's 
ability to submit updated listing information at the time a change is 
made, rather than waiting for the next June or December review and 
update. This comment referred to a statement in the preamble to the 
proposed rule stating that registrants are requested to submit listing 
information within 30 days of a change.
    (Response) We agree with this comment and have revised Sec.  207.57 
accordingly. New Sec.  207.57 states that registrants are encouraged to 
submit listing updates at the time of any change affecting information 
previously submitted. This provision of the final rule does not refer 
to a 30-day window for such listing updates. We intend to read ``at the 
time of any change'' flexibly, encouraging registrants to submit 
listing updates as soon as possible, but allowing such updates at any 
time before they are due at the next June or December review and 
update.
    (Comment 78) One comment expressed concern regarding the manner in 
which a drug's discontinuation is to be reported under Sec.  207.57. 
This comment noted that historically, many registrants have waited to 
report that a drug has been discontinued until they no longer have to 
report the drug under applicable agreements with the Centers for 
Medicare and Medicaid Services. According to this comment, if an NDC is 
identified as discontinued while the drug is still in distribution up 
until expiration, there may be problems related to reimbursement and 
other matters.
    (Response) The FD&C Act and Sec.  207.57 of this final rule require 
listing updates, including information that a drug has been 
discontinued, at the latest, at the time of the next June or December 
review and update following the discontinuation. In the case of drugs 
that are subject to part 314, Sec.  314.81(b)(3)(iv) also requires that 
their withdrawal from sale be reported to FDA. The reporting deadline 
under Sec.  314.81(b)(3)(iv) is within 15 working days of the 
withdrawal from sale before the effective date of this final rule and 
within 30 calendar days of the withdrawal from sale after the effective 
date of this final rule. It is important that FDA receive this 
information soon after discontinuation for the integrity of our 
database.
    In this final rule, as in the proposed rule, Sec.  207.57 requires 
registrants, when reporting that a listed drug has been discontinued, 
to provide the expiration

[[Page 60196]]

date of the last lot manufactured, repacked, relabeled, or salvaged. 
FDA regards this date as the ``end marketing date'' and includes it in 
the public NDC database when a drug is reported to be discontinued.
    Please note that, in addition to the requirements just discussed, 
section 506C of the FD&C Act, as amended by FDASIA, requires 
manufacturers of certain drugs that are life-supporting, life-
sustaining, or intended for use in the prevention or treatment of a 
debilitating disease or condition, to notify FDA of a permanent 
discontinuance or certain interruptions in manufacture at least 6 
months prior to the date of discontinuance or interruption or as soon 
as practicable if 6-month's prior notice is not possible.
    (Comment 79) Two comments opposed the requirement in Sec.  207.57 
that registrants provide, for a discontinued drug, the expiration date 
of the last lot manufactured, repacked, relabeled, or salvaged, arguing 
that the expiration date of the last lot provides no assurance that the 
drug product will be available to consumers until that date is reached.
    (Response) As explained in response to Comment 78, our use of the 
expiration date of the last lot as an ``end marketing date'' 
facilitates reimbursement while remaining stock of a discontinued drug 
works its way through distribution.
    (Comment 80) Two comments requested clarification regarding how the 
inclusion of an approved application number in a drug listing 
submission can take the place of the content of labeling in SPL format, 
specifically how updated labeling would be provided at the time of a 
listing update if only the application number is referenced.
    (Response) The proposed rule indicated that if ``a manufacturer 
provides a drug's approved U.S. application number as part of a drug's 
listing information, the labeling required under proposed Sec.  
207.49(g)(1) and . . . 207.49(g)(2) would be deemed to accompany the 
listing information'' (71 FR 51276 at 51309). This was written prior to 
FDA's adoption of SPL as the submission standard and is not an accurate 
reflection of how the process operates today. However, FDA has 
considered how our electronic system can avoid unnecessary duplication 
of effort between the submission of labeling updates to applications 
and the submission of drug listing information.
    Under this final rule, a drug listing submission, whether it 
includes an approved application number or not, must include content of 
labeling as specified in Sec.  207.49. An advantage of the SPL format 
is that it allows the holder of a newly approved application to submit 
the content of labeling once, satisfying its obligations under parts 
314 and 207 in a single submission. Upon initial approval, an applicant 
is required to submit a copy of final approved labeling. An electronic 
drug listing submission that includes the content of labeling in SPL 
format can satisfy this obligation. Even if the drug product is not yet 
ready for commercial distribution upon approval, SPL allows for a 
future start marketing date in the listing information so that a second 
submission is not necessary when the product is commercially launched.
    As discussed in response to Comment 15, most drug labeling changes 
necessitate a listing update under Sec.  207.57 of this final rule. 
Registrants who submit drug listing information through FDA's CDER 
Direct electronic submission portal (as well as those using some 
commercial software) will be able to recall a previous submission, 
including the content of labeling, and make appropriate changes when a 
listing update is due. But reference to an application number alone 
will not satisfy the requirement that updated content of labeling be 
submitted under Sec.  207.57 in this final rule.

F. Electronic Format for Registration and Listing (Part 207, Subpart E)

    Proposed Sec.  207.61 stated that establishment registration and 
listing information must be submitted to FDA electronically. As 
proposed, Sec.  207.61 would have allowed advertisements and some 
labeling to be submitted to FDA either in paper or electronic format. 
In this final rule, Sec.  207.61 is revised for clarity. Additionally, 
the final version of Sec.  207.61 requires electronic submission of all 
establishment registration and listing information, consistent with 
FDAAA (no longer allowing for the submission of advertising on paper), 
unless a waiver is granted, and states that FDA may issue guidance from 
time to time on how to provide information in electronic format. 
Because the SPL format currently used for electronic submission of 
registration and listing information does not accommodate the 
submission of drug advertising, taking into account various types of 
advertising media currently in use, FDA is not currently collecting 
advertisements as part of drug listing information. If this technical 
limitation is resolved, we will explain in future guidance how and what 
registrants should transmit electronically as a representative sampling 
of advertisements. In the meantime, we may ask individual registrants 
to submit a representative sampling of advertisements for specific 
prescription human drug products not subject to section 505 of the FD&C 
Act, relying on our authority under section 510(j)(1)(B)(i) of the FD&C 
Act and Sec.  207.49(a)(14) of this final rule.
    The final version of Sec.  207.61 also clarifies that, while drug 
registration and listing information must generally be submitted in the 
English language, in some cases the content of labeling may be 
submitted in a foreign language along with an accurate English 
translation.
    (Comment 81) One comment stated that information should be included 
in the final rule to address whether FDA intends to develop a separate 
database for animal health products or incorporate animal drugs into 
the proposed electronic drug registration and listing database. The 
comment recommended that if a separate database is planned, information 
on whether the same data elements will be required to obtain an NDC 
number and list products would be helpful.
    (Response) At issue in this rulemaking are changes to FDA's 
regulations governing drug establishment registration and listing, 
i.e., changes to the codified language presented in the proposed rule 
and in this final rule. These regulations do not describe the 
electronic drug registration and listing systems developed by FDA, 
which may change from time to time. Currently, FDA maintains separate 
electronic systems for establishment registration and listing for human 
drugs and for animal drugs. The information that must be submitted with 
a drug listing submission, for both human drugs and animal drugs, is 
described in the regulations codified in part 207 as amended by this 
final rule.
    (Comment 82) One comment noted that at the time of the proposed 
rule and the comment period, FDA's electronic drug registration and 
listing system had yet to be developed. Accordingly, stakeholders were 
unable to comment on an electronic system that had yet to be developed.
    (Response) We understand stakeholder interest in the development of 
our electronic system for drug registration and listing. As noted in 
response to Comment 81, however, the amended regulations adopted in 
this rulemaking do not describe the electronic drug registration and 
listing systems developed by FDA. They generally describe information 
that must be submitted to FDA, and they require that it be submitted 
electronically. Therefore, the proposed rule did not solicit comments 
on the electronic drug

[[Page 60197]]

registration and listing system then under development.
    After the proposed rule was published, Congress amended the FD&C 
Act to require electronic submission of drug establishment registration 
and listing information. To implement this statutory change, FDA 
published draft guidance in 2008 and final guidance in 2009 concerning 
electronic submission of drug establishment registration and listing 
information. Stakeholders had an opportunity to comment on the 
electronic system described in our draft guidance and, as with all FDA 
guidance, have an ongoing opportunity to comment at any time.
    FDA currently accepts drug establishment registration and drug 
listing information submitted electronically. We expect registrants to 
find electronic submission less burdensome than the use of paper forms, 
and we accept comments and suggestions from stakeholders regarding 
improvements to our electronic submission systems.
    (Comment 83) One comment recommended that to facilitate the annual 
review and updating of both establishment registration and drug listing 
information, FDA provide registrants with a report of their current 
registration and listing information.
    (Response) This comment does not relate to language that would be 
included in the codified portion of this final rule, but it does raise 
an important issue we would like to address. At all times, registrants 
are responsible for keeping track of registration and listing 
information they have submitted to FDA and should ensure the 
information is securely stored and can be retrieved.
    Registrants who use an agent to submit establishment registration 
and drug listing information to FDA are encouraged to maintain their 
own records of the submitted information or obtain assurances that the 
agent will do so and will make the information available to the 
registrant on request, including if their business relationship is 
terminated.
    FDA currently maintains publicly searchable databases that can be 
used to confirm an establishment is registered. Information about 
registered blood establishments is available through FDA's electronic 
Blood Establishment Registration (eBER) public query application. 
Information about registered HCT/P establishments is available through 
the Human Cell and Tissue Establishment Registration (HCTERS) public 
query application. Information about registered drug establishments can 
be obtained through FDA's Drug Establishments Current Registration Site 
(DECRS). Additionally, FDA's NDC Directory currently includes listed 
finished drug products, but not unfinished drug products. It may be 
expanded in the future to include all listed drugs. Registrants can 
check these sources and may also request a report of their own 
registration and listing information from CDER's Drug Registration and 
Listing staff.
    (Comment 84) Comments noted that changes to part 11 (21 CFR part 
11) are being considered by the Agency and recommended that electronic 
submission of drug registration and listing information be delayed or 
exempt from compliance with part 11 until these changes have been 
decided.
    (Response) Because of changes to section 510(p) of the FD&C Act 
adopted in FDAAA, registration and listing information is currently 
submitted electronically. Exceptions from the electronic submission 
requirement will be handled in accordance with the waiver provisions in 
this final rule (Sec. Sec.  207.65, 607.22, and 1271.23).
    Part 11 sets forth criteria under which FDA considers electronic 
records and signatures to be trustworthy and reliable. Part 11 applies 
to electronic records that are created, modified, maintained, archived, 
retrieved, or transmitted under statutory and regulatory requirements. 
In 2003, FDA published guidance for industry titled ``Part 11, 
Electronic Records; Electronic Signatures--Scope and Application'' 
(2003 Part 11 Guidance, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) and announced its 
availability in the Federal Register (68 FR 52779, September 5, 2003). 
This guidance announced a reexamination of part 11, a narrow 
interpretation of its scope, and a policy of enforcement discretion 
with respect to certain of its requirements. Part 11 currently remains 
in effect, and FDA's policy of enforcement discretion applies as 
described in the guidance.
    Against this backdrop, the proposed rule included a discussion of 
how FDA intended to apply part 11 to electronic drug registration and 
listing. (See 71 FR 51276 at 51317.) Proposed Sec. Sec.  207.61, 
607.22, and 1271.22 specified that certain requirements of part 11 
would not apply to information submitted to FDA under parts 207, 607, 
and 1271. In Sec.  207.61 of this final rule, the applicability of part 
11 is stated as follows: The submission of advertisements and labeling 
is exempt from the requirements of Sec.  11.10(a), (c) through (h), and 
(k) and the corresponding requirements of Sec.  11.30. Other 
information submitted under part 207, as well as information submitted 
under parts 607 and 1271, is exempt from the requirements of Sec.  
11.10(b), (c), and (e) and the corresponding requirements of Sec.  
11.30. These statements in the codified portion of this final rule are 
intended to be read together with any current FDA guidance concerning 
our enforcement of part 11. For example, FDA's 2003 Part 11 Guidance 
states that we do not intend to take action to enforce compliance with 
the validation and audit trail requirements of part 11. This includes 
requirements described in Sec.  11.10(a) and (e). Until our 2003 Part 
11 Guidance is withdrawn or modified, these statements regarding 
enforcement discretion remain current. Therefore, any person submitting 
information electronically to FDA under this final rule may rely on the 
exemptions from part 11 written into parts 207, 607, and 1271, in 
addition to statements regarding part 11 enforcement discretion in 
current FDA guidance.
    (Comment 85) One comment noted that a citizen petition is currently 
pending before FDA requesting that part 11 be revoked in its entirety 
(Docket No. FDA-2004-P-0036, formerly Docket No. 2004P-0429/CP1). This 
comment asked FDA to respond to the citizen petition before it 
completes this rulemaking.
    (Response) The referenced citizen petition remains under review, 
and the part 11 regulations are currently being implemented as 
explained in FDA's 2003 Part 11 Guidance. FDA's publication of this 
final rule should not be interpreted as providing any indication of the 
manner in which the citizen petition will be resolved.

G. Miscellaneous (Part 207, Subpart F)

    Section 207.81 of the proposed rule identified establishment 
registration and listing information that will be available or not 
available for public disclosure after it is submitted to FDA. Section 
510(f) of the FD&C Act states that establishment registration 
information is available for inspection and drug listing information is 
generally not available for inspection unless the Secretary (by 
delegation FDA) finds that an exemption from disclosure would be 
inconsistent with protection of the public health. Consistent with this 
statutory provision, proposed Sec.  207.81 stated that establishment 
registration information would be generally available for disclosure 
and that most, but not all, drug listing information would be available 
for disclosure, as its nondisclosure would be inconsistent with 
protection of the public health. Generally categorized as not available 
for disclosure in the proposed rule was information obtained under:

[[Page 60198]]

     Proposed Sec.  207.33(d)(1)(ii)--Source NDCs for repacked 
or relabeled drugs submitted in the context of an NDC request for such 
drugs,
     Proposed Sec.  207.54(b)(1)--Source NDCs for salvaged 
drugs, and
     Information submitted as the basis upon which it has been 
determined that a particular drug product is not subject to section 505 
or 512 of the FD&C Act, the premarket approval requirement for new 
drugs and new animal drugs.
    In this final rule, Sec.  207.81 has been revised in several ways. 
The section has been reorganized so that registration and listing 
information that will be available for public disclosure is identified 
in paragraph (a), and exceptions are identified in paragraphs (b) and 
(c). Cited section numbers have been revised, consistent with the 
renumbering of sections in this final rule (and the shifting of some 
information required in the proposed rule as supporting an NDC request 
to information required in the final rule as drug listing information). 
Substantively, Sec.  207.81 of this final rule identifies an expanded 
set of information obtained under the following sections as information 
that will not be available for public disclosure:
     Sec.  207.53(b)--Immediate source NDCs for repacked or 
relabeled drugs;
     Sec.  207.54(a)--Immediate source NDCs for salvaged drugs;
     Sec.  207.54(c)--The name or UFI of an establishment where 
a specific drug is salvaged;
     Sec.  207.55--Information submitted as the basis upon 
which it has been determined that a particular drug is not subject to 
section 505 or 512 of the Federal Food, Drug, and Cosmetic Act or 
section 351 of the Public Health Service Act;
     Sec.  207.33(d)(3)--Information submitted to reserve an 
NDC;
     Sec.  207.49(a)(9)--For unfinished drugs, the number 
assigned to the Drug Master File or Veterinary Master File, if any;
     Sec.  207.49(a)(12)--The names and UFIs of establishments 
where manufacturing is performed for listed drugs and/or immediate 
source NDCs;
     Sec.  207.53(c)--The names and UFIs of establishments 
where repacking or relabeling is performed for listed drugs; and
     Sec.  207.49(a)(5)--The names of any inactive ingredients 
submitted with drug listing information for which the registrant makes 
a valid assertion of confidentiality.
    In this final rule, establishment registration information will be 
available for disclosure, consistent with section 510(f) of the FD&C 
Act, except in limited circumstances as described in Sec.  207.81(c). 
FDA has found that nondisclosure of most drug listing information for 
marketed drugs would be inconsistent with the protection of the public 
health. In most cases, drug listing information is obvious or is 
disclosed elsewhere (e.g., a drug's established and proprietary names, 
its dosage form and route of administration, its active ingredient(s)). 
Specifically, FDA has made a finding that nondisclosure of the listing 
information identified in the following bulleted list would be 
inconsistent with protection of the public health, except in limited 
circumstances as described in Sec.  207.81(c):
     Information obtained under Sec.  207.33 will be available 
for public disclosure, but only after a drug is marketed. This 
information that will be available for public disclosure includes 
information a registrant or private label distributor submits or 
updates under Sec.  207.33(c) to obtain an NDC labeler code but does 
not include information submitted under Sec.  207.33(d)(3) to reserve 
an NDC. Information submitted under Sec.  207.33(c) to obtain a labeler 
code (and updates to the information) includes basic contact 
information for the registrant or private label distributor to whom the 
labeler code is assigned, the types of activities (e.g., manufacture, 
repackaging, or private label distribution) in which the person 
requesting the labeler code engages with respect to drugs, and the 
types of drugs to which the labeler code will be applied. This is not 
necessarily, but is arguably, classified as drug listing information 
because it relates to NDCs and labeler code segments of NDCs. FDA makes 
the finding referred to in section 510(f) of the FD&C Act that 
nondisclosure of this information, in the case of marketed drugs, would 
be inconsistent with protection of the public health. The contact 
information described in Sec.  207.33(c)(1)(i) allows consumers to 
verify in some cases that they do not have a counterfeit product. It 
also provides additional contact information for the consumer's 
reference. Disclosure of the types of activities reported under Sec.  
207.33(c)(1)(ii) may provide additional clarity as to a labeler's role 
in producing or marketing a drug. Information on the types of drugs to 
which a labeler code will be applied, described in Sec.  
207.33(c)(1)(iii), is largely available to the public, but centralizing 
it promotes the free flow of information to interested consumers.
     Most information obtained under Sec.  207.49 (listing 
information a registrant must submit for a drug it manufactures) will 
be available for public disclosure after a drug is marketed. This 
information includes the drug's NDC; its established and proprietary 
name; the name and quantity of each active pharmaceutical ingredient in 
the drug; the name of each inactive ingredient (unless a valid 
assertion of confidentiality is made); the dosage form; the drug's 
approved U.S. application number if any; the drug type (finished vs. 
unfinished, human vs. animal, prescription vs. nonprescription); for 
drugs subject to the imprinting requirements of 21 CFR part 206, the 
drug's size, shape, color, scoring, and code imprint (if any); the 
route or routes of administration of the drug; the schedule of the drug 
under the Controlled Substances Act; advertisements; labeling; contact 
information for private label distributors; OTC monograph references if 
any; and the date on which a drug was introduced into commercial 
distribution. FDA makes the finding referred to in section 510(f) of 
the FD&C Act that nondisclosure of the foregoing information, in the 
case of marketed drugs, would be inconsistent with protection of the 
public health. The drug information described in Sec. Sec.  
207.49(a)(1), (3), (10), (15), and 207.49(b)(1) and (2) will enable 
individuals with concerns about counterfeiting to compare information 
about a product in their possession with information provided to FDA. 
The ingredient information described in Sec. Sec.  207.49(a)(4) and (5) 
will in some cases allow individuals to verify ingredient information 
provided in labeling against FDA's records. The information described 
in Sec. Sec.  207.49(a)(6), (8), and (11) relates to proper physical 
form and use of a drug. The application number described in Sec.  
207.49(a)(7) allows individuals to access disclosable FDA records about 
a drug's approval. Whether and how a drug is scheduled under the 
Controlled Substances Act (Sec.  207.49(a)(13)) relates to safe use of 
the drug. The advertisements and labeling described in Sec. Sec.  
207.49(a)(14) and (15) may include information individuals have not 
seen elsewhere describing the risks and benefits of a drug. 
Furthermore, FDA's disclosure of labeling information obtained under 
Sec.  207.49(a)(15) will allow for the availability of current drug 
labeling information through DailyMed, a computerized repository of 
drug information maintained by the National Library of Medicine. The 
contact information described in Sec.  207.49(a)(16)(ii) may provide 
additional contact information for an

[[Page 60199]]

individual's reference. All of this information is largely available to 
the public, but centralizing it promotes the free flow of information 
to interested consumers, health care providers, and others. Note that 
two types of information obtained under Sec.  207.49 will not be 
available for public disclosure: (1) The names of inactive ingredients 
in a listed drug if the registrant listing the drug makes a valid 
assertion of confidentiality for them at the time of drug listing and 
(2) the number assigned to the Drug Master File or Veterinary Master 
File, if any, that describes the manufacture of an unfinished drug.
     Most information obtained under Sec.  207.53 (listing 
information a registrant must submit for a drug that it repacks or 
relabels) will be available for public disclosure after a drug is 
marketed. This information includes the repacked or relabeled drug's 
NDC, labeling, advertisements, and contact information for private 
label distributors. FDA makes the finding referred to in section 510(f) 
of the FD&C Act that nondisclosure of the foregoing information, in the 
case of marketed drugs, would be inconsistent with protection of the 
public health. The NDC described in Sec.  207.53(a) helps identify who 
repacked or relabeled a drug. Labeling and advertising information 
described in Sec. Sec.  207.53(d) and 207.53(e) may include information 
individuals have not seen elsewhere describing the risks and benefits 
of a drug. Furthermore, FDA's disclosure of labeling information 
obtained under Sec.  207.53(d) will allow for the availability of 
current drug labeling information through DailyMed, a computerized 
repository of drug information maintained by the National Library of 
Medicine. The contact information for private label distributors 
described in Sec.  207.53(f)(2) may provide additional contact 
information for an individual's reference. All of this information is 
largely available to the public, but centralizing it will promote the 
free flow of information. Note that two types of information obtained 
under Sec.  207.53 are not available for disclosure: (1) The NDC 
assigned to a finished drug received by a registrant for repacking or 
relabeling and (2) the name and UFI of establishments where repacking 
or relabeling is performed.
     Some information obtained under Sec.  207.54 (listing 
information a registrant must submit for a drug it salvages) will be 
available for public disclosure after a drug is marketed. This 
information includes the salvaged drug's lot number and expiration 
date. FDA makes the finding referred to in section 510(f) of the FD&C 
Act that nondisclosure of the foregoing information, in the case of 
marketed drugs, would be inconsistent with protection of the public 
health. Disclosure of the lot number and expiration date information 
described in Sec.  207.54(b) may help address any concerns about a 
salvaged product's quality, potency, and shelf life.
     Most information obtained under Sec.  207.57 (information 
registrants must submit when updating listing information) will be 
available for public disclosure. In most cases, information submitted 
under Sec.  207.57 updates information previously submitted under 
Sec. Sec.  207.49, 207.53, or 207.54. The same disclosure rules will 
apply whether information is submitted in an original drug listing 
submission or in an updated listing. Our findings under section 510(f) 
of the FD&C Act, described previously, that nondisclosure of certain 
listing information obtained under Sec. Sec.  207.49, 207.53, and 
207.54 would be inconsistent with protection of the public health apply 
whether the information is obtained in an original listing submission 
or an updated listing submission. Accordingly, the reasons supporting 
this finding discussed previously apply to updates submitted under 
Sec.  207.57. Some information obtained under Sec.  207.57 will not 
have been received previously under Sec. Sec.  207.49, 207.53, or 
207.54. This information includes: (1) The date a registrant 
discontinues the manufacture, repacking, relabeling, or salvaging for 
commercial distribution of a listed drug and the expiration date of the 
last lot manufactured, repacked, relabeled, or salvaged, (2) the date a 
registrant resumes the manufacture, repacking, or relabeling, for 
commercial distribution or a drug previously discontinued, and (3) 
certifications that no changes have occurred since the last listing 
review and update. FDA makes the finding referred to in section 510(f) 
of the FD&C Act that nondisclosure of the foregoing information, in the 
case of marketed or discontinued drugs, would be inconsistent with 
protection of the public health. The date a business discontinues or 
resumes manufacturing a drug, submitted under Sec.  207.57(b)(1)(ii) or 
(iii), may help address concerns some individuals may have about 
whether a drug in their possession is counterfeit. The certification 
that no changes have occurred described in Sec.  207.57(b)(2) will 
inform individuals that drug listing information previously submitted 
to FDA is up to date as of the no changes certification date.
    (Comment 86) One comment requested that FDA not disclose the names 
of inactive ingredients in animal drugs submitted with drug listing 
information. This comment stated that inactive ingredients in animal 
drugs are generally not listed on labels. Another comment urged FDA not 
to place the burden on registrants to proactively request that the 
names of inactive ingredients in human drugs be treated as trade 
secrets.
    (Response) The proposed rule included a discussion about disclosure 
of inactive ingredients reported in drug listing submissions and stated 
that FDA will disclose this information unless it is subject to trade 
secret protection. See 71 FR 51276 at 51321. In this final rule, we are 
codifying that approach by making it clear in Sec.  207.81 that we will 
not disclose the names of any inactive ingredients submitted with drug 
listing information for which the registrant makes a valid assertion of 
confidentiality under Sec.  20.61 or other applicable provision of law.
    This approach will apply to both human and animal drugs in an 
ingredient-specific way. In other words, in the absence of a well-
supported assertion of confidentiality for any given inactive 
ingredient reported under Sec.  207.49, the name of that inactive 
ingredient will be available for public disclosure. The inactive 
ingredient composition of a drug product is of interest to consumers 
and in most cases is already disclosed on drug labels. We find that 
categorical nondisclosure of inactive ingredient information would be 
inconsistent with protection of the public health. It is therefore 
appropriate that FDA consider this information disclosable in the 
absence of a valid assertion of confidentiality that supports 
nondisclosure.
    (Comment 87) One comment urged FDA not to disclose the relationship 
between customs brokers and their clients. This comment noted that the 
proposed rule would have required foreign establishments to identify in 
their establishment registrations each person who imports or offers for 
import their drugs into the United States. The proposed rule would have 
defined the term ``person who imports or offers for import'' broadly to 
include agents and brokers. As with establishment registration 
information generally, this information would have been available for 
disclosure under Sec.  207.81 of the proposed rule.
    (Response) As explained in our response to comment 11, in this 
final rule, we define the term ``person who imports or offers for 
import'' more narrowly than it was defined in the proposed rule. The 
new definition is not intended to include persons operating

[[Page 60200]]

merely as customs brokers. Therefore, a person operating merely as a 
customs broker will not be identified in a foreign establishment's 
registration information and hence will not have its relationship with 
the foreign establishment disclosed under Sec.  207.81.
    (Comment 88) One comment asked FDA to clarify the confidentiality 
of information submitted to obtain an NDC. Several comments stated that 
disclosure of listing information is inappropriate for a yet-to-be 
approved product.
    (Response) As discussed in response to comment 31, under this final 
rule, registrants will propose their own NDCs with drug listing 
submissions. It is not necessary under this final rule to request an 
NDC from FDA and support that request with the information specified in 
Sec.  207.33(c) of the proposed rule. Some of the information specified 
in proposed Sec.  207.33(c) (e.g., the drug's proprietary name and 
established name) has been added to drug listing information required 
under Sec. Sec.  207.49, 207.53, and 207.54 of this final rule. The 
foregoing discussion explains which drug listing information will be 
available for disclosure and that it will not be available for 
disclosure until after the drug is marketed.
    Section 207.33(d)(3) of this final rule allows anyone with a 
labeler code to voluntarily reserve an NDC for a drug product under 
development before it is listed. Information submitted under Sec.  
207.33(d)(3) to reserve an NDC is identified in Sec.  207.81(b)(3) as 
generally exempt from disclosure. Because information submitted to FDA 
under Sec.  207.33(d)(3) will relate to drug products under 
development, this exemption from disclosure prior to marketing is not 
inconsistent with protection of the public health.
    (Comment 89) Two comments stated that under the proposed rule, drug 
listing information would be exempt from public disclosure unless the 
Secretary deemed its release to be necessary. These comments asked FDA 
to clarify the circumstances under which disclosure of drug listing 
information would be considered necessary.
    (Response) These comments reflect a misunderstanding of the 
proposed rule. In the proposed rule, Sec.  207.81 stated unambiguously 
that ``[a]fter a drug is listed, all information obtained for that drug 
under Sec. Sec.  207.33, 207.49, 207.53, and 207.54,'' except for 
stated exceptions, would be made available for public disclosure upon 
request or at FDA's discretion (71 FR 51276 at 51353). We have 
determined, under section 510(f) of the FD&C Act and as explained in 
the foregoing discussion, that most drug listing information relating 
to marketed products will be categorically presumed to be available for 
public disclosure because an exemption from disclosure would be 
inconsistent with protection of the public health. In the foregoing 
discussion, we have explained that Sec.  207.81 of this final rule 
identifies a set of drug listing information that will generally not be 
available for public disclosure.
    (Comment 90) One comment urged FDA not to disclose registration and 
listing information that reveals business relationships among trading 
partners, such as those between a drug's manufacturer and a private 
label distributor or between a manufacturer and a retail service 
repackager.
    (Response) We have carefully considered this comment, along with 
section 510(f) of the FD&C Act and our longstanding rules and policies 
regarding disclosure of registration and listing information. As a 
statutory matter, establishment registration information is generally 
disclosable. (See section 510(f) of the FD&C Act.) Thus, information 
required for establishment registration under Sec.  207.25 of this 
final rule is disclosable.
    This final rule requires that foreign establishments report the 
name of each importer known to the establishment and the name of each 
person who imports or offers to import its drugs into the United 
States. This information is treated as establishment registration 
information under section 510(i) of the FD&C Act and under Sec.  207.25 
of this final rule, rather than as drug listing information. Because 
the information is establishment registration information, both the 
FD&C Act and this final rule require that it be available for public 
disclosure. FDA's intention to make this information available for 
disclosure was highlighted in the proposed rule (71 FR 51276 at 51321).
    Drug listing information will not be available for public 
disclosure under this final rule unless its nondisclosure would be 
inconsistent with protection of the public health, as set forth in 
section 510(f) of the FD&C Act. Most drug listing information is 
obvious or is disclosed elsewhere such as in labeling (e.g., size, 
shape, color, scoring, route of administration, approved application 
number, active ingredient(s)) and its nondisclosure would be 
inconsistent with protection of the public health. However, we 
recognize that, as emphasized in this comment, some drug listing 
information may reveal confidential business relationships. This final 
rule exempts from public disclosure drug listing information obtained 
under Sec.  207.49(a)(12) (name and UFI of the establishments where a 
drug is manufactured and/or immediate source NDCs), Sec.  207.53(c) 
(name and UFI of establishments where repacking or relabeling is 
performed), or Sec.  207.54(c) (name and UFI of establishments where 
salvaging is performed).
    (Comment 91) One comment urged FDA to treat all registration and 
listing information as categorically exempt from disclosure.
    (Response) We decline to take this approach. As explained in the 
foregoing discussion, the disclosure provisions in this final rule are 
consistent with section 510(f) of the FD&C Act, notably its requirement 
that establishment registration information be made publicly available 
and that drug listing information be disclosed only to the extent that 
its nondisclosure would be inconsistent with protection of the public 
health.

H. Human Cells, Tissues, and Cellular and Tissue-Based Products (Part 
1271)

    The proposed rule included relatively minor amendments to part 1271 
to require electronic submission of establishment registration and 
listing information for HCT/Ps. These amendments are retained in this 
final rule with some revisions. Under this final rule, manufacturers of 
HCT/Ps that are regulated solely under section 361 of the PHS Act are 
subject to establishment registration and listing under part 1271. 
Manufacturers of HCT/Ps that are regulated under section 351 of the PHS 
Act or as drugs under section 505 of the FD&C Act are subject to 
establishment registration and listing under part 207. (HCT/Ps that are 
regulated as medical devices under the FD&C Act are subject to 
establishment registration and listing under part 807.)
    (Comment 92) One comment was concerned about the breadth of the 
definition of ``importer'' in proposed Sec.  1271.3(mm). This comment 
noted that the proposed rule's definition of ``importer'' appeared to 
include domestic transplant centers (hospitals) housing patients 
awaiting hematopoietic stem cell (HSC) transplant and argued that 
requiring foreign establishments to identify such hospitals as 
``importers'' would be unreasonably burdensome.
    (Response) Please see our response to Comment 9 regarding the 
definition of ``importer'' in Sec.  207.1. We agree with those comments 
that challenged the proposed definition as too broad, particularly as 
it would have captured downstream recipients of imported products. In 
parts 207, 607, and 1271,

[[Page 60201]]

we have narrowed the new definitions of ``importer'' by adding the 
words ``at the time of entry.'' Therefore, these definitions no longer 
capture downstream recipients such as hospitals.

IV. Compliance Dates

    This final rule is effective November 29, 2016.
    The proposed rule included proposed compliance dates by which 
registrants and other affected persons would be required to comply with 
different aspects of a final rule. For example, we proposed that 
manufacturers, repackers, and relabelers be given 3 years from the 
effective date of a final rule to ensure that the appropriate NDC 
appear on their labels. Proposed compliance deadlines were set forth in 
the preamble to the proposed rule but were not reflected in proposed 
codified regulatory language. (See 71 FR 51276 at 51345.)
    The compliance dates are adjusted in this final rule to account for 
changes we have made in the final rule and to account for our 2009 
implementation of electronic registration and listing under part 207 in 
accordance with revisions to the FD&C Act. Compliance dates associated 
with this final rule are presented in table 2.
    Registrants are encouraged to comply with this final rule as soon 
as possible after its effective date. In many cases, the final rule 
will not necessitate changes in a registrant's current registration and 
listing practices because electronic submission of registration and 
listing information already takes place, and the information currently 
collected generally comports with this final rule. We recognize, 
however, that this final rule introduces new requirements, and some 
registrants will need to adjust their registration and listing 
activities. Table 2 should be read as a statement that FDA intends to 
exercise enforcement discretion between the effective date of this 
final rule and the compliance deadlines set forth in the table with 
respect to changes introduced in this final rule. At all times, 
however, persons subject to registration and listing must fulfill their 
statutory obligations and the relevant regulatory provisions set forth 
in parts 207, 607, and 1271, either before or after the effective date 
of this final rule.

                      Table 2--Compliance Deadlines
------------------------------------------------------------------------
                                           Effective date or compliance
              Requirement                            deadline
------------------------------------------------------------------------
Effective date of the final rule.......  90 days after publication.
Electronic submission of establishment   For products currently subject
 registration and listing information     to part 207, the electronic
 under amended part 207.                  submission requirement in
                                          section 510(p) of the FD&C Act
                                          was largely implemented
                                          through FDA's 2009 electronic
                                          registration and listing
                                          guidance (74 FR 26248). Upon
                                          the effective date of this
                                          final rule, FDA expects
                                          continued electronic
                                          submission of registration and
                                          listing information in
                                          accordance with our electronic
                                          registration and listing
                                          guidance and with new Sec.
                                          207.61. This applies to newly
                                          submitted registration and
                                          listing information as well as
                                          updates to information
                                          previously submitted. FDA will
                                          accept waiver requests in
                                          accordance with Sec.   207.65
                                          of this final rule upon its
                                          effective date.
                                         Two years after the effective
                                          date of this final rule, FDA
                                          intends to remove from our
                                          current electronic database
                                          establishment registration and
                                          listing information submitted
                                          in the past on paper and not
                                          updated with a more recent
                                          electronic submission. The
                                          purpose of this removal is to
                                          purge outdated information
                                          from our database, such as
                                          information registrants failed
                                          to update after discontinuing
                                          a drug product or closing an
                                          establishment. Therefore,
                                          registrants must migrate their
                                          establishment registration and
                                          listing information to our
                                          electronic system (or obtain a
                                          waiver from the electronic
                                          submission requirement) before
                                          that time if they have not
                                          already done so. Registrants
                                          may not rely on a ``no
                                          changes'' certification to
                                          migrate information submitted
                                          in the past on paper to our
                                          electronic system. They must
                                          enter and transmit current
                                          registration and listing
                                          information to FDA
                                          electronically.
Electronic submission of blood           Owners or operators of human
 establishment registration and listing   blood product establishments
 information under amended part 607.      currently register and list
                                          either electronically or by
                                          submitting Form FDA 2830 by
                                          mail. FDA will stop accepting
                                          paper submissions and require
                                          electronic submission of
                                          establishment registration and
                                          product listing information
                                          under amended part 607, unless
                                          individual waivers are
                                          granted, 1 year after the
                                          effective date of this final
                                          rule.
Electronic submission of HCT/P           Owners or operators of HCT/P
 establishment registration and listing   establishments currently
 information under part 1271.             register and list either
                                          electronically or by
                                          submitting Form FDA 3356 by
                                          mail. FDA will stop accepting
                                          paper submissions and require
                                          electronic submission of
                                          establishment registration and
                                          product listing information
                                          under amended part 1271,
                                          unless individual waivers are
                                          granted, 1 year after the
                                          effective date of this final
                                          rule.
Part 207, Subpart B--Registration        Registrants are required to
 (timing of establishment registration    submit and update
 and update submissions and substance     establishment registration
 of the information submitted).           information in accordance with
                                          amended subpart B of part 207
                                          no later than the time when
                                          registration information is
                                          due after the first
                                          anniversary of the effective
                                          date of this final rule. If
                                          the effective date falls
                                          between October 1 and December
                                          31, registrants must submit
                                          information required by
                                          amended subpart B no later
                                          than the next October through
                                          December annual review and
                                          update period.
                                         However, registrants must
                                          comply with new Sec.
                                          207.29(a) (expedited updates
                                          when certain establishment
                                          registration information
                                          changes) upon the effective
                                          date of this final rule.

[[Page 60202]]

 
Part 207, Subpart D--Listing (timing of  Registrants are required to
 drug listing and update submissions      submit and update drug listing
 and substance of the information         information in accordance with
 submitted).                              amended subpart D of part 207
                                          (including the submission of
                                          NDCs that are formatted in
                                          accordance with subpart C of
                                          part 207) no later than the
                                          time when listing information
                                          is due after the first
                                          anniversary of the effective
                                          date of this final rule. If
                                          the effective date falls
                                          during either June or
                                          December, registrants must
                                          submit information required by
                                          subpart D no later than the
                                          June or December listing
                                          update 12 months after the
                                          effective date.
Part 607--Establishment registration     Registrants are required to
 for blood and blood products.            submit and update
                                          establishment registration
                                          information in accordance with
                                          amended part 607 no later than
                                          the time when establishment
                                          registration information is
                                          due after the first
                                          anniversary of the effective
                                          date of this final rule. If
                                          the effective date falls
                                          between October 1 and December
                                          31, registrants must submit
                                          establishment registration
                                          information required by
                                          amended part 607 no later than
                                          the next October through
                                          December annual review and
                                          update period.
                                         However, registrants must
                                          comply with new Sec.   607.26
                                          (amendments to establishment
                                          registration for certain
                                          changes such as ownership or
                                          location) upon the effective
                                          date of this final rule.
Part 607--Listing for blood and blood    Registrants are required to
 products.                                submit and update product
                                          listing information in
                                          accordance with amended part
                                          607 no later than the time
                                          when listing information is
                                          due after the first
                                          anniversary of the effective
                                          date of this final rule. If
                                          the effective date falls
                                          during either June or
                                          December, registrants must
                                          submit information required by
                                          subpart D no later than the
                                          June or December listing
                                          update 12 months after the
                                          effective date.
Part 1271--Establishment registration    Registrants are required to
 for HCT/Ps.                              submit and update
                                          establishment registration
                                          information in accordance with
                                          amended part 1271 no later
                                          than the time when
                                          registration information is
                                          due after the first
                                          anniversary of the effective
                                          date of this final rule. If
                                          the effective date falls in
                                          December, registrants must
                                          submit establishment
                                          registration information
                                          required by amended part 1271
                                          no later than the next
                                          December annual review and
                                          update period under Sec.
                                          1271.21(b).
Part 1271--Product listing for HCT/Ps..  Registrants are required to
                                          submit and update listing
                                          information in accordance with
                                          amended part 1271 no later
                                          than the time when listing
                                          information is due after the
                                          first anniversary of the
                                          effective date of this final
                                          rule. If the effective date
                                          falls during either June or
                                          December, registrants must
                                          submit information required by
                                          amended part 1271 no later
                                          than the June or December
                                          listing update 12 months after
                                          the effective date.
------------------------------------------------------------------------

V. Legal Authority

    We have the legal authority to amend our regulations on foreign and 
domestic establishment registration and listing for human drugs, 
including drugs that are regulated under a BLA, and animal drugs. The 
statutory basis for our authority includes sections 201, 301, 501, 502, 
503, 505, 506, 506A, 506B, 506C, 510, 512, 513-516, 518-520, 701, 704, 
721, 801, and 903 of the FD&C Act (21 U.S.C. 321, 331, 351, 352, 353, 
355, 356, 356a, 356b, 356c, 360, 360b, 360c-360f, 360h-360j, 371, 374, 
379e, 381, and 393); 15 U.S.C. 1451-1561; sections 351 and 361 of the 
PHS Act (42 U.S.C. 262 and 264); and section 122, Pub. L. 105-115, 111 
Stat. 2322 (21 U.S.C. 355 note).
    Section 510(c) of the FD&C Act requires every person upon first 
engaging in the manufacture, preparation, propagation, compounding, or 
processing of a drug to immediately register with the Secretary his 
name, place of business, any such manufacturing establishments and 
their unique facility identifiers, and a point-of-contact email 
address. The provisions in section 510(b) and (d) of the FD&C Act 
require annual registration beginning on October 1 and ending on 
December 31 of each year and registration of additional establishments, 
respectively. Section 510(i) of the FD&C Act requires any establishment 
within any foreign country engaged in the manufacture, preparation, 
propagation, compounding, or processing of a drug that is imported or 
offered for import into the United States to register with the 
Secretary by providing certain information. These provisions, together 
with section 701(a) of the FD&C Act (among others), authorize us to 
require the submission of the registration information specified in the 
final rule. The information specified in this final rule will help us 
identify who is manufacturing, repacking, relabeling, or salvaging 
drugs and where those operations are being performed. In addition, some 
information (e.g., official contact information) will help us 
communicate with establishments more effectively and schedule 
inspections more efficiently.
    Section 510(j)(1) of the FD&C Act requires every person who 
registers to file with the Secretary, at the time of registration, a 
list of all drugs that are being manufactured, prepared, propagated, 
compounded, or processed by the registrant for commercial distribution. 
That list must be prepared in the form and manner prescribed by the 
Secretary and must be accompanied by a copy of labeling (or the label 
and package insert) and, in some cases, advertising. Section 510(j)(2) 
of the FD&C Act requires listing information updates every June and 
December. This listing information gives us a current inventory of 
marketed drugs. These provisions of the FD&C Act and others, together 
with section 701(a) of the FD&C Act, provide authority for requiring 
the

[[Page 60203]]

submission of listing information set forth in this proposal. The drug 
listing information specified in this final rule will help us: (1) 
Develop a more current, robust inventory of drugs as a counter-
terrorism measure; (2) more effectively administer our postmarketing 
surveillance programs; (3) facilitate recalls of products; (4) identify 
drugs or ingredients in short supply in the event of a national 
emergency; and (5) identify drugs marketed in violation of the law.
    Section 510(b) of the FD&C Act requires that information 
registrants supply for annual registration includes a UFI for the 
establishment and includes a point-of-contact email address. FDA 
published final guidance in November 2014 specifying that FDA's 
preferred UFI for drug establishment registration is the DUNS number, 
assigned and managed by Dun & Bradstreet.
    Section 510(p) of the FD&C Act requires electronic submission of 
establishment registration and listing information, unless FDA waives 
the electronic submission requirement in individual cases. 
Establishments that manufacture HCT/Ps currently register and list HCT/
Ps under FDA's regulations in part 1271. Pursuant to authority under 
section 361 of the PHS Act, FDA is requiring electronic submission of 
registration and listing information for HCT/Ps.
    Section 510(j) requires biannual updates of certain listing 
information. Requiring certification under section 701(a) authority 
will help us with the efficient enforcement of the FD&C Act because we 
will be able to distinguish between situations where there has been 
noncompliance with registration and listing requirements from 
situations where there have been no changes in information. The failure 
to register or list under section 510 is a prohibited act under section 
301(p) of the FD&C Act, and the failure to do either renders a drug 
misbranded under section 502(o) of the FD&C Act.

VI. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VII. Economic Analysis of Impacts

A. Introduction

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct us to assess all costs 
and benefits of available regulatory alternatives and, when regulation 
is necessary, to select regulatory approaches that maximize net 
benefits (including potential economic, environmental, public health 
and safety, and other advantages; distributive impacts; and equity). We 
have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the final rule. We believe that this final rule 
is not a significant regulatory action as defined by Executive Order 
12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because the final requirements will not impose a significant 
burden on a substantial number of small entities (annualized costs 
represent at most, 0.01 percent of sales for small firms, and 0.002 
percent for large firms, on average), we certify that the final rule 
will not have a significant economic impact on a substantial number of 
small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``any rule that includes 
any Federal mandate that may result in the expenditure by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more (adjusted annually for inflation) in any one 
year.'' The current threshold after adjustment for inflation is $146 
million, using the most current (2015) Implicit Price Deflator for the 
Gross Domestic Product. This final rule will not result in an 
expenditure in any year that meets or exceeds this amount.

B. Summary of Benefits and Costs

    The full assessment of the economic analysis is available in Docket 
No. FDA-2005-N-0464 (Ref. 1) and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.
    The final rule clarifies and codifies the Congressionally mandated 
requirements in FDAAA and FDASIA, and adds a few additional 
requirements to the information needed to list products. The final rule 
will improve management of the establishment registration and drug 
listing requirements and make these processes more efficient and 
effective for industry and for FDA. Maintaining a comprehensive 
electronic registration and listing system supports implementation of 
the electronic prescribing provisions of the MMA. Because registrants 
submit electronic copies of the drug labeling with their drug listing, 
this rule also ensures the availability of current drug information 
through DailyMed, a computerized repository of drug labeling maintained 
by the National Library of Medicine. Establishment registration 
information helps FDA identify who is manufacturing, repacking, 
relabeling, and salvaging drugs and where those operations are 
performed. Quickly accessible electronic information about each 
establishment in the supply chain will help inform our enforcement 
efforts and improve our oversight of the entire drug supply chain. 
Product listing information also gives FDA a current inventory of drugs 
manufactured, repacked, relabeled, or salvaged for commercial 
distribution. Under current practices, registrants would only update 
listings when the listing information has changed. Consequently, some 
registrants have never submitted listings in an electronic format. By 
requiring electronic listings for all marketed drugs, the final rule 
will modernize our electronic systems and close an existing gap in data 
for drugs that are listed in our legacy system but not currently listed 
in our electronic system. Because the final rule primarily codifies 
current business practices, we anticipate that most of the benefits of 
a modern electronic drug registration and listing system were achieved 
as firms implemented electronic submissions in response to the FDAAA 
and FDASIA legislation. The incremental changes required by the final 
rule will yield benefits in addition to those already achieved. 
However, we lack sufficient information to quantify these marginal 
benefits.
    Table 3 provides an itemized description of each incremental cost 
associated with registration and listing for part 207, part 607, and 
part 1271 registrants. For part 207 registrants, the final rule will 
require immediate source NDCs for unfinished drugs, listing missing 
inactive ingredients, and certification of no changes to their drug 
listings. Without the final rule, FDA faces an information gap because 
companies do not always notify the Agency when they stop marketing a 
product. For part 607 and part 1271 registrants, the requirements are 
quite slight for those that already submit registration and listing 
information electronically and minimal for the much smaller number of 
establishments that need to migrate their paper registration

[[Page 60204]]

and listing records to electronic format. All registrants will incur 
costs associated with reading and understanding the rule and revising 
their standard operating procedures (SOPs), and these items represent 
the largest incremental cost. Most incremental costs are one-time only; 
the only recurring costs are for part 207 registrants for certifying no 
changes to their listings the previous year when they renew their 
registrations.

                                       Table 3--Itemized Incremental Costs
                                                [$ millions] \1\
----------------------------------------------------------------------------------------------------------------
                                                              Number of
         Incremental costs                Frequency        hours per unit     Number of units       Total cost
----------------------------------------------------------------------------------------------------------------
Drugs and biological products
 (part 207):
    Identify source of unfinished   Once.................            0.25  93,700 listings......            $3.1
     drugs (from source NDCs).
    Listing inactive ingredients..  Once.................            0.25  40,800 listings......             1.4
    Listing legacy products.......  Once.................             2.5  26,300 listings......             8.7
    Read and understand the final   Once.................              21  5,900 registrants....            16.5
     rule.
    Revise SOPs for registration    Once.................              19  5,900 registrants....            14.9
     and listing.
    Revise SOPs for reusing NDCs..  Once.................              11  2,950 registrants....             4.3
    Certification of no-change....  Recurring annually...             0.5  7,300 establishments.             0.5
                                   -----------------------------------------------------------------------------
        Total costs (part 207)....  .....................  ..............  .....................            49.4
Human-blood products (part 607):
    Read and understand the final   Once.................              14  2,700 registrants....             5.0
     rule.
    Revise SOPs for registration    Once.................              11  27 registrants.......            0.04
     and listing.
    Migrating records to FDA's      Once.................               1  27 registrants.......             0.0
     electronic systems.
                                   -----------------------------------------------------------------------------
        Total costs (part 607)....  .....................  ..............  .....................             5.1
Human-cell and tissue products
 (part 1271):
    Read and understand the final   Once.................              14  2,800 registrants....             5.2
     rule.
    Revise SOPs for registration    Once.................              11  280 registrants......             0.4
     and listing.
    Migrating records to FDA's      Once.................               1  280 registrants......             0.0
     electronic system.
                                   -----------------------------------------------------------------------------
        Total costs (part 1271)...  .....................  ..............  .....................             5.7
----------------------------------------------------------------------------------------------------------------
\1\ We considered the length of the final rule, the number of small and large firms affected, and the extent
  each firm is affected in order to estimate the burden to read and understand the rule. For part 607
  registration and listing, the cost estimate shown as $0.0 million represents $3,591. For part 1271
  registration and listing, the cost estimate shown as $0.0 million represents $37,240.

    Table 4 summarizes the total incremental costs; total annualized 
costs are $9.0 million when calculated at a 7-percent discount rate 
over 10 years, or $7.5 million when calculated using a 3-percent 
discount rate.

                                                  Table 4--Economic Data: Costs and Benefits Statement
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                    Units
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                               Primary        Low          High                    Discount      Period
                  Category                     estimate     estimate     estimate       Year         rate       covered                Notes
                                             ($millions)  ($millions)  ($millions)    dollars     (percent)     (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized Monetized $ millions/year...  ...........  ...........  ...........  ...........            7
                                                                                                           3
    Annualized Quantified..................  ...........  ...........  ...........  ...........            7
                                                                                                           3
                                            ------------------------------------------------------------------------------------------------------------
    Qualitative............................  The final rule will complete and codify modernization of the registration and listing system, thus allowing
                                             FDA to identify establishments, specific drugs or ingredients, to facilitate recalls or information alerts,
                                             and to exercise competent oversight of this important industry.
                                            ------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $ millions/year...        $ 9.0  ...........  ...........         2014            7           10  Recurring costs include only
                                                   $ 7.5                                   2014            3           10   annual time costs of
                                                                                                                            certifying there are no
                                                                                                                            changes to listings; these
                                                                                                                            costs are unique to part 207
                                                                                                                            registrants.
    Annualized Quantified..................  ...........  ...........  ...........  ...........            7
                                                                                                           3
    Qualitative                              ...........  ...........  ...........  ...........  ...........  ...........  .............................
Transfers:

[[Page 60205]]

 
    Federal Annualized Monetized $ millions/ ...........  ...........  ...........  ...........            7
     year.                                                                                                 3
--------------------------------------------------------------------------------------------------------------------------------------------------------
From/To                                      From:
                                             To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized $ millions/   ...........  ...........  ...........  ...........            7
     year.                                                                                                 3
--------------------------------------------------------------------------------------------------------------------------------------------------------
From/To                                      From:
                                             To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government: No estimated effect..............................................................................................
    Small Business: The final rule will have little impact on small businesses; annualized costs represent, at most, 0.01 percent of annual sales for
     small firms and 0.002 percent for large firms, on average..
--------------------------------------------------------------------------------------------------------------------------------------------------------

C. Response to Comments on the Preliminary Impact Analysis of the 
Proposed Rule

    Most of the comments on the regulatory impact analysis of the 
proposed rule (PRIA) concerned the assignment of NDC numbers and the 
requirement that they be printed on container labels. Because these 
proposed changes are not included in the final rule, the comments are 
moot and are not discussed here. We also do not discuss the comments on 
the analysis of the proposed implementation of mandatory electronic 
registration and listing as this was mandated by FDAAA and largely 
implemented by guidance in 2009. Interested parties were able to 
comment on the burden estimates presented in the draft guidance 
entitled ``Providing Regulatory Submissions in Electronic Format--Drug 
Establishment Registration and Drug Listing'' when it was announced in 
the Federal Register of July 11, 2008 (73 FR 39964) (available on the 
Internet at http://www.fda.gov/Drugs under Guidances (Drugs). The 
remaining comments have been grouped by topic; the order in which they 
are discussed is not a reflection of importance.
    (Comment 93) Some manufacturers believed the PRIA did not address 
the financial impact on their sector of the industry and disagreed with 
the Agency's assertion of no significant economic impact on a 
substantial number of small businesses. In particular, manufacturers of 
medical foods and medical devices did not believe we properly addressed 
the loss of revenue they could experience if they could not use NDC 
numbers on their products. Contract manufacturers felt there should be 
a separate analysis of their sector of the industry as did medical gas 
firms who asserted their numbers were underrepresented.
    (Response) We disagree with the comments. NDC numbers were never 
intended for use on medical foods. The medical food industry began 
using NDCs to simplify reimbursement payments by insurance companies. 
There are other mechanisms that can be used for medical food product 
reimbursement, and the secondary impact from FDA enforcement of 
existing rules is not part of a regulatory impact analysis of new 
requirements. The Unique Device Identification System final rule (78 FR 
58786, September 24, 2013) replaces the use of NDC numbers on medical 
devices with a UDI number. The impact of this change was accounted for 
in that rule.
    The PRIA measured the incremental cost to comply with the new or 
changed requirements on a per-establishment and per-listing basis. Most 
of the data in the analysis of the proposed rule are not relevant for 
the final rule because mandatory electronic submission began in June 
2009 with the statutory implementation authorized by FDAAA; however, 
the methodology is relevant. We estimated the incremental cost for 
registration on a per establishment basis. We included all registered 
establishments in our estimate, so establishments in all industry 
sectors required to register are included in the analysis if they 
comply with the requirement. The information required for each 
establishment is essentially the same. Any economies of scale for a 
large firm to register multiple establishments at one time are 
economically insignificant. The same is true for the incremental cost 
to list products. A contract manufacturer, or a repackager, may have 
more than one product to list, but the information required for each 
product is essentially the same for a contract manufacture and other 
manufacturers. The final rule provides that a private label distributer 
can list the products it distributes on behalf of contract 
manufacturers, but the legal obligation remains the contract 
manufacturers'.
    The Regulatory Flexibility Act requires Agencies to assess the 
regulatory impact on domestic small entities and to analyze options 
that would lessen the burden on small entities. The Small Business 
Administration defines a drug manufacturer as small if it employs fewer 
than 750 people and a biological products entity as small if it employs 
fewer than 500.
    The size of the entity is determined by the total employment of the 
ultimate parent firm, which can include companies outside the drug and 
biological products industries. For example, if a drug manufacturer's 
ultimate parent is a financial holding company that employs more than 
750 people across a variety of industrial and service sectors, the firm 
would be considered large even if employment in drug manufacturing is 
only 100 employees.
    For the proposed rule, we used a crude method, using U.S. Census 
information and a database of FDA's ``Approved Drug Products with 
Therapeutic Equivalence Evaluations'' (commonly referred to as the 
Orange Book) to characterize the number and size of the affected firms 
and used U.S.

[[Page 60206]]

Census data from the 2002 Economic Census and County Business Patterns 
for the financial information in the regulatory flexibility analysis. 
The Census data are reported by North American Industry Classification 
System codes (NAICS). Depending on the survey, the economic data are 
collected on an establishment or firm level. Companies whose primary 
NAICS code is not a drug or biologic manufacturer would not be included 
in the financial survey data. For example, the primary NAICS code for 
many small medical gas companies is not pharmaceutical preparations 
manufacturing (NAICS 325412), so these establishments are not included 
in the Census data for NAICS 325412. Including the financial data for 
medical gas establishments in the analysis would be optimal, but we are 
not aware of publicly available data that would capture this 
information. Although the financial information characterizing the 
industry did not include the medical gas sector, medical gas 
establishments were included in the burden estimates.
    The regulatory impact analysis for this final rule uses Dun & 
Bradstreet information on total employment of the ultimate parent 
company to determine the size of entities affected by the rule, but we 
still use the Census data for NAICS 325412 and 325414 for the financial 
information because of limitations of available data.
    There were a number of comments regarding the burden of submitting 
certain information in listing, in particular batch information, 
inactive ingredients, and certifying that there has been no change to a 
listing.
    (Comment 94) Some comments noted that batch information is already 
included in annual reports for products that require applications, so 
the information is a duplication of effort. These comments also noted 
that this information can change often and adds an additional element 
that needs to be tracked and updated.
    (Response) After considering the comments, FDA has decided not to 
include the batch information requirement in the final rule.
    (Comment 95) Some comments suggested FDA reconsider the requirement 
or frequency of the requirement to certify that no change is necessary 
for listings every June and December. Using the 0.25-hour estimate from 
the proposed rule for the time required to verify and certify a 
listing, one company with 800 products calculated that it would take 
114 hours (around 14, 8-hour days) twice a year to comply with the 
requirement, assuming about 60 percent of their total products did not 
require updates in June and December. Another company with over 7,000 
products said it would take 6 months to validate and certify their 
listings with no changes. They suggested making the no changes 
certification requirement every 2 years rather than biannually. Another 
comment suggested that changing the requirement to certifying by 
establishment, rather than by listing, would result in a savings of $1 
million per year.
    (Response) After considering the comments, we have revised the 
requirement for no changes certification from a per-listing basis to an 
establishment basis. Rather than certifying each June and December that 
there is no change to each individual listing, registrants can certify 
by establishment that the electronically listed products are up to date 
when they annually renew their registrations.
    (Comment 96) Some comments regarding submitting inactive 
ingredients as part of listing stated it was unnecessary, burdensome, 
and in some cases would result in the release of information a company 
considered proprietary. These comments noted that inactive ingredients 
are included in human and animal drug applications and must be listed 
on the labels of OTC products. Some manufacturers of animal drugs 
claimed that inactive ingredients are not customarily supplied on the 
label and were concerned with the release of proprietary information.
    (Response) Although inactive ingredients are identified in product 
applications and, in many cases, on product labels, the information is 
not easily accessible and the names are not fully standardized. Listing 
is the only mechanism by which FDA can readily access ingredient 
information across all products. Entering the inactive ingredients 
using defined terminology increases the accuracy and the efficiency of 
data searches. We use the information in listing to inform many 
processes FDA uses for protecting public health, including surveillance 
for serious drug adverse reactions, inspection of facilities used for 
drug manufacturing and processing, and monitoring drug products 
imported into the United States. To prevent public disclosure of 
information a registrant views as confidential, an inactive ingredient 
can be designated as confidential during the listing process.

VIII. Paperwork Reduction Act of 1995

    This final rule contains information collection requirements that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the 
information collection provisions are shown with an estimate of the 
annual reporting burden. Included in the estimate is the time for 
reviewing instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing each 
collection of information.
    Title: Requirements for Foreign and Domestic Establishment 
Registration and Listing for Human Drugs, Including Drugs That Are 
Regulated Under a Biologics License Application, and Animal Drugs.
    Description: The final rule reorganizes, consolidates, clarifies, 
and modifies current regulations on registering establishments and 
listing drugs codified in part 207 for human and animal drugs, in part 
607 for blood and blood products, and in part 1271 for HCT/Ps. The 
final rule describes when and how to register and list and what 
information must be submitted for registration and listing. The final 
rule clarifies the NDC system for drugs and requires that each drug 
product subject to the listing requirements of this final rule have a 
unique NDC.
    The final rule codifies the current statutory requirement that 
registration and listing information be submitted to FDA electronically 
instead of using paper forms unless a waiver is obtained. Historically, 
drug establishment registration and drug listing information was 
submitted using Form FDA 2656 (Registration of Drug Establishment/
Labeler Code Assignment), Form FDA 2657 (Drug Product Listing), and 
Form FDA 2658 (Registered Establishments' Report of Private Label 
Distributors). Before the enactment of FDAAA, section 510(p) of the 
FD&C Act expressly provided for electronic submission of drug 
establishment registration information upon a finding that electronic 
receipt was feasible, and section 510(j) of the FD&C Act specified that 
drug listing information was to be prepared in the form and manner 
prescribed by FDA. Section 224 of FDAAA, which amended section 510(p) 
of the FD&C Act, now requires electronic drug listing in addition to 
electronic drug establishment registration. In certain cases, and as 
discussed in section VIII.E, if it is unreasonable to expect a person 
to submit registration and listing information electronically, FDA may 
grant a waiver from the electronic submission requirement.
    In June 2009, FDA made available the electronic registration and 
listing

[[Page 60207]]

guidance (74 FR 26248, available on the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) to provide recommendations on fulfilling 
the statutory requirement to submit electronically drug establishment 
registration and drug listing information. The guidance describes the 
types of information to include for purposes of drug establishment 
registration and drug listing and how to prepare and submit the 
information in an electronic format (Structured Product Labeling (SPL) 
files) that FDA can process, review, and archive. In June 2009, FDA 
began accepting submissions required under the part 207 regulations 
into our electronic drug registration and listing system. The format 
for these electronic submissions employs Extensible Markup Language 
(XML) and uses the SPL standard to organize the data within the file. 
This electronic registration and listing enables FDA to employ a number 
of automated validations to ensure the quality of the data received.
    In addition to the information that previously was collected on the 
FDA forms, the electronic registration and listing guidance addresses, 
with respect to part 207, the electronic submission of other 
statutorily required information as follows:
     The name of each importer that is known to the 
establishment (the U.S. company or individual in the United States that 
is an owner, consignee, or recipient of the foreign establishment's 
drug that is imported into the United States) (section 510(i)(1)(A) of 
the FD&C Act);
     The name of each person who imports or offers the foreign 
establishment's drug for import (the name of each agent, broker, or 
other entity, other than a carrier, that the foreign drug establishment 
uses to facilitate the import of its drug into the United States) 
(section 510(i)(1)(A) of the FD&C Act); and
     For a registered foreign drug establishment, the name, 
address, and telephone number of its U.S. agent (Sec.  207.40(c)).
    The electronic registration and listing guidance also recommends 
the voluntary submission of the following additional information, when 
applicable:
     The email address for the United States agent, and the 
telephone number(s) and email address for the importer and person who 
imports or offers for import their drug;
     A site-specific Data Universal Numbering System (DUNS) 
number for each entity (in November 2014, we issued the guidance for 
industry entitled ``Specification of the Unique Facility Identifier 
System for Drug Establishment Registration'' (79 FR 65977, available on 
the Internet at http://www.fda.gov/Drugs under Guidances (Drugs)) and 
obtained OMB approval to broaden the entity identification number 
covered in OMB control number 0910-0045);
     The NDC product code for the source drug that is repacked 
or relabeled;
     Distinctive characteristics of certain listed drugs (i.e., 
the flavor, the color, and image of the actual solid dosage form); and
     Registrants may indicate that they view as confidential an 
inactive ingredient or the registrant's business relationship with an 
establishment.
    We currently have OMB approval under the PRA (OMB control number 
0910-0045) for the information collection in current part 207, the 
information that was submitted using Form FDA 2656, Form FDA 2657, and 
Form FDA 2658, and the information collection set forth in the 
electronic registration and listing guidance, including the electronic 
submission of registration and listing information as required by 
FDAAA. The information collection for current part 607 is approved by 
OMB under OMB control number 0910-0052. The information collection for 
current part 1271 is approved by OMB under OMB control number 0910-
0543.
    In tables 5, 6, 7, and 8, we estimate the total burden to comply 
with the applicable information collection requirements for parts 207, 
607, and 1271 as set forth in this final rule. These burden estimates 
for the applicable regulations will replace some of the currently 
approved estimates in OMB control numbers 0910-0045, 0910-0052, and 
0910-0543. These estimates are based on FDA's experience with reviewing 
registration and listing submissions under part 207 since June 2009 and 
on the number of submissions currently received, the number of 
respondents submitting this information, and the number of registered 
establishments and listed drugs, blood products, and HCT/Ps currently 
in FDA's drug registration and listing database.

A. Registration Information Collection Under Part 207

1. Requirements
    Under Sec.  207.17, manufacturers, repackers, relabelers, and drug 
product salvagers must register their establishments. This is 
consistent with current registration information collection, except 
that PET drug producers are not exempt from registration under the 
final rule, and the final rule states that FDA will accept registration 
information from a private label distributor if it is acting as an 
authorized agent for and submitting information that pertains to an 
establishment that manufactures, repacks, relabels, or salvages drugs.
    Under Sec.  207.21, domestic manufacturers, domestic repackers, 
domestic relabelers, and domestic drug product salvagers must complete 
initial registration of each establishment no later than 5 calendar 
days after beginning to manufacture, repack, relabel, or salvage a 
drug. In addition, foreign manufacturers, foreign repackers, foreign 
relabelers, and foreign drug product salvagers must register each 
establishment before the drug is imported or offered for import into 
the United States. This is consistent with current registration 
information collection.
    The information that must be provided to FDA for registration is 
described in Sec.  207.25. The final rule does not require the 
following currently required information collection:
     Kind of ownership or operation.
     Title of each corporate officer and director.
    The final rule requires the following new registration information 
collection:
     Type of operations performed at each establishment.
     Contact information for the establishment's official 
contact.
    Under Sec.  207.29, registrants must review their registration 
information annually between October 1 and December 31and report all 
changes to their registration information or certify that no changes 
have occurred. In addition to the annual review and update, registrants 
must submit expedited reports of certain changes within 30 calendar 
days of the change. Currently, registrants must renew their 
registration information annually and submit certain amendments to 
registration within 5 days of a change. Section 207.29 differs from the 
current requirement to submit amendments to registration in the 
following ways:
     The final rule lengthens the current time period for 
reporting changes to registration information from 5 days (10 business 
days for a change in United States agent information) to 30 calendar 
days.
     The final rule revokes the current requirement to report a 
change in individual ownership and corporate or partnership structure 
and the current requirement to submit a signed

[[Page 60208]]

statement for a change in a registered establishment's firm name.
    New registration information collected under the final rule 
includes the certification that no changes have occurred and reporting 
certain changes as expedited updates within 30 calendar days.
2. Burden Estimates
    Based on the number of new establishments that currently register 
each year, we estimate that approximately 1,400 registrants will submit 
electronically approximately 2,800 new establishment registrations 
annually. Based on the number of registered establishments in our 
database, we estimate that approximately 10,000 registrants will 
provide approximately 10,000 annual reviews and updates of registration 
information (including expedited updates) or reviews and certifications 
that no changes have occurred.
    The estimates include the registration of establishments for both 
domestic and foreign manufacturers, repackers, relabelers, and drug 
product salvagers, and registration information submitted by anyone 
acting as an authorized agent for an establishment that manufactures, 
repacks, relabels, or salvages drugs. The estimates include an 
additional 80 PET drug producers who are not exempt from registration 
under the final rule and approximately 30 manufacturers of plasma 
derivatives.
    We estimate that it will take approximately 1 hour for registrants 
to submit initial registration information electronically for each new 
establishment.
    We also estimate that it will take approximately 30 minutes for 
each annual review and update of registration information (including 
any expedited updates) or each review and certification that no changes 
have occurred.
    The burden hour estimates are based on our familiarity with the 
amount of time it takes registrants to input registration information 
electronically since June 2009. The estimates are an average of the 
time it would take to register a domestic or foreign establishment and 
an average of the time it would take to review registration information 
and update several registration items in the database or review 
registration information and only certify that no changes have 
occurred.

B. Listing Information Collection Under Part 207

1. Requirements
    Under Sec.  207.41, registrants must list drugs they manufacture, 
repack, relabel, or salvage for commercial distribution. This 
requirement is consistent with current listing information collection, 
except that drug product salvagers are not currently required to list 
under part 207.
    The final rule revises current NDC-related listing submissions as 
follows:
     A registrant must list each drug it manufactures, repacks, 
or relabels using an NDC that includes the registrant's own labeler 
code, regardless of whether the drug is commercially distributed under 
the registrant's own label or trade name or under the label or trade 
name of a private label distributor.
     Each registrant must list each drug it manufactures, 
repacks, or relabels for commercial distribution under the trade name 
or label of a private label distributor using an NDC that includes such 
private label distributor's labeler code.
     During listing, each manufacturer, repacker, or relabeler 
must propose for assignment by FDA an NDC that includes its own labeler 
code for each package size and type of drug that it manufactures, 
repacks, or relabels for commercial distribution.
     If a drug is distributed under the trade name or label of 
a private label distributor, the manufacturer, repacker, or relabeler 
must also propose for assignment by FDA an NDC that includes the 
labeler code of the private label distributor under whose trade name or 
label the drug is distributed, for each package size and type so 
distributed.
     A manufacturer, repacker, relabeler, or private label 
distributor may also reserve a proposed NDC for a drug, before the drug 
is listed, by submitting certain information.
    Under Sec.  207.45, registrants must list, no later than 3 calendar 
days after the initial registration of each establishment, any drug 
being manufactured, repacked, relabeled, or salvaged for commercial 
distribution at that establishment. This requirement is consistent with 
current listing information collection, except that the final rule 
specifies within 3 calendar days after initial registration.
    Under the final rule, the information registrants must submit to 
list a drug, including the information that must be submitted (by a 
registrant or a private label distributor) to receive a labeler code, 
is described in Sec. Sec.  207.33, 207.49, 207.53, 207.54, 207.55, and 
207.61. Under current part 207, we assign a labeler code to each 
registrant and the registrant assigns the product code and the package 
code for each drug product's NDC.
    The listing and NDC information collections required by the final 
rule are already approved by OMB under OMB control number 0910-0045, 
except for the following: (1) The name of each inactive ingredient in a 
listed drug (assertions of confidentiality associated with individual 
inactive ingredients are covered in the electronic registration and 
listing guidance); (2) additional information, such as email address, 
to identify a domestic registrant (identifying information for foreign 
registrants is part of the electronic registration and listing guidance 
information collection and in current Sec.  207.40(c)); (3) the drug 
master file or veterinary master file number, if one exists, must be 
submitted by the manufacturer for an unfinished drug; (4) drug product 
salvagers (who do not repack or relabel) must submit the lot number and 
expiration date and NDC assigned to the drug immediately before the 
drug is received by the drug product salvager; (5) all new labeling for 
a repacked or relabeled drug must be submitted, and not only the 
changed labeling; (6) package type and volume information corresponding 
to the package code segment of the NDC must be submitted; (7) a drug's 
OTC monograph reference (if any) and the date on which the drug was or 
will be introduced into commercial distribution are both requested for 
voluntary submission; and (8) the name and Unique Facility Identifier 
(UFI) of the establishment where the registrant who lists the drug 
manufactures it and the type of operation performed on the drug at that 
establishment, and, if an immediate source NDC is not provided, the 
name and UFI of every other establishment where manufacturing is 
performed for the drug and the type of operation performed at each such 
establishment must be provided.
    Under Sec.  207.57, registrants must update drug listing 
information submitted previously (either when the change is made or, at 
a minimum, each June and December). Registrants must also notify FDA if 
any listed drug has been discontinued from marketing or if any 
discontinued drug has been reintroduced and provide listing information 
for any drug not yet listed (at the time of annual establishment 
registration if not sooner). Under Sec.  207.35, registrants must 
notify us of a change in any of the drug characteristics (except 
certain identifying information) for an NDC in Sec.  207.33, and assign 
a new product code and package code for that drug. Current listing 
information collection does not specifically require any type of 
certification if there are no

[[Page 60209]]

changes, and only material changes to listing information must be 
reported.
2. Burden Estimates
    Based on the number of drugs listed annually since June 2009, we 
estimate that approximately 1,713 registrants will submit 
electronically approximately 12,469 new listings annually (including 
the information submitted to obtain a labeler code and to reserve an 
NDC for future use).
    Based on the number of drugs in our listing database and the 
current number of changes to listing information submitted, we estimate 
that approximately 5,300 registrants will provide approximately 10,000 
June and 10,000 December reviews and updates of listing information--a 
total of approximately 20,000 submissions annually (including the 
information submitted to revise an NDC).
    The estimates for the number of drug listings include both domestic 
and foreign listings, listings submitted by registrants for products 
sold under their own names as well as products intended for private 
label distribution, and information submitted related to an NDC and to 
obtain a labeler code. The estimate for the number of drugs subject to 
the listing requirements includes PET drugs and approximately 30 plasma 
derivatives. The estimates for the number of June and December reviews 
and updates of listing information include the number of changes to 
drug characteristics pertaining to the drug product code to obtain a 
new NDC and the reports of the withdrawal of an approved drug from sale 
under Sec.  314.81(b)(3)(iii).
    Based on our familiarity with the time required to input listing 
information electronically since June 2009, we estimate that it will 
take registrants approximately 1 hour and 30 minutes to submit 
information electronically for each drug they list for the first time 
(for both foreign and domestic registrant listings). These estimates 
are an average of the time it will take manufacturers, repackers, 
relabelers, and drug product salvagers, with drug product salvagers 
taking considerably less time than manufacturers. The estimates include 
the time for submitting the content of labeling and other labeling in 
electronic format. (For drugs subject to an approved marketing 
application, the electronic submission of the content of labeling under 
current Sec.  314.50(l)(1)(i) is also approved under OMB control number 
0910-0001.) We also estimate that it will take approximately 45 minutes 
for each June and December review and update of listing information. 
These estimates are an average of the time it would take to review and 
update listing information or to review and certify that no changes 
have occurred. The estimates include the time for submitting any 
labeling for each drug, changes to the drug's characteristics submitted 
for a new NDC, and reports of the withdrawal of an approved drug from 
sale under Sec.  314.81(b)(3)(iii).

C. Registration and Listing Information Collection Under Part 607

1. Requirements
    Under Sec.  607.22(a) of the final rule, blood establishments must 
submit initial and subsequent registration and product listing 
electronically through the Blood Establishment Registration and Product 
Listing system, or any future superseding electronic system. All 
information submitted under this part must be transmitted to FDA 
electronically. Currently, under Sec.  607.22, manufacturers must 
register establishments and list blood products on Form FDA 2830. The 
requested information is consistent with the current requirement to 
register establishments and list products approved under OMB control 
number 0910-0052. A separate discussion regarding waivers under Sec.  
607.22(b) is discussed in section E.
    Under Sec. Sec.  607.25(a) and 607.25 (b)(3) of the final rule, 
establishments must include the Unique Facility Identifier as part of 
the registration and product listing. The other requested information 
under this regulation is consistent with the current requirements to 
register establishments and list products approved under OMB control 
number 0910-0052.
    Under Sec.  607.25(b)(1) of the final rule, blood establishments 
are required to list blood products by the established and proprietary 
name. This is consistent with the current listing requirement approved 
under OMB control number 0910-0052. Currently, manufacturers of plasma 
derivatives and bulk product substances register and list under both 
parts 607 and 207. The final rule revises this requirement by requiring 
persons who engage solely in the production of plasma derivatives, bulk 
product substances, and recombinant version of plasma derivatives or 
animal derived plasma derivatives to register and list only under part 
207. Any reduction in burden is expected to be minimal (approximately 
20 establishments) and will be reflected under OMB control number 0910-
0052. To be consistent with part 207, we are also deleting the 
reference in part 607 to Form FDA 2250 (National Drug Code Directory 
Input) because this form is no longer being used by CDER or CBER.
    Under current Sec.  607.40, foreign establishments must include 
information for the United States agent as part of its initial and 
updated registration. The final rule requires submission of minimal 
additional information (i.e., email address) for the United States 
agent. This information is consistent with the current registration 
information approved under OMB control number 0910-0052. The final rule 
requires the foreign establishment to report to FDA changes in the 
United States agent's name, address, telephone number, and email 
address within 30 calendar days of the change. The final rule lengthens 
from 10 business days to 30 calendar days the time period for reporting 
changes in the United States agent's information to FDA.
2. Burden Estimates
    Based on the number of new establishments that currently register 
with FDA each year, we estimate 68 establishments will provide new 
establishment registration and product listings annually under 
Sec. Sec.  607.22(a), 607.25(a), and (b)(3).
    We estimate that it takes approximately 60 minutes to provide the 
initial registration and listing information for each new 
establishment.
    Based on the number of establishments that currently submit 
registration and product listing updates, we estimate 2,615 
establishments will provide establishment registration and product 
listing updates annually under Sec. Sec.  607.22(a), 607.25(a), and 
(b)(3).
    We estimate that it takes approximately 30 minutes to provide the 
establishment registration and listing update information for 
establishment.
    These burden hour estimates are based on institutional experience 
with the current registration and listing requirements.

D. Registration and Listing Information Collection Under Part 1271

1. Requirements
    Under Sec.  1271.22, establishments must register, list products, 
and provide updates electronically. The current regulation includes the 
option to submit registration, listing, and updates electronically.
    Under Sec.  1271.25, establishments must also submit the telephone 
number and email address of the reporting official. Each foreign 
establishment must submit the name, the address, telephone number, and 
email address of each importer that is known to the

[[Page 60210]]

establishment and the name of each person who imports or offers for 
import such HCT/P to the United States. Foreign establishments must 
also submit the name, the address, telephone number, and email address 
of their United States agent.
    Under Sec.  1271.26, establishments must report a change to the 
United States agent's name, address, telephone number, or email 
address. The final rule will also lengthen to 30 calendar days the 
current requirement of reporting the changes within 5 days.
2. Burden Estimates
    Based on the number of new establishments that currently register 
with FDA each year, we estimate that approximately 225 establishments 
will provide new establishment registration annually. Based on 
information from FDA's database, we estimate that approximately 2,700 
establishments are registered and listed with FDA and will provide 
establishment and listing updates. The number of establishments that 
currently register and list with FDA includes both foreign and domestic 
establishments. If no change has occurred, an update is not required. 
Based on the number of establishments from FDA's database, we estimate 
that approximately 1,200 establishments will provide changes to 
establishment ownership or location, or changes to the United States 
agent's information.
    We estimate that it would take approximately 45 minutes to provide 
the initial registration and listing information for each new 
establishment.
    We estimate that it would take approximately 30 minutes for each 
annual review and update of registration and listing information for 
each establishment.
    We estimate that it would take approximately 15 minutes for each 
establishment to provide a change in ownership and location, or a 
change to the U.S. agent's information.
    These burden hour estimates are based on institutional experience 
with the current registration and listing requirements. The estimates 
are an average of the time it would take to register an establishment, 
and an average of the time it would take to review registration and 
listing information, and update several registration and listing items 
in the database.

E. Waiver Request Information

1. Part 207
    Under Sec.  207.65, registrants may request a waiver from the 
requirement in Sec.  207.61 that information must be provided to us in 
electronic format. We expect very few waiver requests because only a 
computer, Internet access, and an email address are needed to register 
and list electronically and because electronic submission has been 
required since June 2009.
    We estimate that approximately one registrant will request a waiver 
annually and that each request will take approximately 30 minutes to 
prepare and submit to us.
2. Part 607
    Under Sec.  607.22(b), both domestic and foreign establishments may 
request a waiver from the requirement that information must be provided 
to FDA in electronic format. We expect few waiver requests because only 
a computer, Internet access, and an email address are needed to 
register and list electronically.
    We estimate that approximately 25 manufacturers will request a 
waiver annually and that each request will take approximately 1 hour to 
prepare and submit to us.
    When we grant a request for a waiver, we intend to make available 
to the manufacturer the paper form--Form FDA 2830 for registration and 
listing.
3. Part 1271
    Under Sec.  1271.23, manufacturers may request a waiver from the 
requirement in Sec.  1271.22 that information must be provided to FDA 
in electronic format. We expect a limited number of waiver requests 
because only a computer, Internet access, and an email address are 
needed to register and list electronically.
    We estimate that approximately 100 manufacturers will request a 
waiver annually and that each request will take approximately 1 hour to 
prepare and submit to FDA.
    When we grant a request for a waiver, we intend to make available 
to the manufacturer the paper form--revised Form FDA 3356 for 
registration and listing.

F. Public Disclosure Exemption Requests

    Under Sec.  207.81(c), registrants may request that certain 
information in Sec.  207.81(a) not be made available from their 
registration and listing information. Based on our experience with 
registration and listing information inspection requests under current 
Sec.  207.37, we estimate that approximately 100 registrants will 
submit this request annually and that each request will take 
approximately 1 hour to prepare and submit to us. (Assertions of 
confidentiality associated with individual inactive ingredients or the 
registrant's business relationship with an establishment is part of the 
June 2009 electronic registration and listing guidance information 
collection and is covered under OMB control number 0910-0045).

G. Standard Operating Procedure for Electronic Submission

    The requirement under section 510(p) of the FD&C Act for electronic 
drug establishment registration and electronic drug listing resulted in 
our amending OMB control number 0910-0045 in June 2009 to include the 
burden for preparing a standard operating procedure (SOP) for the 
electronic submission requirement, creating the SPL file, including 
accessing and reviewing the technical specifications and instructional 
documents provided by FDA, reviewing and selecting appropriate terms 
and codes used to create the SPL file, obtaining the digital 
certificate used with FDA's electronic submission gateway, and 
uploading the SPL file for submission. Although most registrants have 
already prepared an SOP for the electronic submission requirements, 
each year additional firms will need to create an SOP. As provided in 
table 6, FDA estimates that approximately 1,000 firms will have to 
expend a one-time burden to prepare, review, and approve an SOP, and we 
estimate that it will take approximately 40 hours per recordkeeper to 
create 1,000 new SOPs, for a total of 40,000 hours. We also estimate 
approximately 3,295 hours for annual recordkeeping maintenance of these 
records.

H. Capital Costs

    There are one-time capital costs associated with this rulemaking. 
These costs are discussed in section VII, ``Economic Analysis of 
Impacts.''
    Description of Respondents: Manufacturers, repackers, relabelers, 
drug product salvagers, and private label distributors as described in 
the final rule.
    Burden Estimate: Tables 5, 6, 7, and 8 provide the annual reporting 
and recordkeeping burdens for this final rule.

[[Page 60211]]



                            Table 5--Estimated Annual Reporting Burden Under Part 207
----------------------------------------------------------------------------------------------------------------
                                                     Number of                       Hours per
  21 CFR Sections and reporting      Number of     responses per   Total annual    registration     Total hours
          requirements              respondents     respondent       responses      or listing
----------------------------------------------------------------------------------------------------------------
Initial Establishment                      1,400               2           2,800               1           2,800
 Registration (Sec.  Sec.
 207.17, 207.21, 207.25)........
Annual Review and Update of               10,000               1          10,000            0.50           5,000
 Registration Information
 (including expedited updates)
 (Sec.   207.29)................
Initial Listing (including NDC)            1,713            7.28          12,470             1.5          18,705
 Information (Sec.  Sec.
 207.33, 207.41, 207.45, 207.49,
 207.53, 207.54, 207.55)........
June and December Review and               5,300              20         106,000            0.75          79,500
 Update (or Certification) of
 Listing (including NDC)
 Information (Sec.  Sec.
 207.35, 207.57)................
Waiver requests (Sec.   207.65).               1               1               1            0.50             0.5
Public disclosure exemption                  100               1             100               1             100
 requests (Sec.   207.81(c))....
                                 -------------------------------------------------------------------------------
    Total Reporting Burden......  ..............  ..............  ..............  ..............         106,105
----------------------------------------------------------------------------------------------------------------


                          Table 6--Estimated Annual Recordkeeping Burden Under Part 207
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
 SOP for creating and uploading      Number of      records per    Total annual         per         Total hours
          the SPL File             recordkeepers   Recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
One-time preparation of SOP.....           1,000               1           1,000              40          40,000
SOP maintenance.................           3,295               1           3,295               1           3,295
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          43,295
----------------------------------------------------------------------------------------------------------------


                            Table 7--Estimated Annual Reporting Burden Under Part 607
----------------------------------------------------------------------------------------------------------------
                                                     Number of
         21 CFR Sections             Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
Initial Establishment                         68               1              68               1              68
 Registration and Product
 Listing (607.22(a) and
 607.25(a) and (b)(3))..........
Annual Review and Update of                2,615               1           2,615             0.5           1,308
 Establishment Registration and
 Blood Product Listing
 (607.22(a) and 607.25(a) and
 (b)(3))........................
Waiver requests (607.22(b)).....              25               1              25               1              25
                                 -------------------------------------------------------------------------------
    Total Reporting Burden......  ..............  ..............  ..............  ..............           1,401
----------------------------------------------------------------------------------------------------------------


                           Table 8--Estimated Annual Reporting Burden Under Part 1271
----------------------------------------------------------------------------------------------------------------
                                                     Number of
         21 CFR Sections             Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
Initial Establishment                        225               1             225            0.75          168.75
 Registration and Listing
 (1271.25)......................
Annual Review and Update of                2,700               1           2,700             0.5           1,350
 Establishment Registration and
 Listing (1271.25)..............
Waiver requests (1271.23).......             100               1             100               1             100
Amend Establishment Registration           1,200               1           1,200            0.25             300
 (1271.26)......................
                                 -------------------------------------------------------------------------------
    Total Reporting Burden......  ..............  ..............  ..............  ..............        1,918.75
----------------------------------------------------------------------------------------------------------------

    The information collection provisions of this final rule have been 
submitted to OMB for review, as required by section 3507(d) of the PRA. 
Prior to the effective date of this final rule, FDA will publish a 
notice in the Federal Register announcing OMB's decision to approve, 
modify, or disapprove the information collection provisions in this 
final rule. An Agency may not conduct or sponsor, and a person is not 
required to respond to, a collection of information unless it displays 
a currently valid OMB control number.

IX. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the Agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

[[Page 60212]]

X. References

    The following reference is on display in the Division of Dockets 
Management, (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852, and is available for viewing by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday. It 
is also available electronically at http://www.regulations.gov and at 
http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

1. FDA/Economics Staff, ``Requirements for Foreign and Domestic 
Establishment Registration and Listing for Human Drugs, Including 
Drugs That Are Regulated Under a Biologics License Application, and 
Animal Drugs, Final Regulatory Impact Analysis, Final Regulatory 
Flexibility Analysis, Unfunded Mandates Reform Act Analysis,'' 2016.

List of Subjects

21 CFR Part 20

    Confidential business information, Courts, Freedom of information, 
Government employees.

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 207

    Drugs, Reporting and recordkeeping requirements.

21 CFR Part 314

    Administrative practice and procedure, Confidential business 
information, Drugs, Reporting and recordkeeping requirements.

21 CFR Parts 514 and 515

    Administrative practice and procedure, Animal drugs, Confidential 
business information, Reporting and recordkeeping requirements.

21 CFR Part 601

    Administrative practice and procedure, Biologics, Confidential 
business information.

21 CFR Part 607

    Blood.

21 CFR Part 1271

    Biologics, Drugs, Human cells and tissue-based products, Medical 
devices, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, 21 CFR parts 20, 201, 207, 314, 514, 
515, 601, 607, and 1271 are amended as follows:

PART 20--PUBLIC INFORMATION

0
1. The authority citation for part 20 continues to read as follows:

    Authority: 5 U.S.C. 552; 18 U.S.C. 1905; 19 U.S.C. 2531-2582; 21 
U.S.C. 321-393, 1401-1403; 42 U.S.C. 241, 242, 242a, 242l, 242n, 
243, 262, 263, 263b-263n, 264, 265, 300u-300u-5, 300aa-l.


Sec.  20.100  [Amended]

0
2. Amend Sec.  20.100(c)(9) by removing ``Sec.  207.37'' and by adding 
in its place ``Sec.  207.81''.

0
3. Revise Sec.  20.116 to read as follows:


Sec.  20.116  Drug and device registration and listing information.

    Information submitted to the Food and Drug Administration pursuant 
to section 510(a) through (j) of the Federal Food, Drug, and Cosmetic 
Act shall be subject only to the special disclosure provisions 
established in Sec. Sec.  207.81 and 807.37 of this chapter.

PART 201--LABELING

0
4. The authority citation for part 201 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.


Sec.  201.1  [Amended]

0
5. Amend Sec.  201.1(f) by removing ``Sec.  207.3(b)'' and adding in 
its place ``Sec.  207.1''.


Sec.  201.2  [Amended]

0
6. Amend Sec.  201.2 by removing the last sentence.

0
7. In Sec.  201.25 revise the first sentence of paragraph (c)(1) 
introductory text to read as follows:


Sec.  201.25  Bar code label requirements.

* * * * *
    (c) * * *
    (1) Each drug product described in paragraph (b) of this section 
must have a bar code that contains, at a minimum, the appropriate 
National Drug Code (NDC) number in a linear bar code that meets 
European Article Number/Uniform Code Council (EAN/UCC) or Health 
Industry Business Communications Council (HIBCC) standards or another 
standard or format that has been approved by the relevant Food and Drug 
Administration Center Director. * * *
* * * * *

0
8. Revise part 207 to read as follows:

PART 207--REQUIREMENTS FOR FOREIGN AND DOMESTIC ESTABLISHMENT 
REGISTRATION AND LISTING FOR HUMAN DRUGS, INCLUDING DRUGS THAT ARE 
REGULATED UNDER A BIOLOGICS LICENSE APPLICATION, AND ANIMAL DRUGS, 
AND THE NATIONAL DRUG CODE

Subpart A--General
Sec.
207.1 What definitions and interpretations of terms apply to this 
part?
207.3 Bulk drug substance.
207.5 What is the purpose of this part?
207.9 Who does this part cover?
207.13 Who is exempt from the registration and listing requirements?
Subpart B--Registration
207.17 Who must register?
207.21 When must initial registration information be provided?
207.25 What information is required for registration?
207.29 What are the requirements for reviewing and updating 
registration information?
Subpart C--National Drug Code
207.33 What is the National Drug Code (NDC), how is it assigned, and 
what are its requirements?
207.35 What changes require a new NDC?
207.37 What restrictions pertain to the use of the NDC?
Subpart D--Listing
207.41 Who must list drugs and what drugs must they list?
207.45 When, after initial registration of an establishment, must 
drug listing information be submitted?
207.49 What listing information must a registrant submit for a drug 
that it manufactures?
207.53 What listing information must a registrant submit for a drug 
that it repacks or relabels?
207.54 What listing information must a registrant submit for a drug 
that it salvages?
207.55 What additional drug listing information may FDA require?
207.57 What information must registrants submit when updating 
listing information and when?
Subpart E--Electronic Format for Registration and Listing
207.61 How is registration and listing information provided to FDA?
207.65 How can a waiver of the electronic submission requirement be 
obtained?
Subpart F--Miscellaneous
207.69 What are the requirements for an official contact and a 
United States agent?
207.77 What legal status is conferred by registration and listing?
207.81 What registration and listing information will FDA make 
available for public disclosure?


[[Page 60213]]


    Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360b, 371, 
374, 381, 393; 42 U.S.C. 262, 264, 271.

Subpart A--General


Sec.  207.1  What definitions and interpretations of terms apply to 
this part?

    The definitions and interpretations of terms in sections 201 and 
510 of the Federal Food, Drug, and Cosmetic Act apply to the terms used 
in this part, if not otherwise defined in this section. The following 
definitions apply to this part:
    Active pharmaceutical ingredient means any substance that is 
intended for incorporation into a finished drug product and is intended 
to furnish pharmacological activity or other direct effect in the 
diagnosis, cure, mitigation, treatment, or prevention of disease, or to 
affect the structure or any function of the body. Active pharmaceutical 
ingredient does not include intermediates used in the synthesis of the 
substance.
    Bulk drug substance, as referenced in sections 503A(b)(1)(A) and 
503B(a)(2) of the Federal Food, Drug, and Cosmetic Act, means the same 
as ``active pharmaceutical ingredient'' as defined in Sec.  207.1(b).
    Commercial distribution means any distribution of a human drug, 
except for investigational use under part 312 of this chapter, and any 
distribution of an animal drug or an animal feed bearing or containing 
an animal drug, except for investigational use under part 511 of this 
chapter. The term does not include internal or interplant transfer 
between registered establishments under common ownership and control, 
including a parent, subsidiary, or affiliate company. For foreign 
establishments that manufacture, repack, relabel, or salvage, or for 
foreign private label distributors, the term ``commercial 
distribution'' has the same meaning except the term does not include 
distribution of any drug that is neither imported nor offered for 
import into the United States.
    Content of labeling means:
    (1) For human prescription drugs that are subject to section 505 of 
the Federal Food, Drug, and Cosmetic Act or section 351 of the Public 
Health Service Act: The content of the prescription drug labeling (as 
specified in Sec. Sec.  201.56, 201.57, and 201.80 of this chapter), 
including all text, tables, and figures.
    (2) For human prescription drugs that are not subject to section 
505 of the Federal Food, Drug, and Cosmetic Act or section 351 of the 
Public Health Service Act: The labeling equivalent to the content of 
the prescription drug labeling (as specified in Sec. Sec.  201.56, 
201.57, and 201.80 of this chapter), including all text, tables, and 
figures.
    (3) For human over-the-counter (OTC) drugs: All text, tables, and 
figures including the drug facts labeling required by Sec.  201.66 of 
this chapter.
    (4) For animal drugs (including, but not limited to, drugs that are 
subject to section 512 of the Federal Food, Drug, and Cosmetic Act): 
The content of the labeling that accompanies the drug that is necessary 
to enable safe and proper administration of the drug (e.g., the 
labeling applicable to veterinary drugs specified in part 201 of this 
chapter), including all text, tables, and figures.
    Domestic for purposes of registration and listing under this part, 
when used to modify the term ``registrant,'' ``manufacturer,'' 
``repacker,'' ``relabeler,'' ``salvager,'' ``private label 
distributor,'' or ``establishment,'' refers to a registrant, 
manufacturer, repacker, relabeler, salvager, private label distributor, 
or establishment within any State or Territory of the United States, 
the District of Columbia, or the Commonwealth of Puerto Rico.
    Drug, for the purposes of registration and listing under this part, 
has the meaning given in section 201(g)(1) of the Federal Food, Drug, 
and Cosmetic Act.
    Establishment means a place of business under one management at one 
general physical location. The term includes, among others, independent 
laboratories that engage in control activities for a registered drug 
establishment (e.g., consulting laboratories), manufacturers of 
medicated feeds and of vitamin products that are drugs in accordance 
with section 201(g) of the Federal Food, Drug, and Cosmetic Act, human 
blood donor centers, and animal facilities used for the production or 
control testing of licensed biologicals, and establishments engaged in 
salvaging.
    Establishment registration number means the number assigned to the 
establishment, as identified by FDA, after the establishment 
registration required in this part.
    Finished drug product means a finished dosage form (e.g., tablet, 
capsule, or solution) that contains at least one active pharmaceutical 
ingredient, generally, but not necessarily, in association with other 
ingredients in finished package form suitable for distribution to 
pharmacies, hospitals, or other sellers or dispensers of the drug 
product to patients or consumers.
    Foreign for the purposes of registration and listing under this 
part:
    (1) When used to modify the term ``manufacturer,'' ``repacker,'' 
``relabeler,'' or ``salvager,'' refers to a manufacturer, repacker, 
relabeler, or salvager, who is located in a foreign country and who 
manufactures, repacks, relabels, or salvages a drug, or an animal feed 
bearing or containing a new animal drug, that is imported or offered 
for import into the United States.
    (2) When used to modify the term ``establishment'' refers to an 
establishment that is located in a foreign country and is engaged in 
the manufacture, repackaging, relabeling, or salvaging of any drug, or 
any animal feed bearing or containing a new animal drug, that is 
imported or offered for import into the United States.
    Importer means, for purposes of this part, a person in the United 
States that is an owner, consignee, or recipient, at the time of entry, 
of a foreign establishment's drug, or an animal feed bearing or 
containing a new animal drug, that is imported into the United States.
    Manufacture means each step in the manufacture, preparation, 
propagation, compounding, or processing of a drug or an animal feed 
bearing or containing a new animal drug. Manufacture includes the 
making by chemical, physical, biological, or other procedures or 
manipulations of a drug, or an animal feed bearing or containing a new 
animal drug, including control procedures applied to the final product 
or to any part of the process. Manufacture includes manipulation, 
sampling, testing, or control procedures applied to the final product 
or to any part of the process, including, for example, analytical 
testing of drugs for another registered establishment's drug. For 
purposes of this part, and in order to clarify the responsibilities of 
the entities engaged in different operations, the term manufacture is 
defined and used separately from the terms relabel, repackage, and 
salvage, although the term ``manufacture, preparation, propagation, 
compounding, or processing,'' as used in section 510 of the Federal 
Food, Drug, and Cosmetic Act, includes relabeling, repackaging, and 
salvaging activities.
    Manufacturer means a person who owns or operates an establishment 
that manufactures a drug or an animal feed bearing or containing a new 
animal drug. This term includes, but is not limited to, control 
laboratories, contract laboratories, contract manufacturers, contract 
packers, contract labelers, and other entities that manufacture a drug, 
or an animal feed bearing or containing a new animal drug, as defined 
in this paragraph. For purposes of this part,

[[Page 60214]]

and in order to clarify the responsibilities of the entities engaged in 
different operations, the term manufacturer is defined and used 
separately from the terms relabeler, repacker, and salvager, although 
the term ``manufacture, preparation, propagation, compounding, or 
processing,'' as used in section 510 of the Federal Food, Drug, and 
Cosmetic Act, includes the activities of relabelers, repackers, and 
salvagers. Repackers, relabelers, and salvagers are subject to the 
provisions of this part that are applicable to repackers, relabelers, 
and salvagers, but are not subject to the provisions of this part that 
are applicable to manufacturers. When not modified by ``domestic'' or 
``foreign,'' the term includes both domestic manufacturers and foreign 
manufacturers.
    Material change means any change in any drug listing information, 
as required under Sec. Sec.  207.49, 207.53, 207.54, 207.55, or 207.57 
except changes in format of labeling, labeling changes of an editorial 
nature, or inclusion of a bar code or initial inclusion of an NDC on 
the label.
    Outsourcing facility means a compounder that has elected to 
register with FDA under section 503B of the Federal Food, Drug, and 
Cosmetic Act and that meets all of the conditions of section 503B.
    Person who imports or offers for import means, for purposes of this 
part, the owner or exporter of a drug who consigns and ships a drug 
from a foreign country to the United States. This includes persons who 
send a drug to the United States by international mail or other private 
delivery service, but it does not include carriers who merely transport 
the drug.
    Private label distribution means commercial distribution of a drug 
under the label or trade name of a person who did not manufacture, 
repack, relabel, or salvage that drug.
    Private label distributor means, with respect to a particular drug, 
a person who did not manufacture, repack, relabel, or salvage the drug 
but under whose label or trade name the drug is commercially 
distributed.
    Registrant means any person that owns or operates an establishment 
that manufactures, repacks, relabels, or salvages a drug, and is not 
otherwise exempt from establishment registration requirements under 
section 510 of the Federal Food, Drug, and Cosmetic Act or this part.
    Relabel means to change the existing label or labels on a drug or 
drug package, or change or alter the existing labeling for a drug or 
drug package, without repacking the drug or drug package. This term 
does not include the addition or modification of information affixed 
solely for purposes of delivery to a customer, customer identification, 
and/or inventory management.
    Relabeler means a person who owns or operates an establishment that 
relabels a drug. When not modified by ``domestic'' or ``foreign,'' the 
term includes both domestic relabelers and foreign relabelers.
    Repack or repackage means the act of taking a finished drug product 
or unfinished drug from the container in which it was placed in 
commercial distribution and placing it into a different container 
without manipulating, changing, or affecting the composition or 
formulation of the drug.
    Repacker means a person who owns or operates an establishment that 
repacks a drug or drug package. When not modified by ``domestic'' or 
``foreign,'' the term includes both domestic repackers and foreign 
repackers.
    Representative sampling of advertisements means typical advertising 
material (including the promotional material described in Sec.  
202.1(l)(1) of this chapter, but excluding labeling as determined in 
Sec.  202.1(l)(2) of this chapter), that gives a balanced picture of 
the promotional claims used for the drug.
    Representative sampling of any other labeling means typical 
labeling material (including the labeling material described in Sec.  
202.1(l)(2) of this chapter, but excluding labels and package inserts) 
that gives a balanced picture of the promotional claims used for the 
drug.
    Salvage means the act of segregating out those finished drug 
products that may have been subjected to improper storage conditions 
(such as extremes in temperature, humidity, smoke, fumes, pressure, 
age, or radiation) for the purpose of returning the products to the 
marketplace and includes applying manufacturing controls such as those 
required by current good manufacturing practice in parts 210 and 211 of 
this chapter.
    Salvager means a person who owns or operates an establishment that 
engages in salvaging. When not modified by ``domestic'' or ``foreign,'' 
the term includes both domestic and foreign salvagers.
    Unfinished drug means an active pharmaceutical ingredient either 
alone or together with one or more other ingredients but does not 
include finished drug products.


Sec.  207.3  Bulk drug substance.

    Bulk drug substance, as referenced in sections 503A(b)(1)(A) and 
503B(a)(2) of the Federal Food, Drug, and Cosmetic Act, previously 
defined in Sec.  207.3(a)(4), means the same as ``active pharmaceutical 
ingredient'' as defined in Sec.  207.1(b).


Sec.  207.5  What is the purpose of this part?

    Establishment registration information helps FDA identify who is 
manufacturing, repacking, relabeling, and salvaging drugs and where 
those operations are performed. Drug listing information gives FDA a 
current inventory of drugs manufactured, repacked, relabeled, or 
salvaged for commercial distribution. Both types of information 
facilitate implementation and enforcement of the Federal Food, Drug, 
and Cosmetic Act and are used for many important public health 
purposes.


Sec.  207.9  Who does this part cover?

    (a) Except as provided in paragraph (b) of this section, this part 
applies to:
    (1) Domestic manufacturers, domestic repackers, domestic relabelers 
and domestic salvagers, not exempt under section 510(g) of the Federal 
Food, Drug, and Cosmetic Act or Sec.  207.13, regardless of whether 
their drugs enter interstate commerce;
    (2) Foreign manufacturers, foreign repackers, foreign relabelers 
and foreign salvagers, not exempt under section 510(g) of the Federal 
Food, Drug, and Cosmetic Act or Sec.  207.13;
    (3) Private label distributors, because they must have labeler 
codes;
    (4) Establishments engaged in the manufacture, repacking, 
relabeling, or salvaging of human drugs regulated under a biologics 
license application (BLA). These establishments are subject to the 
requirements of this part unless they are required to register and list 
such drugs as human blood or blood products under part 607 of this 
chapter and do not engage in activities that would otherwise require 
them to register and list under this part.
    (5) Establishments engaged in the manufacture (as defined in Sec.  
1271.3(e) of this chapter) of human cells, tissues, and cellular and 
tissue-based products (HCT/Ps) (as defined in Sec.  1271.3(d) of this 
chapter) that, under Sec.  1271.20 of this chapter, are also drugs 
regulated under section 351 of the Public Health Service Act or section 
505 of the Federal Food, Drug, and Cosmetic Act. These establishments 
must register and list those HCT/Ps following the procedures described 
in this part.
    (b) This part does not apply to owners and operators of 
establishments that collect or process human whole blood

[[Page 60215]]

and blood products unless the establishment also manufactures, repacks, 
or relabels other drugs. For purposes of this paragraph (b), human 
whole blood and blood products do not include plasma derivatives such 
as albumin, Immune Globulin, Factor VIII and Factor IX, and recombinant 
versions of plasma derivatives or animal derived plasma derivatives, or 
bulk product substances such as fractionation intermediates or pastes. 
Establishments that collect or process human whole blood and blood 
products as well as establishments involved in testing of human whole 
blood and blood products must register and list under part 607 of this 
chapter. Manufacturers of licensed devices and manufacturers of 
licensed biological products used in a licensed device must register 
and list under part 607 of this chapter.
    (c) This part does not apply to establishments that solely 
manufacture, prepare, propagate, compound, assemble, or process medical 
devices. Registration and listing regulations for such establishments 
are codified in part 807 of this chapter.


Sec.  207.13  Who is exempt from the registration and listing 
requirements?

    Except as provided in Sec.  207.13(l), the following classes of 
persons are exempt from registration and drug listing in accordance 
with section 510(g) of the Federal Food, Drug, and Cosmetic Act or 
because FDA has determined, under section 510(g)(5) of the Federal 
Food, Drug, and Cosmetic Act, that their registration is not necessary 
for the protection of the public health. This exemption is limited to 
establishment registration and drug listing requirements and does not 
relieve a person from other statutory or regulatory obligations.
    (a)(1) Pharmacies that:
    (i) Operate in conformance with all applicable local laws 
regulating the practice of pharmacy and medicine, including all 
applicable local laws regulating the dispensing of prescription drugs;
    (ii) Regularly engage in dispensing prescription drugs upon a valid 
prescription by practitioners licensed by law to administer these drugs 
to patients under their professional care; and
    (iii) Do not manufacture, repack, relabel, or salvage drugs other 
than in the regular course of their business of dispensing or selling 
drugs at retail.
    (2) The exemption in this paragraph (a) is limited to pharmacies 
located in any State as defined in section 201(a)(1) of the Federal 
Food, Drug, and Cosmetic Act.
    (b)(1) Hospitals, clinics, other health care entities, and public 
health agencies that:
    (i) Operate establishments in conformance with all applicable local 
laws regulating the practice of pharmacy and medicine, including all 
applicable local laws regulating the dispensing of prescription drugs;
    (ii) Regularly engage in dispensing prescription drugs, other than 
human whole blood or blood products, upon a valid order or prescription 
by practitioners licensed by law to administer these drugs to patients 
under their professional care; and
    (iii) Do not manufacture, repack, relabel, or salvage drugs other 
than in the regular course of their practice of pharmacy, including 
dispensing.
    (2) The exemption in this paragraph (b) is limited to hospitals, 
clinics, other health care entities, and public health agencies located 
in any State as defined in section 201(a)(1) of the Federal Food, Drug, 
and Cosmetic Act.
    (c) Individuals or establishments under contract, agreement, or 
other arrangement with a registered establishment and engaged solely in 
recovering cells or tissues and sending the recovered cells or tissues 
to the registered establishment to become components of a biological 
product are exempt from registration and listing under this part unless 
FDA determines that drug establishment registration and listing is 
necessary for the protection of the public health.
    (d) Practitioners who are licensed by law to prescribe or 
administer drugs and who manufacture, repack, relabel, or salvage drugs 
solely for use in their professional practice.
    (e) Manufacturers, repackers, relabelers, or salvagers who 
manufacture, repack, relabel, or salvage drugs solely for use in 
research, teaching, or chemical analysis and not for sale.
    (f) Manufacturers, repackers, and relabelers of harmless inactive 
ingredients such as excipients, colorings, flavorings, emulsifiers, 
lubricants, preservatives, or solvents that become components of drugs.
    (g) Manufacturers, repackers, relabelers, or salvagers of Type B or 
Type C medicated feeds, except for persons who manufacture, repack, 
relabel, or salvage Type B or Type C medicated feeds starting from 
Category II, Type A medicated articles for which a medicated feed mill 
license approved under part 515 of this chapter is required. This 
exemption also does not apply to persons that would otherwise be 
required to register (such as manufacturers, repackers, relabelers, or 
salvagers of certain free-choice feeds, as defined in Sec.  510.455 of 
this chapter, or certain liquid feeds, as defined in Sec.  558.5 of 
this chapter, where the specifications and/or formulas are not 
published and a medicated feed mill license is required). All 
manufacturers, repackers, relabelers, or salvagers of Type B or Type C 
medicated feeds are exempt from listing.
    (h) Any manufacturer, repacker, relabeler, or salvager of a virus, 
serum, toxin, or analogous product intended for the treatment of 
domestic animals who holds an unsuspended and unrevoked license issued 
by the Secretary of Agriculture under the animal virus-serum-toxin law 
of March 4, 1913 (37 Stat. 832 (21 U.S.C. 151 et seq.)), provided that 
this exemption from registration applies only to the manufacturer, 
repacker, relabeler, or salvager of that animal virus, serum, toxin, or 
analogous product.
    (i) Carriers, in their receipt, carriage, holding, or delivery of 
drugs in the usual course of business as carriers.
    (j) Foreign establishments whose drugs are imported or offered for 
import into the United States must comply with the establishment 
registration and listing requirements of this part unless exempt under 
this section or unless:
    (1) Their drugs enter a foreign trade zone and are re-exported 
without having entered U.S. commerce, or
    (2) Their drugs are imported in conformance with section 801(d)(3) 
of the Federal Food, Drug, and Cosmetic Act.
    (k) Entities that are registered with FDA as outsourcing facilities 
and that compound drugs in conformance with section 503B of the Federal 
Food, Drug, and Cosmetic Act.
    (l) The exemptions provided in paragraphs (a) through (k) of this 
section do not apply to such persons if they:
    (1) Manufacture (as defined in Sec.  207.1(b)), repack, relabel, or 
salvage compounded positron emission tomography drugs as defined in 
section 201(ii) of the Federal Food, Drug, and Cosmetic Act;
    (2) Manufacture (as defined in Sec.  600.3(u) of this chapter) a 
human biological product subject to licensing under section 351 of the 
Public Health Service Act; or
    (3) Engage in activities that would otherwise require them to 
register under this part.

Subpart B--Registration


Sec.  207.17  Who must register?

    (a) Unless exempt under section 510(g) of the Federal Food, Drug, 
and Cosmetic Act or this part, all

[[Page 60216]]

manufacturers, repackers, relabelers, and salvagers must register each 
domestic establishment that manufactures, repacks, relabels, or 
salvages a drug, or an animal feed bearing or containing a new animal 
drug, and each foreign establishment that manufactures, repacks, 
relabels, or salvages a drug, or an animal feed bearing or containing a 
new animal drug, that is imported or offered for import into the United 
States. When operations are conducted at more than one establishment 
and common ownership and control among all the establishments exists, 
the parent, subsidiary, or affiliate company may submit registration 
information for all establishments.
    (b) Private label distributors who do not also manufacture, repack, 
relabel, or salvage drugs are not required to register under this part. 
FDA will accept registration or listing information submitted by a 
private label distributor only if it is acting as an authorized agent 
for and submitting information that pertains to an establishment that 
manufactures, repacks, relabels, or salvages drugs.


Sec.  207.21  When must initial registration information be provided?

    (a) Registrants must register each domestic establishment no later 
than 5 calendar days after beginning to manufacture, repack, relabel, 
or salvage a drug or an animal feed bearing or containing a new animal 
drug at such establishment.
    (b) Registrants must register each foreign establishment before a 
drug or an animal feed bearing or containing a new animal drug 
manufactured, repacked, relabeled, or salvaged at the establishment is 
imported or offered for import into the United States.


Sec.  207.25  What information is required for registration?

    Registrants must provide the following information:
    (a) Name of the owner or operator of each establishment; if a 
partnership, the name of each partner; if a corporation, the name of 
each corporate officer and director, and the place of incorporation;
    (b) Each establishment's name, physical address, and telephone 
number(s);
    (c) All name(s) of the establishment, including names under which 
the establishment conducts business or names by which the establishment 
is known;
    (d) Registration number of each establishment, if previously 
assigned by FDA;
    (e) A Unique Facility Identifier in accordance with the system 
specified under section 510 of the Federal Food, Drug, and Cosmetic 
Act.
    (f) All types of operations performed at each establishment;
    (g) Name, mailing address, telephone number, and email address of 
the official contact for the establishment, as provided in Sec.  
207.69(a); and
    (h) Additionally, with respect to foreign establishments subject to 
registration, the name, mailing address, telephone number, and email 
address must be provided for:
    (1) The United States agent, as provided in Sec.  207.69(b);
    (2) Each importer in the United States of drugs manufactured, 
repacked, relabeled, or salvaged at the establishment that is known to 
the establishment; and
    (3) Each person who imports or offers for import such drug to the 
United States.


Sec.  207.29  What are the requirements for reviewing and updating 
registration information?

    (a) Expedited updates. Registrants must update their registration 
information no later than 30 calendar days after:
    (1) Closing or selling an establishment;
    (2) Changing an establishment's name or physical address; or
    (3) Changing the name, mailing address, telephone number, or email 
address of the official contact or the United States agent. A 
registrant, official contact, or United States agent may notify FDA 
about a change of information for the designated official contact or 
United States agent, but only a registrant is permitted to designate a 
new official contact or United States agent.
    (b) Annual review and update of registration information. 
Registrants must review and update all registration information 
required under Sec.  207.25 for each establishment.
    (1) The first review and update must occur during the period 
beginning on October 1 and ending December 31 of the year of initial 
registration, if the initial registration occurs prior to October 1. 
Subsequent reviews and updates must occur annually, during the period 
beginning on October 1 and ending December 31 of each calendar year.
    (2) The updates must reflect all changes that have occurred since 
the last annual review and update.
    (3) If no changes have occurred since the last registration, 
registrants must certify that no changes have occurred.

Subpart C--National Drug Code


Sec.  207.33  What is the National Drug Code (NDC), how is it assigned, 
and what are its requirements?

    (a) What is the NDC for a drug and what products must have unique 
NDCs? The NDC for a drug is a numeric code. Each finished drug product 
or unfinished drug subject to the listing requirements of this part 
must have a unique NDC to identify its labeler, product, and package 
size and type.
    (b) What is the format of an NDC? (1) Except as described in 
paragraph (b)(4) of this section, the NDC must consist of 10 or 11 
digits, divided into three segments as follows:
    (i) The first segment of the NDC is the labeler code and consists 
of 4, 5, or 6 digits. The labeler code is assigned by FDA.
    (ii) The second segment of the NDC is the product code and consists 
of 3 or 4 digits, as specified in paragraphs (b)(2) and (3) of this 
section.
    (iii) The third segment of the NDC is the package code and consists 
of 1 or 2 digits as specified in paragraphs (b)(2) and (3) of this 
section. The package code identifies the package size and type of the 
drug and differentiates between different quantitative and qualitative 
attributes of the product packaging.
    (2) The following combinations of labeler code, product code and 
package code character lengths are permissible:
    (i) If a labeler code is either 5 or 6 digits in length, it may be 
combined with:
    (A) A product code consisting of 4 digits and a package code 
consisting of 1 digit for a total NDC length of 10 or 11 digits (5-4-1 
or 6-4-1), or
    (B) A product code consisting of 3 digits and a package code 
consisting of 2 digits for a total NDC length of 10 or 11 digits (5-3-2 
or 6-3-2).
    (ii) If a labeler code is 4 digits in length, it may be combined 
only with a product code consisting of 4 digits and a package code 
consisting of 2 digits for a total NDC length of 10 digits (4-4-2).
    (3) A registrant or private label distributor with a given labeler 
code must use only one Product-Package Code configuration (e.g., a 3-
digit product code combined with a 2-digit package code or a 4-digit 
product code combined with a 1-digit package code). This single 
configuration must be used in all NDCs that include the given labeler 
code that are reserved in accordance with Sec.  207.33(d)(3) or listed 
in accordance with Sec.  207.49 or Sec.  207.53.
    (4) An alternatively formatted NDC that is approved for use by the 
relevant Center Director may be used for the following HCT/Ps if they 
are minimally

[[Page 60217]]

manipulated: Hematopoietic stem/progenitor cells derived from 
peripheral and cord blood, and lymphocytes collected from peripheral 
blood.
    (c) Who must obtain an NDC labeler code and how is the code 
assigned and updated? (1) Each person who engages in manufacturing, 
repacking, relabeling, or private label distribution of a drug subject 
to listing under this part must apply for an NDC labeler code, by 
providing the following information:
    (i) The name, physical address, email address, and other contact 
information FDA may request, of the person for whom the NDC labeler 
code is requested;
    (ii) The type(s) of activities (e.g., manufacture or repacking) in 
which the person requesting the NDC labeler code engages with respect 
to human drugs; and
    (iii) The type(s) of drug(s) (human, animal, or both, and 
prescription, nonprescription, or both) to which the NDC labeler code 
will be applied.
    (2) Each person who is assigned an NDC labeler code must update the 
information submitted under paragraph (c)(1)of this section within 30 
calendar days after any change to that information.
    (d) How is an NDC proposed for assignment by FDA, when is an NDC 
assigned by FDA, and how can a proposed NDC be reserved? (1) An NDC is 
proposed for assignment by FDA when it is submitted for the first time 
with listing information in accordance with Sec.  207.49 or Sec.  
207.53, as applicable.
    (i) Each manufacturer, repacker, or relabeler must propose for 
assignment by FDA an NDC that includes its own labeler code for each 
package size and type of drug that it manufactures, repacks, or 
relabels for commercial distribution.
    (ii) In addition, if a drug is distributed under the trade name or 
label of a private label distributor, the manufacturer, repacker, or 
relabeler must also propose for assignment by FDA an NDC that includes 
the labeler code of the private label distributor under whose trade 
name or label the drug is distributed, for each package size and type 
so distributed.
    (2) If a proposed NDC conforms to the requirements of this section 
and is not reserved for a different drug or was not previously assigned 
to a different drug, FDA will assign the NDC to a drug when it receives 
listing information required for that drug under Sec.  207.49 or Sec.  
207.53.
    (3) A manufacturer, repacker, relabeler, or private label 
distributor may voluntarily reserve a proposed NDC for a drug, before 
the drug is listed, by submitting the following information:
    (i) A proposed NDC that conforms to the requirements of this 
section;
    (ii) The established name of the active ingredient(s) and the 
strength of each active ingredient in the drug; and
    (iii) In the case of a finished drug product, the dosage form, and 
route of administration.
    (4) If the required information is submitted and the proposed NDC 
is properly formatted and not already assigned or reserved, FDA will 
reserve the proposed NDC for a period of 2 years from the date of 
submission. If the drug for which the proposed NDC is reserved is not 
listed in accordance with Sec.  207.49 or Sec.  207.53 during such 2-
year period, the reservation of the proposed NDC will lapse. FDA may 
also cancel the reservation of a proposed NDC at any time on the 
request of the person whose labeler code is included in the proposed 
NDC.
    (e) How must the information be submitted to us? The information 
described in paragraphs (c) and (d) of this section must be submitted 
electronically unless FDA grants a waiver under Sec.  207.65.


Sec.  207.35  What changes require a new NDC?

    (a) Once an NDC has been assigned by FDA, the registrant must 
propose a new and unique NDC for a drug when there is a change, after 
the drug is initially marketed, to any of the information identified in 
paragraphs (b) and (c) of this section. A new NDC must be proposed to 
FDA for assignment through an updated listing in accordance with Sec.  
207.57.
    (b) The proposed new NDC must include a new product code when there 
is a change to any of the following information:
    (1) The drug's established name or proprietary name, if any;
    (2) Any active pharmaceutical ingredient or the strength of any 
active pharmaceutical ingredient;
    (3) The dosage form;
    (4) A change in the drug's status, between prescription and 
nonprescription, or for animal drugs, between prescription, 
nonprescription, or veterinary feed directive (VFD) status;
    (5) A change in the drug's intended use between human and animal; 
or
    (6) The drug's distinguishing characteristics such as size, shape, 
color, code imprint, flavor, and scoring (if any).
    (c) When there is a change only to the package size or type, 
including the immediate unit-of-use container, if any, the proposed new 
NDC must include only a new package code and retain the existing 
product code unless all available package codes have already been 
combined with the existing product code in NDCs assigned by FDA.


Sec.  207.37  What restrictions pertain to the use of the NDC?

    (a) A product may be deemed to be misbranded if an NDC is used:
    (1) To represent a different drug than the drug for which the NDC 
has been assigned, as described in Sec.  207.33;
    (2) To denote or imply FDA approval of a drug; or
    (3) On products that are not subject to parts 207, 607 of this 
chapter, or 1271 of this chapter, such as dietary supplements and 
medical devices.
    (b) If marketing is resumed for a discontinued drug, and no changes 
have been made to the drug that would require a new NDC under Sec.  
207.35, the drug must have the same NDC that was assigned to it as 
described in Sec.  207.33, before marketing was discontinued.

Subpart D--Listing


Sec.  207.41  Who must list drugs and what drugs must they list?

    (a) Each registrant must list each drug that it manufactures, 
repacks, relabels, or salvages for commercial distribution. Each 
domestic registrant must list each such drug regardless of whether the 
drug enters interstate commerce. When operations are conducted at more 
than one establishment, and common ownership and control exists among 
all the establishments, the parent, subsidiary, or affiliate company 
may submit listing information for any drug manufactured, repacked, 
relabeled, or salvaged at any such establishment. A drug manufactured, 
repacked, or relabeled for private label distribution must be listed in 
accordance with paragraph (c) of this section.
    (b) Registrants must provide listing information for each drug in 
accordance with the listing requirements described in Sec. Sec.  
207.49, 207.53, and 207.54 that correspond to the activity or 
activities they engage in for that drug.
    (c)(1) For both animal and human drugs, each registrant must list 
each drug it manufactures, repacks, or relabels for commercial 
distribution under the trade name or label of a private label 
distributor using an NDC that includes such private label distributor's 
labeler code.
    (2) Additionally, in the case of human drugs, each registrant must 
list each human drug it manufactures, repacks, or relabels using an NDC 
that includes the registrant's own labeler code, regardless of whether 
the drug is commercially distributed under the registrant's own label 
or trade name or under the label

[[Page 60218]]

or trade name of a private label distributor.


Sec.  207.45  When, after initial registration of an establishment, 
must drug listing information be submitted?

    For each drug being manufactured, repacked, relabeled, or salvaged 
for commercial distribution at an establishment at the time of initial 
registration, drug listing information must be submitted no later than 
3 calendar days after the initial registration of the establishment.


Sec.  207.49  What listing information must a registrant submit for a 
drug it manufactures?

    (a) Each registrant must provide the following listing information 
for each drug it manufactures for commercial distribution.
    (1) The appropriate NDC(s), as described in Sec.  207.33, that 
include all package code variations. In the case of human drugs, the 
appropriate NDC(s) submitted under this paragraph include the 
registrant's labeler code. In the case of animal drugs, the appropriate 
NDC(s) submitted under this paragraph include the registrant's labeler 
code, except that when the drug is manufactured for commercial 
distribution under the trade name or label of a private label 
distributor, the appropriate NDC(s) for animal drugs include the 
private label distributor's labeler code;
    (2) Package type and volume information corresponding to the 
package code segment of the NDC;
    (3) The listed drug's established name and proprietary name, if 
any;
    (4) The name and quantity of each active pharmaceutical ingredient 
in the listed drug;
    (5) The name of each inactive ingredient in the listed drug, along 
with any assertions of confidentiality associated with individual 
inactive ingredients;
    (6) The dosage form;
    (7) The drug's approved U.S. application number, if any;
    (8) The drug type (e.g., as applicable, finished vs. unfinished, 
human vs. animal, prescription vs. nonprescription);
    (9) In the case of an unfinished drug, the number assigned to the 
Drug Master File or Veterinary Master File, if any, that describes the 
manufacture of the drug;
    (10) For each drug that is subject to the imprinting requirements 
of part 206 of this chapter including products that are exempted under 
Sec.  206.7(b), the drug's size, shape, color, scoring, and code 
imprint (if any);
    (11) The route or routes of administration of the drug;
    (12) For each drug bearing an NDC:
    (i) The name and Unique Facility Identifier of the establishment 
where the registrant who lists the drug manufactures it and the type of 
operation performed on the drug at that establishment, and
    (ii) The name and Unique Facility Identifier of every other 
establishment where manufacturing is performed for the drug and the 
type of operation performed at each such establishment. This includes 
all establishments involved in the production of each unfinished drug 
received by the registrant for use in the production of the drug being 
listed. The names, Unique Facility Identifiers, and type of operations 
for establishments involved in production of each unfinished drug 
received by the registrant for use in the production of the drug being 
listed may be provided by including the properly assigned and listed 
NDC for such unfinished drug.
    (13) The schedule of the drug under section 202 of the Controlled 
Substances Act, if applicable;
    (14) Advertisements:
    (i) A representative sampling of advertisements for a human 
prescription drug that is not subject to section 505 of the Federal 
Food, Drug, and Cosmetic Act or section 351 of the Public Health 
Service Act;
    (ii) If FDA requests it, for good cause, a copy of all 
advertisements for a human prescription drug that is not subject to 
section 505 of the Federal Food, Drug, and Cosmetic Act or section 351 
of the Public Health Service Act, including those advertisements 
described in Sec.  202.1(l)(1) of this chapter. Such advertisements 
must be submitted within 30 calendar days after FDA's request.
    (15) For drugs bearing the NDC(s) reported under paragraph (a)(1) 
of this section, except those drugs manufactured exclusively for 
private label distribution and not distributed under the registrant's 
own name and label, provide the following labeling, as applicable:
    (i) Human prescription drugs. All current labeling except that only 
one representative container or carton label need be submitted where 
differences exist only in the quantity of contents statement or the bar 
code. This labeling submission must include the content of labeling, as 
defined in Sec.  207.1(b).
    (ii) Human nonprescription drugs. (A) For each human 
nonprescription drug subject to section 505 of the Federal Food, Drug, 
and Cosmetic Act or section 351 of the Public Health Service Act, all 
current labeling, except that only one representative container or 
carton label need be submitted where differences exist only in the 
quantity of contents statement or the bar code. This labeling 
submission must include the content of labeling, as defined in Sec.  
207.1(b).
    (B) For each human nonprescription drug not subject to section 505 
of the Federal Food, Drug, and Cosmetic Act or section 351 of the 
Public Health Service Act, the current label (except that only one 
representative container or carton label need be submitted where 
differences exist only in the quantity of contents statement or the bar 
code), the package insert (if any), and a representative sampling of 
any other labeling. This labeling submission must include the content 
of labeling as defined in section Sec.  207.1(b).
    (iii) Animal drugs. (A) For each animal drug that is subject to 
section 512 of the Federal Food, Drug, and Cosmetic Act, which 
includes, but is not limited to, new animal drugs that have been 
approved, conditionally approved, or indexed under sections 512, 571, 
or 572 of the Federal Food, Drug, and Cosmetic Act, a copy of all 
current labeling (except that only one representative container or 
carton label need be submitted where differences exist only in the 
quantity of contents statement), including the content of labeling as 
defined in Sec.  207.1(b);
    (B) For all other animal drugs, a copy of the current label (except 
that only one representative container or carton label need be 
submitted where differences exist only in the quantity of contents 
statement), the package insert, the content of labeling as defined in 
Sec.  207.1(b), and a representative sampling of any other labeling;
    (iv) All other listed drugs. For all other listed drugs, including 
unfinished drugs, the label (if any), except that only one 
representative label need be submitted where differences exist only in 
the quantity of contents statement.
    (16) Listing submissions described in Sec.  207.41(c)(2) for human 
drugs manufactured for private label distribution must include all 
information specified in Sec.  207.49(a)(2) through (14) and:
    (i) The appropriate NDC(s) (as described in Sec.  207.33) that 
include the private label distributor's labeler code and all package 
code variations;
    (ii) The name, mailing address, telephone number, and email address 
of the private label distributor; and
    (iii) For drugs bearing the NDC(s) reported under paragraph 
(a)(16)(i) of this section, labeling as described in paragraph (a)(15) 
of this section that accompanies the private label distributor's 
product.

[[Page 60219]]

    (b) Additionally, each registrant is requested, but not required, 
to provide the following information for each human drug it 
manufactures for commercial distribution:
    (1) The drug's over-the-counter monograph reference, if any; and
    (2) The date on which the drug was or will be introduced into 
commercial distribution.


Sec.  207.53  What listing information must a registrant submit for a 
drug that it repacks or relabels?

    Each registrant must provide the following listing information for 
each drug it repacks or relabels:
    (a) NDC. The appropriate NDC(s), as described in Sec.  207.33, that 
include the registrant's labeler code and all package code variations;
    (b) Source NDC. The NDC assigned to each finished drug received by 
the registrant for repacking or relabeling, with the exception of 
medical gases. Each such NDC must be associated with the corresponding 
NDC(s) for repacked or relabeled drugs, reported under paragraph (a) of 
this section.
    (c) Name and Unique Facility Identifier. For each drug identified 
by an NDC reported under paragraph (a) of this section, the name and 
Unique Facility Identifier of every establishment where repacking or 
relabeling is performed for the drug and the type of operation 
(repacking vs. relabeling) performed at each such establishment.
    (d) Labeling. For each drug identified by an NDC reported under 
paragraph (a) of this section, except those human drugs repacked or 
relabeled exclusively for private label distribution and not 
distributed under the registrant's own name and label, provide the 
following:
    (1) Human prescription drugs. All current labeling for the repacked 
or relabeled drug except that only one representative container or 
carton label need be submitted where differences exist only in the 
quantity of contents statement or the bar code. This labeling 
submission must include the content of labeling, as defined in section 
Sec.  207.1(b).
    (2) Human nonprescription drugs. (i) For each human nonprescription 
drug subject to section 505 of the Federal Food, Drug, and Cosmetic Act 
or section 351 of the Public Health Service Act, all current labeling, 
except that only one representative container or carton label need be 
submitted where differences exist only in the quantity of contents 
statement or the bar code. This labeling submission must include the 
content of labeling, as defined in Sec.  207.1(b).
    (ii) For each human nonprescription drug not subject to section 505 
of the Federal Food, Drug, and Cosmetic Act or section 351 of the 
Public Health Service Act, the current label (except that only one 
representative container or carton label need be submitted where 
differences exist only in the quantity of contents statement or the bar 
code), the package insert (if any), and a representative sampling of 
any other labeling. This labeling submission must include the content 
of labeling as defined in Sec.  207.1(b).
    (3) Animal drugs. (i) For each animal drug that is subject to 
section 512 of the Federal Food, Drug, and Cosmetic Act, which includes 
but is not limited to, new animal drugs that have been approved, 
conditionally approved, or indexed under sections 512, 571, or 572 of 
the Federal Food, Drug, and Cosmetic Act, a copy of all current 
labeling (except that only one representative container or carton label 
need be submitted where differences exist only in the quantity of 
contents statement), including the content of labeling as defined in 
Sec.  207.1(b);
    (ii) For all other animal drugs, a copy of the current label 
(except that only one representative container or carton label need be 
submitted where differences exist only in the quantity of contents 
statement), the package insert, the content of labeling as defined in 
Sec.  207.1(b), and a representative sampling of any other labeling;
    (4) All other. For all other listed drugs, including unfinished 
drugs, the label (if any), except that only one representative label 
need be submitted where differences exist only in the quantity of 
contents statement.
    (e) Advertisements. (1) A representative sampling of advertisements 
for a human prescription drug that is not subject to section 505 of the 
Federal Food, Drug, and Cosmetic Act or section 351 of the Public 
Health Service Act;
    (2) If we request it for good cause, a copy of all advertisements 
for a particular drug described in paragraph (e)(1) of this section, 
including advertisements described in Sec.  202.1(l)(1) of this 
chapter. Such advertisements must be submitted within 30 calendar days 
after our request.
    (f) Private label distributor products. A listing submission for a 
human drug distributed by a private label distributor described in 
Sec.  207.41(c)(2) must include information specified in Sec.  
207.53(b) through (e) as applicable and:
    (1) The appropriate NDC(s) (as described in Sec.  207.33) that 
include the private label distributor's labeler code and all package 
code variations;
    (2) The name, mailing address, telephone number, and email address 
of the private label distributor; and
    (3) For drugs bearing the NDC(s) reported under paragraph (f)(1) of 
this section, labeling as described in paragraphs (d)(1) through (4) of 
this section, as applicable, that accompanies the private label 
distributor's product.


Sec.  207.54  What listing information must a registrant submit for a 
drug that it salvages?

    A registrant who also relabels or repacks a drug that it salvages 
must list the drug it relabels or repacks in accordance with Sec.  
207.53 rather than in accordance with this section. A registrant who 
performs only salvaging with respect to a drug must provide the 
following listing information for that drug.
    (a) The NDC assigned to the drug immediately before the drug is 
received by the registrant for salvaging;
    (b) The lot number and expiration date of the salvaged drug 
product; and
    (c) The name and Unique Facility Identifier for each establishment 
where the registrant salvages the drug.


Sec.  207.55  What additional drug listing information may FDA require?

    For a particular listed drug, upon our request, the registrant must 
briefly state the basis for its belief that the drug is not subject to 
section 505 or 512 of the Federal Food, Drug, and Cosmetic Act or 
section 351 of the Public Health Service Act.


Sec.  207.57  What information must registrants submit when updating 
listing information and when?

    Registrants must review and update listing information at a 
minimum, as follows:
    (a) Registrants must provide listing information at the time of 
annual establishment registration for any drug manufactured, repacked, 
relabeled, or salvaged by them for commercial distribution that has not 
been listed previously.
    (b) Registrants must review and update their drug listing 
information each June and December. When doing so, registrants must:
    (1)(i) Provide listing information, in accordance with Sec. Sec.  
207.49, 207.53, and 207.54, for any drug manufactured, repacked, 
relabeled, or salvaged by them for commercial distribution that has not 
been previously listed;
    (ii) Submit the date that they discontinued the manufacture, 
repacking, relabeling or salvaging for commercial distribution of a 
listed drug and provide the expiration date of the

[[Page 60220]]

last lot manufactured, repacked, relabeled, or salvaged;
    (iii) Submit the date that they resumed the manufacture, repacking, 
or relabeling for commercial distribution of a drug previously 
discontinued, and provide any required listing information not 
previously submitted; and
    (iv) Submit any material changes in any information previously 
submitted pursuant to Sec. Sec.  207.49, 207.53, 207.54, or other 
relevant sections of this part; or
    (2) For each listed drug, certify that no changes subject to 
reporting under paragraph (b)(1)(iv) of this section have occurred if 
no such changes have occurred since the last review and update. If a 
drug is discontinued and FDA has received the information required 
under paragraph (b)(1)(ii) of this section, no further certifications 
are necessary for the discontinued drug. After initial electronic 
listing, registrants may satisfy the listing update requirement with 
respect to unchanged listing information by making a single ``no 
changes'' certification during the annual registration update under 
Sec.  207.29(b) applicable to all of the registrant's listed drugs for 
which no changes have been made since the previous annual registration 
update.
    (c) Registrants are encouraged to submit listing information for 
every drug subject to listing under this part prior to commercial 
distribution and are encouraged to update listing information at the 
time of any change affecting information previously submitted.

Subpart E--Electronic Format for Registration and Listing


Sec.  207.61  How is registration and listing information provided to 
FDA?

    (a) Electronic format. (1) Except as provided in Sec.  207.65, all 
information submitted under this part must be transmitted to FDA in 
electronic format by using our electronic drug registration and listing 
system, in a form that we can process, review, and archive. We may 
periodically issue guidance on how to provide registration and listing 
information in electronic format (specifying for example method of 
transmission, media, file formats, preparation, and organization of 
files).
    (2) Information provided in electronic format must comply with part 
11 of this chapter, except as follows:
    (i) Advertisements and labeling, including the content of labeling, 
required under this part are exempt from the requirements in Sec.  
11.10(a), (c) through (h), and (k) of this chapter and the 
corresponding requirements in Sec.  11.30 of this chapter.
    (ii) All other information submitted under this part is exempt from 
the requirements in Sec.  11.10(b), (c), and (e) of this chapter and 
the corresponding requirements in Sec.  11.30 of this chapter.
    (b) English language. Drug establishment registration and drug 
listing information must be provided in the English language. The 
content of labeling must be provided at a minimum in the English 
language. Where Sec.  201.15(c) of this chapter permits product 
labeling solely in a foreign language, the content of labeling must be 
submitted in that language along with an accurate English translation.


Sec.  207.65  How can a waiver of the electronic submission requirement 
be obtained?

    (a) All information submitted under this part must be transmitted 
to FDA electronically in accordance with Sec.  207.61(a) unless FDA has 
granted a request for waiver of this requirement prior to the date on 
which submission of such information is due. Submission of a request 
for waiver does not excuse timely compliance with the registration and 
listing requirements. FDA will grant a waiver request if FDA determines 
that the use of electronic means for submission of registration and 
listing information is not reasonable for the registrant making the 
waiver request.
    (b) Waiver requests under this section must be submitted in writing 
and must include the specific reasons why electronic submission is not 
reasonable for the registrant and a U.S. telephone number and mailing 
address where FDA can contact the registrant. All waiver requests must 
be sent to: SPL Coordinator, U.S. Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 32, Silver Spring, MD 20993.
    (c) If FDA grants the waiver request, FDA may limit its duration 
and will specify terms of the waiver and provide information on how to 
submit establishment registration, drug listings, other information, 
and updates, as applicable.

Subpart F--Miscellaneous


Sec.  207.69  What are the requirements for an official contact and a 
United States agent?

    (a) Official contact. Registrants subject to the registration 
requirements of this part must designate an official contact for each 
establishment. The official contact is responsible for:
    (1) Ensuring the accuracy of registration and listing information; 
and
    (2) Reviewing, disseminating, routing, and responding to all 
communications from FDA including emergency communications.
    (b) United States agent. Registrants of foreign establishments 
subject to this part must designate a single United States agent. The 
United States agent must reside or maintain a place of business in the 
United States and may not be a mailbox, answering machine or service, 
or other place where a person acting as the United States agent is not 
physically present. The United States agent is responsible for:
    (1) Reviewing, disseminating, routing, and responding to all 
communications from FDA including emergency communications;
    (2) Responding to questions concerning those drugs that are 
imported or offered for import to the United States;
    (3) Assisting FDA in scheduling inspections; and
    (4) If FDA is unable to contact a foreign registrant directly or 
expeditiously, FDA may provide the information and/or documents to the 
United States agent. FDA's providing information and/or documents to 
the United States agent is equivalent to providing the same information 
and/or documents to the foreign registrant.


Sec.  207.77  What legal status is conferred by registration and 
listing?

    (a) Registration of an establishment or listing of a drug does not 
denote approval of the establishment, the drug, or other drugs of the 
establishment, nor does it mean that a product may be legally marketed. 
Any representation that creates an impression of official approval or 
that a drug is approved or is legally marketable because of 
registration or listing is misleading and constitutes misbranding.
    (b) FDA's acceptance of registration and listing information, 
inclusion of a drug in our database of drugs, or assignment of an NDC 
does not denote approval of the establishment or the drug or any other 
drugs of the establishment, nor does it mean that the drug may be 
legally marketed. Any representation that creates the impression that a 
drug is approved or is legally marketable because it appears in our 
database of drugs, has been assigned or displays an NDC, or the 
establishment has been assigned an establishment registration number or 
Unique Facility Identifier is misleading and constitutes misbranding. 
Failure to comply with Sec.  207.37 may also constitute misbranding.
    (c) Neither registration nor listing constitutes a determination by 
FDA that a product is a drug as defined by section 201(g)(1) of the 
Federal Food, Drug, and Cosmetic Act. Registration or listing may, 
however, be evidence that a

[[Page 60221]]

facility intends to or does manufacture, repack, relabel, distribute, 
or salvage drugs or that a product is intended to be a drug.


Sec.  207.81  What registration and listing information will FDA make 
available for public disclosure?

    (a) Except as provided in paragraphs (b) and (c) of this section, 
the following information will be available for public disclosure, upon 
request or at FDA's discretion:
    (1) All establishment registration information, and
    (2) After a drug is marketed, information obtained under Sec.  
207.33, Sec.  207.49, Sec.  207.53, Sec.  207.54, or Sec.  207.57.
    (b) Unless such information is publicly available or FDA finds that 
confidentiality would be inconsistent with protection of the public 
health, FDA will not make publicly available:
    (1) Any information submitted under Sec.  207.55 as the basis upon 
which it has been determined that a particular drug is not subject to 
section 505 or 512 of the Federal Food, Drug, and Cosmetic Act or 
section 351 of the Public Health Service Act,
    (2) The names of any inactive ingredients submitted under Sec.  
207.49(a)(4) for which the registrant makes a valid assertion of 
confidentiality under Sec.  20.61 of this chapter or other provision of 
law, or
    (3) Drug listing information obtained under Sec.  207.33(d)(3), 
Sec.  207.49(a)(9) and (12), Sec.  207.53(b) and (c), or Sec.  
207.54(a) or (c).
    (c) FDA may determine, in limited circumstances and on a case-by-
case basis, that it would be consistent with the protection of the 
public health and the Freedom of Information Act to exempt from public 
disclosure specific information identified in paragraph (a) of this 
section.

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

0
9. The authority citation for part 314 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 356a, 
356b, 356c, 356e, 371, 374, 379e, 379k-1.

0
10. In Sec.  314.81, revise paragraph (b)(3)(iv) to read as follows:


Sec.  314.81  Other postmarketing reports.

* * * * *
    (b) * * *
    (3) * * *
    (iv) Withdrawal of approved drug product from sale. (a) Within 30 
calendar days of the withdrawal of an approved drug from sale, 
applicants who are manufacturers, repackers, or relabelers subject to 
part 207 of this chapter must submit the following information about 
the drug, in accordance with the applicable requirements described in 
Sec. Sec.  207.61 and 207.65:
    (1) The National Drug Code (NDC);
    (2) The identity of the drug by established name and by proprietary 
name, if any;
    (3) The new drug application number or abbreviated application 
number;
    (4) The date on which the drug is expected to be no longer in 
commercial distribution. FDA requests that the reason for withdrawal of 
the drug from sale be included with the information.
    (b) Within 30 calendar days of the withdrawal of an approved drug 
from sale, applicants who are not subject to part 207 of this chapter 
must submit the information listed in paragraphs (b)(3)(iv)(a)(1) 
through (4) of this section. The information must be submitted either 
electronically or in writing to the Drug Registration and Listing 
Office, Food and Drug Administration, Center for Drug Evaluation and 
Research.
    (c) Reporting under paragraph (b)(3)(iv)(a) of this section 
constitutes compliance with the requirements of Sec.  207.57 of this 
chapter to update drug listing information with respect to the 
withdrawal from sale.
* * * * *


Sec.  314.125  [Amended]

0
11. Amend Sec.  314.125 in paragraph (b)(11) by removing the words ``or 
processed''.

PART 514--NEW ANIMAL DRUG APPLICATIONS

0
12. The authority citation for part 514 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 354, 356a, 360b, 
360ccc, 371, 379e, 381.

0
13. In Sec.  514.111 add paragraph (a)(12) to read as follows:


Sec.  514.111  Refusal to approve an application.

    (a) * * *
    (12) The drug will be produced in whole or in part in an 
establishment that is not registered and not exempt from registration 
under section 510 of the Federal Food, Drug, and Cosmetic Act and part 
207 of this chapter.
* * * * *

PART 515--MEDICATED FEED MILL LICENSE

0
14. The authority citation for part 515 continues to read as follows:

    Authority: 21 U.S.C. 360b, 371.


Sec.  515.10  [Amended]

0
15. In Sec.  515.10(b)(8), remove the phrase ``Sec. Sec.  207.20 and 
207.21'' and add in its place the phrase ``part 207''.

PART 601--LICENSING

0
16. The authority citation for part 601 continues to read as follows:

    Authority: 15 U.S.C. 1451-1561; 21 U.S.C. 321, 351, 352, 353, 
355, 356b, 360, 360c-360f, 360h-360j, 371, 374, 379e, 381; 42 U.S.C. 
216, 241, 262, 263, 264; sec. 122, Pub. L. 105-115, 111 Stat. 2322 
(21 U.S.C. 355 note).

0
17. In Sec.  601.2, add paragraph (f) to read as follows:


Sec.  601.2  Applications for biologics licenses; procedures for 
filing.

* * * * *
    (f) Withdrawal from sale of approved biological products. A holder 
of a biologics license application (BLA) must report to FDA, in 
accordance with the requirements of Sec. Sec.  207.61 and 207.65, the 
withdrawal from sale of an approved biological product. The information 
must be submitted to FDA within 30 working days of the biological 
product's withdrawal from sale. The following information must be 
submitted: The holder's name; product name; BLA number; the National 
Drug Code; and the date on which the product is expected to be no 
longer in commercial distribution. The reason for the withdrawal of the 
biological product is requested but not required to be submitted.

PART 607--ESTABLISHMENT REGISTRATION AND PRODUCT LISTING FOR 
MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS AND LICENSED 
DEVICES

0
18. The authority citation for part 607 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 371, 374, 
381, 393; 42 U.S.C. 262, 264, 271.

0
19. Revise the heading for part 607 to read as set forth above.

0
20. Add Sec.  607.1 to subpart A to read as follows:


Sec.  607.1  Scope.

    (a) This part establishes establishment registration and product 
listing requirements for manufacturers of human blood and blood 
products.
    (b) This part establishes establishment registration and product 
listing requirements for manufacturers of products that meet the 
definition of a device under the Federal Food, Drug, and Cosmetic Act 
and that are licensed under section 351 of the Public Health

[[Page 60222]]

Service Act, as well as licensed biological products used in the 
manufacture of a licensed device.

0
21. In Sec.  607.3 revise the second sentence in paragraph (b) and add 
paragraphs (k) and (l) to read as follows:


Sec.  607.3  Definitions.

* * * * *
    (b) * * * For the purposes of this part only, blood and blood 
product also means those products that meet the definition of a device 
under the Federal Food, Drug, and Cosmetic Act and that are licensed 
under section 351 of the Public Health Service Act, as well as licensed 
biological products used in the manufacture of a licensed device.
* * * * *
    (k) Importer means a person in the United States that is an owner, 
consignee, or recipient, at the time of entry, of a foreign 
establishment's blood product that is imported into the United States.
    (l) Foreign for the purpose of registration and listing under this 
part when used to modify the term ``establishment'' refers to an 
establishment that is located in a foreign country and is the site 
where a blood product that is imported or offered for import into the 
United States was manufactured.

0
22. Revise Sec.  607.7 to read as follows:


Sec.  607.7  Establishment registration and product listing of blood 
banks and other firms manufacturing human blood and blood products.

    All owners or operators of establishments that engage in the 
manufacturing of blood products are required to register, pursuant to 
section 510 of the Federal Food, Drug, and Cosmetic Act. Registration 
and listing of blood products must comply with this part. Registration 
does not permit any blood bank or similar establishment to ship blood 
products in interstate commerce.

0
23. In Sec.  607.20 revise the first sentence in paragraph (c) to read 
as follows:


Sec.  607.20  Who must register and submit a blood product list.

* * * * *
    (c) Except in the case of licensed device manufacturers, no 
registration fee is required. * * *

0
24. In Sec.  607.21 revise the last sentence to read as follows:


Sec.  607.21  Times for establishment registration and blood product 
listing.

    * * * Owners or operators of all establishments so engaged must 
register annually between October 1 and December 31 and must update 
their blood product listing every June and December.

0
25. Revise Sec.  607.22 to read as follows:


Sec.  607.22  How to register establishments and list blood products.

    (a) Initial and subsequent registrations and product listings must 
be submitted electronically through the Blood Establishment 
Registration and Product Listing system, or any future superseding 
electronic system. This information must be submitted in accordance 
with part 11 of this chapter, except for the requirements in Sec.  
11.10(b), (c), and (e), and the corresponding requirements in Sec.  
11.30. All information submitted under this part must be transmitted to 
FDA electronically unless FDA has granted a request for waiver of this 
requirement prior to the date on which the information is due. 
Submission of a request for waiver does not excuse timely compliance 
with the registration and listing requirements. FDA will grant a waiver 
request if FDA determines that the use of electronic means for 
submission of registration and listing information is not reasonable 
for the registrant making the waiver request.
    (b) Waiver requests under this section must be submitted in writing 
and must include the specific reasons why electronic submission is not 
reasonable for the registrant and a U.S. telephone number and mailing 
address where FDA can contact the registrant. All waiver requests must 
be sent to the Director of FDA's Center for Biologics Evaluation and 
Research through the Document Control Center (see addresses in Sec.  
600.2).
    (c) If FDA grants the waiver request, FDA may limit its duration 
and will specify terms of the waiver and provide information on how to 
submit establishment registration, drug listings, other information, 
and updates, as applicable.

0
26. Revise Sec.  607.25 to read as follows:


Sec.  607.25  Information required for establishment registration and 
blood product listing.

    (a) The Blood Establishment Registration and Product Listing system 
requires furnishing or confirming registration information required by 
the Federal Food, Drug, and Cosmetic Act. This information includes the 
name and street address of the establishment, including post office 
code; a registration number if previously assigned by FDA and a Unique 
Facility Identifier in accordance with the system specified under 
section 510 of the Federal Food, Drug, and Cosmetic Act; all trade 
names used by the establishment; the kind of ownership or operation 
(that is, individually owned partnership, or corporation); and the name 
of the owner or operator of such establishment. The term ``name of the 
owner or operator'' must include, in the case of a partnership, the 
name of each partner and, in the case of a corporation, the name and 
title of each corporate officer and director and the name of the State 
of incorporation. The information required must be given separately for 
each establishment, as defined in Sec.  607.3(c).
    (b) The following information must also be provided:
    (1) A list of blood products by established name as defined in 
section 502(e) of the Federal Food, Drug, and Cosmetic Act and by 
proprietary name, if any, which are being manufactured for commercial 
distribution at the identified establishment and which have not been 
included in any list previously submitted to FDA through the Blood 
Establishment Registration and Product Listing system or any future 
superseding electronic system.
    (2) For each blood product so listed that is subject to section 351 
of the Public Health Service Act, the license number of the 
manufacturer issued by the Center for Biologics Evaluation and 
Research, Food and Drug Administration.
    (3) For each blood product listed, the registration number if 
previously assigned by FDA and the Unique Facility Identifier of the 
parent establishment. An establishment not owned, operated, or 
controlled by another firm or establishment is its own parent 
establishment.

0
27. In Sec.  607.26 revise the first sentence to read as follows:


Sec.  607.26  Amendments to establishment registration.

    Changes in individual ownership, corporate or partnership 
structure, location, or blood product handling activity must be 
submitted electronically through the Blood Establishment Registration 
and Product Listing system, or any future superseding electronic 
system, as an amendment to registration within 5 calendar days of such 
changes. * * *

0
28. In Sec.  607.30 revise the introductory text of paragraph (a) to 
read as follows:


Sec.  607.30  Updating blood product listing information.

    (a) After submission of the initial blood product listing 
information, every person who is required to list blood products under 
Sec.  607.20 must submit electronically through the Blood Establishment 
Registration and Product

[[Page 60223]]

Listing system, or any future superseding electronic system, at a 
minimum once in June and December of every year, the following 
information:
* * * * *

0
29. Revise Sec.  607.35 to read as follows:


Sec.  607.35  Blood product establishment registration number.

    An establishment registration number will be assigned to each blood 
product establishment registered in accordance with this part.

0
30. Revise Sec.  607.37 to read as follows:


Sec.  607.37  Public disclosure of establishment registration and blood 
product listing information.

    (a) Except as provided in paragraph (b) of this section, all 
registration and listing information obtained under Sec. Sec.  607.25, 
607.26, and 607.30 will be made available for public disclosure through 
the Center for Biologics Evaluation and Research (CBER) Blood 
Establishment Registration Database Web site by using the CBER 
electronic Web-based application or by going in person to the Food and 
Drug Administration, Division of Freedom of Information Public Reading 
Room (see addresses in Sec.  20.120(a) of this chapter).
    (b) FDA may find, in limited circumstances and on a case-by-case 
basis, that it would be consistent with the protection of the public 
health to exempt from public disclosure specific listing information 
obtained under Sec.  607.25 or Sec.  607.30.
    (c) Other requests for information regarding blood establishment 
registrations and blood product listings should be directed to the Food 
and Drug Administration, Center for Biologics Evaluation and Research 
Office of Communication, Outreach, and Development, 10903 New Hampshire 
Ave., Bldg. 71, Rm. 3103, Silver Spring, MD 20993-0002.

0
31. Revise Sec.  607.39 to read as follows:


Sec.  607.39  Misbranding by reference to establishment registration, 
validation of registration, or to registration number.

    Registration of an establishment, validation of registration, or 
assignment of a registration number does not in any way denote approval 
of the firm or its products nor does it mean that the products may be 
legally marketed. Any representation that creates an impression of 
official approval because of establishment registration, validation of 
registration, or possession of a registration number is misleading and 
constitutes misbranding.

0
32. In Sec.  607.40 revise paragraphs (d) introductory text and (d)(3) 
and add paragraph (e) to read as follows:


Sec.  607.40  Establishment registration and blood product listing 
requirements for foreign blood product establishments.

* * * * *
    (d) Each foreign establishment required to register under paragraph 
(a) of this section must submit the name, address, telephone number, 
and email address of its United States agent as part of its initial and 
updated registration information in accordance with subpart B of this 
part. Each foreign establishment must designate only one United States 
agent.
* * * * *
    (3) The foreign establishment or the United States agent must 
report changes in the United States agent's name, address, telephone 
number, or email address to FDA within 30 calendar days of the change.
    (e) Each foreign establishment required to register under paragraph 
(a) of this section must register and list blood products using the 
Blood Establishment Registration and Product Listing system, or any 
superseding electronic system, unless FDA waives the electronic 
submission requirement in accordance with Sec.  607.22.

0
33. In Sec.  607.65 add paragraph (g) to read as follows:


Sec.  607.65  Exemptions for blood product establishments.

* * * * *
    (g) Persons who engage solely in the production of any plasma 
derivative, including, but not limited to, albumin, Immune Globulin, 
Factor VIII and Factor IX, bulk product substances such as 
fractionation intermediates or pastes, or recombinant versions of 
plasma derivatives or animal derived plasma derivatives. These persons 
must register and list under part 207 of this chapter.

0
34. Add subpart E, consisting of Sec.  607.80, to part 607 to read as 
follows:

Subpart E--Establishment Registration and Product Listing Of 
Licensed Devices


Sec.  607.80  Applicability of part 607 to licensed devices.

    Manufacturers of products that meet the definition of a device 
under the Federal Food, Drug, and Cosmetic Act and that are licensed 
under section 351 of the Public Health Service Act, as well as licensed 
biological products used in the manufacture of a licensed device, must 
register and list following the procedures under this part, with 
respect to their manufacture of those products, unless otherwise noted 
in this section.

PART 1271--HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED 
PRODUCTS

0
35. The authority citation for part 1271 continues to read as follows:

    Authority:  42 U.S.C. 216, 243, 263a, 264, 271.


Sec.  1271.1  [Amended]

0
36. Amend Sec.  1271.1 in paragraphs (a) and (b)(2) by removing 
``207.20(f)'' and adding in its place ``207.9(a)(5)''; in paragraph (a) 
by removing the term ``a unified'' and adding in its place the term 
``an electronic''; and in paragraph (b)(2) by removing the phrase ``in 
subpart B of this part'' and adding in its place the phrase ``in part 
207 (if a drug and/or biological product) of this chapter or part 807 
(if a device) of this chapter''.

0
37. In Sec.  1271.3 add paragraphs (mm) and (nn) to read as follows:


Sec.  1271.3  How does FDA define important terms in this part?

* * * * *
    (mm) Importer means a company or individual in the United States 
that is the owner, consignee, or recipient, at the time of entry, of 
the foreign establishment's HCT/P that is imported into the United 
States.
    (nn) United States agent means a person residing or maintaining a 
place of business in the United States whom a foreign establishment 
designates as its agent. This definition excludes mailboxes, answering 
machines or services, or other places where an individual acting as the 
foreign establishment's agent is not physically present.


Sec.  1271.20  [Amended]

0
38. Amend Sec.  1271.20 by removing ``207.20(f)'' and adding in its 
place ``207.9(a)(5)'' and by removing the phrase ``subparts B, C, and D 
of this part'' and adding in its place ``subparts C and D of this 
part''.

0
39. Revise Sec.  1271.22 to read as follows:


Sec.  1271.22  How do I register and submit an HCT/P list?

    (a) You must use the electronic registration and listing system at 
http://www.fda.gov/cber/tissue/tisreg.htm in accordance with Sec.  
1271.25 for:
    (1) Establishment registration,
    (2) HCT/P listings, and
    (3) Updates of registration and HCT/P listing.
    (b) FDA will periodically issue guidance on recommended procedures 
for providing registration and listing information in electronic format 
(for

[[Page 60224]]

example, method of transmission, media, file formats, preparation, and 
organization of files).
    (c) You must provide the information under paragraph (a) of this 
section in accordance with part 11 of this chapter, except for the 
requirements in Sec.  11.10(b), (c), and (e) and the corresponding 
requirements in Sec.  11.30.

0
40. Add Sec.  1271.23 to subpart B to read as follows:


Sec.  1271.23  How is a waiver from the electronic format requirements 
requested?

    (a) You may request a waiver from the requirement in Sec.  1271.22 
that information must be provided to FDA in electronic format. 
Submission of a request for waiver does not excuse timely compliance 
with the registration and listing requirements. FDA will grant a waiver 
request if FDA determines that the use of electronic means for 
submission of registration and listing information is not reasonable 
for the registrant making the waiver request.
    (b) Waiver requests under this section must be submitted in writing 
and must include the specific reasons why electronic submission is not 
reasonable for the registrant and a U.S. telephone number and mailing 
address where FDA can contact the registrant. Waiver requests may be 
sent to the Center for Biologics Evaluation and Research (CBER), 
Document Control Center (see addresses in Sec.  600.2 of this chapter).
    (c) If FDA grants the waiver request, FDA may limit its duration 
and will specify terms of the waiver and provide information on how to 
submit establishment registration, listings, other information, and 
updates, as applicable.

0
41. In Sec.  1271.25 revise paragraphs (a) introductory text and (a)(2) 
and (3), add paragraphs (a)(5) and (6), revise paragraph (c)(4), and 
add paragraph (d) to read as follows:


Sec.  1271.25  What information is required for establishment 
registration and HCT/P listing?

    (a) Your establishment registration must include:
* * * * *
    (2) Each physical location, including the street address, telephone 
number, email address, and the postal service ZIP code of the 
establishment;
    (3) The name, address, telephone number, email address, and title 
of the reporting official;
* * * * *
    (5) Each foreign establishment must also submit the name, address, 
telephone number, and email address of each importer that is known to 
the establishment, and the name of each person who imports or offers 
for import such HCT/P to the United States for purposes of importation; 
and
    (6) Each foreign establishment must also submit the name, address, 
telephone number, and email address of its United States agent.
    (i) The United States agent must reside or maintain a place of 
business in the United States.
    (ii) Upon request from FDA, the United States agent must assist FDA 
in communications with the foreign establishment, respond to questions 
concerning the foreign establishment's products that are imported or 
offered for import into the United States, and assist FDA in scheduling 
inspections of the foreign establishment. If the Agency is unable to 
contact the foreign establishment directly or expeditiously, FDA may 
provide information or documents to the United States agent, and such 
an action is equivalent to providing the same information or documents 
to the foreign establishment.
    (iii) The foreign establishment or the United States agent must 
report changes in the United States agent's name, address, telephone 
number, or email address to FDA within 30 calendar days of the change.
* * * * *
    (c) * * *
    (4) Any material change in any information previously submitted. 
Material changes include any change in registration and listing 
information, submitted, such as whether the HCT/P meets the criteria 
set out in Sec.  1271.10.
    (d) If your HCT/P is described under Sec.  1271.20 and is regulated 
under a BLA, you must submit the information required under part 207 of 
this chapter using the procedures under subpart E of part 207.

0
42. Revise Sec.  1271.26 to read as follows:


Sec.  1271.26  When must I amend my establishment registration?

    If the ownership or location of your establishment changes, or if 
there is a change in the United States agent's name, address, telephone 
number, or email address, you must submit an amendment to registration 
within 30 calendar days of the change.

    Dated: August 22, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-20471 Filed 8-30-16; 8:45 am]
 BILLING CODE 4164-01-P


