
[Federal Register Volume 77, Number 58 (Monday, March 26, 2012)]
[Notices]
[Pages 17484-17487]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-7136]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0742]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Registration of 
Producers of Drugs and Listing of Drugs in Commercial Distribution

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by April 
25, 2012.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-0045. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: Juanmanuel Vilela, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-7651, 
juanmanuel.vilela@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Registration of Producers of Drugs and Listing of Drugs in Commercial 
Distribution--21 CFR Part 207--(OMB Control Number 0910-0045)--
Extension

    Requirements for drug establishment registration and drug listing 
are set forth in section 510 of the Federal Food, Drug, and Cosmetic 
Act (the FD&C Act) (21 U.S.C. 360); section 351 of the Public Health 
Service Act; and part 207 (21 CFR part 207). Fundamental to FDA's 
mission to protect the public health is the collection of this 
information, which is used for important activities such as postmarket 
surveillance for serious adverse drug reactions, inspection of drug 
manufacturing and processing facilities, and monitoring of drug 
products imported into the United States. Comprehensive, accurate, and 
up-to-date information is critical to conducting these activities with 
efficiency and effectiveness.
    Under section 510 of the FD&C Act, FDA is authorized to establish a 
system for registration of producers of drugs and for listing of drugs 
in commercial distribution. To implement section 510 of the FD&C Act, 
FDA issued part 207.\1\ Under current Sec.  207.20, manufacturers, 
repackers, and relabelers that engage in the manufacture, preparation, 
propagation, compounding, or processing of human or veterinary drugs 
and biological products, including bulk drug substances and bulk drug 
substances for prescription compounding, and drug premixes as well as 
finished dosage forms, whether prescription or over-the-counter, are 
required to register their establishment. In addition, manufacturers, 
repackers, and relabelers are required to submit a listing of every 
drug or biological product in commercial distribution. Owners or 
operators of establishments that distribute under their own label or 
trade name a drug product manufactured by a registered establishment 
are not required either to register or list. However, distributors may 
elect to submit drug listing information in lieu of the registered 
establishment that manufactures the drug product. Foreign drug

[[Page 17485]]

establishments must also comply with the establishment registration and 
product listing requirements if they import or offer for import their 
products into the United States.
---------------------------------------------------------------------------

    \1\ This document addresses the information collection in 
current part 207. In the Federal Register of August 29, 2006 (the 
2006 proposed rule) (71 FR 51276), FDA proposed to revise part 207. 
The proposed revisions would reorganize, consolidate, clarify, and 
modify current regulations concerning who must register 
establishments and list, and describes when and how to register and 
list and what information must be submitted for registration and 
listing. In addition, the proposal would make certain changes to the 
National Drug Code (NDC) system and would require the appropriate 
NDC number to appear on the labels for drugs subject to the listing 
requirements. The proposed regulations generally also require the 
electronic submission of all registration and most listing 
information. The 2006 proposed rule requested comments on the 
information collection for revised part 207. When the proposal is 
finalized, the information collection for a revised part 207 will 
replace the information collection in this document.
---------------------------------------------------------------------------

    Under current Sec.  207.21, establishments, both domestic and 
foreign, must register with FDA within 5 days after beginning the 
manufacture of drugs or biologicals, or within 5 days after the 
submission of a drug application or biological license application 
(BLA). In addition, establishments must register annually. Changes in 
individual ownership, corporate or partnership structure, location, or 
drug-handling activity must be submitted as amendments to registration 
under current Sec.  207.26 within 5 days of such changes. Under Sec.  
207.20(b), private label distributors may request their own labeler 
code and elect to submit drug listing information to FDA. In such 
instances, at the time of submitting or updating drug listing 
information, private label distributors must certify to the registered 
establishment that manufactured, prepared, propagated, compounded or 
processed (which includes, among other things, repackaging and 
relabeling) the listed drug that the drug listing submission was made. 
Establishments must, within 5 days of beginning the manufacture of 
drugs or biologicals, submit to FDA a listing for every drug or 
biological product in commercial distribution at that time. Private 
label distributors may elect to submit to FDA a listing of every drug 
product they place in commercial distribution. Registered 
establishments must submit to FDA drug product listing for those 
private label distributors who do not elect to submit listing 
information.
    Under Sec.  207.25, product listing information submitted to FDA by 
domestic and foreign manufacturers must, depending on the type of 
product being listed, include any new drug application (NDA) number or 
biological establishment license number, copies of current labeling and 
a sampling of advertisements, a quantitative listing of the active 
ingredient for each drug or biological product not subject to an 
approved application or license, the NDC number, and any drug 
imprinting information.
    In addition to the product listing information required, FDA may 
also require, under Sec.  207.31, a copy of all advertisements and a 
quantitative listing of all ingredients for each listed drug or 
biological product not subject to an approved application or license; 
the basis for a determination, by the establishment, that a listed drug 
or biological product is not subject to marketing or licensing approval 
requirements; and a list of certain drugs or biological products 
containing a particular ingredient. FDA may also request, but not 
require, the submission of a qualitative listing of the inactive 
ingredients for all listed drugs or biological products, and a 
quantitative listing of the active ingredients for all listed drugs or 
biological products subject to an approved application or license.
    Under Sec.  207.30, establishments must update their product 
listing information every June and December or, at the discretion of 
the establishment, when any change occurs. These updates must include 
the following information: (1) A listing of all drug or biological 
products introduced for commercial distribution that have not been 
included in any previously submitted list; (2) all drug or biological 
products formerly listed for which commercial distribution has been 
discontinued; (3) all drug or biological products for which a notice of 
discontinuance was submitted and for which commercial distribution has 
been resumed; and (4) any material change in any information previously 
submitted. No update is required if no changes have occurred since the 
previously submitted list.
    Historically, drug establishment registration and drug listing 
information have been submitted in paper form 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) (collectively 
referred to as FDA Forms).
    Changes in the FD&C Act resulting from enactment of the Food and 
Drug Administration Amendments Act of 2007 (Pub. L. 110-85) (FDAAA) 
require that drug establishment registration and drug listing 
information be submitted electronically unless a waiver is granted. 
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 provided that drug listing information 
be submitted in the form and manner prescribed by FDA. Section 224 of 
FDAAA, which amends section 510(p) of the FD&C Act, now expressly, 
requires electronic drug listing in addition to drug establishment 
registration. In certain cases, if it is unreasonable to expect a 
person to submit registration and listing information electronically, 
FDA may grant a waiver from the electronic format requirement.
    In the Federal Register of June 1, 2009 (74 FR 26248), FDA 
announced the availability of a guidance for industry entitled 
``Providing Regulatory Submissions in Electronic Format--Drug 
Establishment Registration and Drug Listing'' (the 2009 guidance). The 
document provides guidance to industry on 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 addition to the information that previously was collected by the 
FDA Forms, the guidance addresses electronic submission of other 
required information as follows:
     For registered foreign drug establishments, the name, 
address, and telephone number of its U.S. agent (Sec.  207.40(c));
     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. An importer does not 
include the consumer or patient who ultimately purchases, receives, or 
is administered the drug, unless the foreign establishment ships the 
drug directly to the consumer or the patient) (section 510(i)(1)(A) of 
the FD&C Act); and
     The name of each person who imports or offers 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 
their drug into the United States) (section 510(i)(1)(A) of the FD&C 
Act).
    FDA also recommends the voluntary submission of the following 
additional information, when applicable:
     To facilitate correspondence between foreign 
establishments and FDA, the email address for the U.S. 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 (e.g., the registrant, establishments, U.S. 
agent, importer);
     The NDC product code for the source drug that is repacked 
or relabeled;

[[Page 17486]]

     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 
the registrant's business relationship with an establishment, or an 
inactive ingredient.
    In addition to the collection of information, there is additional 
burden for the following activities:
     Preparing a standard operating procedure (SOP) for the 
electronic submission of drug establishment registration and drug 
listing information;
     Creating the SPL file, including accessing and reviewing 
the technical specifications and instructional documents provided by 
FDA (accessible at http://www.fda.gov/oc/datacouncil/spl.html);
     Reviewing and selecting appropriate terms and codes used 
to create the SPL file (accessible at http://www.fda.gov/oc/datacouncil/spl.html);
     Obtaining the digital certificate used with FDA's 
electronic submission gateway and uploading the SPL file for submission 
(accessible at http://www.fda.gov/esg/default.htm); and
     Requests for waivers from the electronic submission 
process as described in the draft guidance.
    When FDA published the 2009 guidance on submitting establishment 
registration and drug listing information in electronic format, the 
Agency also amended its burden estimates for OMB control number 0910-
0045 to include the additional burden for collection of information 
that had not been submitted using the FDA Forms, and to create and 
upload the SPL file. The amended burden estimates included the one-time 
preparation of an SOP for creating and uploading the SPL file. Although 
most firms will already have prepared an SOP for the electronic 
submission of drug establishment registration and drug listing 
information, each year additional firms will need to create an SOP. As 
provided in table 2 of this document, FDA estimates that approximately 
1,000 firms will have to expend a one-time burden to prepare, review, 
and approve an SOP, and the Agency estimates that it will take 40 hours 
per recordkeeper to create 1,000 new SOPs for a total of 40,000 hours. 
The information collection requirements of the Drug Listing and 
Establishment Registration regulations have been grouped according to 
the information collection areas of the regulations.
    In the Federal Register of October 24, 2011 (76 FR 65730), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one comment.

Comment

    The comment raised two issues and asked for several procedural 
clarifications. The first issue raised suggested that the burden to 
industry might be greater than the 4.5-hour average provided in the 
estimate. The next issue questioned the process by which FDA issued a 
guidance to address the electronic submissions process without changing 
the regulation that still describes a paper submission process, which 
would have allowed for public comment on that change. The comment then 
sought several procedural clarifications on: (1) How to submit changes 
in ownership of an establishment, (2) how to select a business 
function, (3) how to ensure that an establishment is represented 
consistently between a vendor's registration and the client's drug 
establishment registration, (4) how to link an importer with a 
particular product, (5) how to list bulk tablets that will be imported 
for packaging, and (6) how to certify to the registered establishment 
that the private label distributor has listed the product.

Response

    FDA acknowledges that the 2009 guidance is different from the 
process described in the current part 207. As was stated in the Federal 
Register notice and as acknowledged by the commenter, the current 
regulation predates the electronic process and describes a paper-based 
submission process. FDA is in the process of rewriting part 207, and 
published the draft version for public comment in 2006. Afterward, the 
FDAAA mandated the electronic submission of drug establishment and drug 
product information. The 2009 guidance was created to address the 
mandate of FDAAA. The 2006 proposed rule will be modified appropriately 
to address the FDAAA mandates as well. With regards to the estimated 
burden, FDA collaborated with members of industry and international 
health information data standards organizations to arrive at the 
current process and estimates for the burden of gathering, assembling, 
and submitting data. The estimates are considered to be averages that 
will vary up or down per individual respondent.
    The following paragraphs are intended to clarify one of the 
commenter's issues mentioned previously in this document:
    1. Changes to the establishment name, registrant name, or other 
registration information can be made by submitting an updated 
registration submission via SPL. Changes in corporate ownership or 
officers that do not affect names, addresses, or the DUNS number(s) for 
a registered establishment should be made with Dun and Bradstreet. That 
data is then referenced as needed by FDA using the DUNS number. 
Information about submitting SPL can be found at the link at the end of 
the FDA response. It should be noted that changes in ownership may also 
require the submission of updates to listing information, labeler code 
name and DUNS, and application data for NDAs, abbreviated new drug 
applications (ANDAs), BLAs, new animal drug applications (NADAs), and 
abbreviated new animal drug applications (ANADAs).
    2. For selecting a business operation, a current list of valid 
business functions and their associated codes can be found at the link 
at the end of this response. Please note that if more than one business 
function apply, a registrant should select all that apply and include 
them in the registration SPL.
    3. FDA has implemented an automated validation of all drug product 
listing submissions to ensure that each establishment referenced in the 
product listing is registered under the same business operation. For 
example, a product listing SPL that references a particular facility as 
a packer of the product will be rejected if that establishment has not 
chosen Pack as a business operation in its registration. FDA expects 
vendors and clients to communicate this information directly to each 
other and, if necessary, coordinate their submissions in order to avoid 
issues with this validation.
    4. The importer information is submitted via the registration of 
the foreign establishment. Any product listing referencing that foreign 
establishment should therefore provide the necessary link from importer 
to product. Information about submitting SPL can be found at the link 
at the end of the FDA response.
    5. A product listing for bulk tablets intended for further 
processing or packaging should be listed using the SPL product/document 
type of Bulk Ingredient and a marketing category of Drug for Further 
Processing. Information about submitting SPL can be found at the link 
at the end of the FDA response.
    6. For finished dosage forms, appearance in the NDC Directory is 
proof of submission of listing. Note that unfinished products and 
active pharmaceutical ingredient listings will not appear in the NDC 
Directory.

[[Page 17487]]

    Instructions and SPL resources may be found on the SPL Resources 
Web page at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
            Activity                 Number of     responses per   Total  annual    burden per     Total  hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
New registrations, including new              39           14.72             574             4.5           2,583
 labeler codes requests.........
Annual updates of registration             3,256            2.99           9,735             4.5          43,808
 information....................
New drug listings...............           1,567            6.57          10,295             4.5          46,328
New listings for private label               146           10.06           1,469             4.5           6,611
 distributor....................
June and December updates of all           1,677           11.21          18,799             4.5          84,596
 drug listing information.......
Waiver requests.................               1               1               1               1               1
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............         183,927
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
 Activity resulting from section                     Number of                    Average burden
    510(p) of the FD&C Act as        Number of      records per    Total annual         per         Total hours
        amended by FDAAA           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
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: March 20, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-7136 Filed 3-23-12; 8:45 am]
BILLING CODE 4160-01-P


