[Federal Register Volume 83, Number 18 (Friday, January 26, 2018)]
[Proposed Rules]
[Pages 3631-3635]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-01467]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 600

[Docket No. FDA-2017-N-7007]
RIN 0910-AH49


Removal of Certain Time of Inspection and Duties of Inspector 
Regulations for Biological Products; Companion to Direct Final Rule

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
proposing to amend the general biologics regulations relating to time 
of inspection requirements and also removing duties of inspector 
requirements. FDA is proposing this action to remove outdated 
requirements and accommodate new approaches,

[[Page 3632]]

such as a risk-based inspection frequency for drug establishments, 
thereby providing flexibility without diminishing public health 
protections. This action is part of FDA's implementation of Executive 
Orders (EOs) 13771 and 13777. Under these EOs, FDA is comprehensively 
reviewing existing regulations to identify opportunities for repeal, 
replacement, or modification that will result in meaningful burden 
reduction while allowing the Agency to achieve our public health 
mission and fulfill statutory obligations.

DATES: Submit either electronic or written comments on the proposed 
rule or its companion direct final rule by April 11, 2018. If FDA 
receives any timely significant adverse comments on the direct final 
rule with which this proposed rule is associated, the Agency will 
publish a document withdrawing the direct final rule within 30 days 
after the comment period ends. FDA will apply any significant adverse 
comments received on the direct final rule to the proposed rule in 
developing the final rule. FDA will then proceed to respond to comments 
under this proposed rule using the usual notice and comment procedures.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before April 11, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of April 11, 2018. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions.'')

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-N-7007 for ``Removal of Certain Time of Inspection and Duties 
of Inspector Regulations for Biological Products.'' Received comments, 
those filed in a timely manner (see ADDRESSES), will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Melissa Segal, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION: 

I. Executive Summary

A. Purpose of the Proposed Rule

    FDA is proposing to amend the general biologics regulations 
relating to time of inspection requirements and to remove duties of 
inspector requirements. FDA is proposing this action to remove outdated 
requirements and accommodate new approaches, such as a risk-based 
inspection frequency for drug establishments, thereby providing 
flexibility without diminishing public health protections.

B. Summary of the Major Provisions of the Proposed Rule

    This proposed rule would revise the time of inspection requirements 
contained in Sec.  600.21 (21 CFR 600.21) and also remove the duties of 
inspector requirements contained in Sec.  600.22 (21 CFR 600.22). These 
changes to the biological product regulations would eliminate outdated 
requirements and accommodate new approaches, such as a risk-based 
inspection frequency for drug establishments, thereby providing 
flexibility without diminishing public health protections. Revision and 
removal of these regulations would not change the biological product 
establishment inspection requirements and duties of an investigator 
requirements that apply under sections 704 and 510(h) of the Federal 
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 374 and 360(h)) and 
section 351(c) of the Public Health Service Act (PHS Act) (42 U.S.C. 
262(c)).

[[Page 3633]]

C. Legal Authority

    FDA is proposing this action under the biological product 
provisions of the PHS Act, and the drugs and general administrative 
provisions of the FD&C Act, including sections 704 and 510(h) of the 
FD&C Act and section 351(c) of the PHS Act.

D. Costs and Benefits

    Because this proposed rule would not impose any additional 
regulatory burdens, this regulation is not anticipated to result in any 
compliance costs and the economic impact is expected to be minimal.

II. Companion Document to Direct Final Rulemaking

    This proposed rule is a companion to the direct final rule 
published in the rules section of this issue of the Federal Register. 
This companion proposed rule provides the procedural framework to 
finalize the rule in the event that the direct final rule receives any 
significant adverse comment and is withdrawn. The comment period for 
this companion proposed rule runs concurrently with the comment period 
for the direct final rule. Any comments received in response to this 
companion proposed rule will also be considered as comments regarding 
the direct final rule. FDA is publishing the direct final rule because 
we believe the rule contains noncontroversial changes and there is 
little likelihood that there will be significant adverse comments 
opposing the rule.
    A significant adverse comment is defined as a comment that explains 
why the rule would be inappropriate, including challenges to the rule's 
underlying premise or approach, or would be ineffective or unacceptable 
without a change. In determining whether an adverse comment is 
significant and warrants terminating a direct final rulemaking, we will 
consider whether the comment raises an issue serious enough to warrant 
a substantive response in a notice-and-comment process. Comments that 
are frivolous, insubstantial, or outside the scope of the rule will not 
be considered significant or adverse under this procedure. A comment 
recommending a regulation change in addition to those in the direct 
final rule would not be considered a significant adverse comment unless 
the comment states why the rule would be ineffective without the 
additional change. In addition, if a significant adverse comment 
applies to a part of the direct final rule and that part can be severed 
from the remainder of the rule, we may adopt as final those provisions 
of the rule that are not the subject of the significant adverse 
comment.
    If any significant adverse comments to the direct final rule are 
received during the comment period, FDA will publish, within 30 days 
after the comment period ends, a notice of significant adverse comment 
and withdraw the direct final rule. If we withdraw the direct final 
rule, any comments received will be considered comments on the proposed 
rule and will be considered in developing a final rule using the usual 
notice-and-comment procedure.
    If no significant adverse comment is received in response to the 
direct final rule during the comment period, no further action will be 
taken related to this proposed rule. Instead, we will publish a 
document confirming the effective date within 30 days after the comment 
period ends. Additional information about direct final rulemaking 
procedures is set forth in the document entitled ``Guidance for FDA and 
Industry: Direct Final Rule Procedures,'' announced and provided in the 
Federal Register of November 21, 1997 (62 FR 62466). The guidance may 
be accessed at: https://www.fda.gov/RegulatoryInformation/Guidances/ucm125166.htm.

III. Background

    On February 24, 2017, President Donald Trump issued Executive Order 
13777, ``Enforcing the Regulatory Reform Agenda'' (82 FR 12285, March 
1, 2017). One of the provisions in the Executive Order requires 
Agencies to evaluate existing regulations and make recommendations to 
the Agency head regarding their repeal, replacement, or modification, 
consistent with applicable law. As one step in implementing the 
Executive Order, FDA published a notice in the Federal Register of 
September 8, 2017 (82 FR 42492) entitled ``Review of Existing Center 
for Biologics Evaluation and Research Regulatory and Information 
Collection Requirements.'' In that notice, FDA announced that it was 
conducting a review of existing regulations to determine, in part, 
whether they can be made more effective in light of current public 
health needs and to take advantage of, and support, advances in 
innovation that have occurred since those regulations took effect. As 
part of this initiative, FDA is updating outdated regulations as 
specified in this rule.
    FDA's general biological products regulations in part 600 (21 CFR 
part 600) are intended to help ensure the safety, purity, and potency 
of biological products administered to humans. The proposed revision 
and removal of certain general biological products regulations are 
designed to eliminate outdated requirements and accommodate new 
approaches, such as a risk-based inspection frequency for drug 
establishments and provide flexibility without diminishing public 
health protections.

A. Section 600.21

    The authority for FDA to conduct establishment inspections is 
included in both the FD&C Act and the PHS Act. Specifically, section 
704 of the FD&C Act and section 351(c) of the PHS Act authorize the 
Agency to inspect establishments that manufacture biological products. 
Before July 9, 2012--the date the Food and Drug Administration Safety 
and Innovation Act (FDASIA) (Pub. L. 112-144) was signed into law--
section 510(h) of the FD&C Act further provided, among other things, 
that drug and device establishments registered with FDA must be 
inspected at least once in the 2-year period beginning with the date of 
registration and at least once in every successive 2-year period 
thereafter. Section 510(h) of the FD&C Act applies to biological 
product establishments because all biological products are subject to 
regulation under the drug or device provisions of the FD&C Act (in 
addition to the biological product provisions of the PHS Act). Since 
1983, FDA's biological product regulation at Sec.  600.21 has also 
included a biennial inspection requirement (``[A]n inspection of each 
licensed establishment and its additional location(s) shall be made at 
least once every 2 years''); this was consistent with the pre-FDASIA 
biennial inspection requirement in section 510(h) of the FD&C Act.
    With the enactment of FDASIA, however, the biennial inspection 
requirement for drug establishments in section 510(h) of the FD&C Act 
was replaced with a requirement that FDA inspect drug establishments in 
accordance with a risk-based schedule established by FDA. Accordingly, 
for biological product establishments that are registered as drug 
establishments under section 510(h), the requirement in Sec.  600.21 
regarding the frequency of inspections is no longer consistent with the 
FD&C Act and is outdated (e.g., the risk-based inspection schedule for 
drug establishments may result in scheduling inspections at intervals 
of greater than 2 years for certain biological product establishments). 
For this reason, and to provide for greater flexibility in general with 
respect to determining the frequency of biological product 
establishment inspections under the

[[Page 3634]]

authority provided in the FD&C Act and the PHS Act, FDA proposes to 
revise Sec.  600.21 to remove the biennial inspection requirement for 
biological product establishments that are registered as drug 
establishments and for those that are registered as device 
establishments.
    In addition, Sec.  600.21 includes provisions concerning 
inspectional notice and the timing of pre-licensure reinspections of 
biological product establishments. These provisions are outdated and 
unnecessary. Inspectional notice is addressed in the Agency's practices 
for inspections in its Standard Operating Procedures and Policies and 
in the Investigations Operations Manual (IOM). With respect to the 
timing of a reinspection of a biological product establishment 
following the denial of a biologics license application, the general 
biologics licensing provision at 21 CFR 601.4, which was issued 
subsequent to Sec.  600.21, sets forth the administrative procedures 
following the denial of a license; accordingly, the specific provision 
in Sec.  600.21 regarding timing of a reinspection following denial of 
a license is unnecessary. Therefore, FDA is proposing to remove these 
provisions.

B. Section 600.22

    Current Sec.  600.22 requires specific duties of an FDA inspector. 
These existing codified requirements are unnecessary because they are 
duplicative of statutory requirements that apply to biological product 
inspections under section 704 of the FD&C Act. Specifically, the 
inspection requirements in section 704 of the FD&C Act encompass all of 
the requirements outlined in Sec.  600.22. Thus, we are proposing to 
remove Sec.  600.22(a) through (h).
    The removal of these regulations, however, would not change the 
establishment inspection requirements and duties of an investigator 
requirements specified in sections 704 and 510(h) of the FD&C Act, 
section 351(c) of the PHS Act, or the procedures described in the IOM. 
Additionally, it would not change the established process for risk-
based inspection planning and work planning.

IV. Highlights of the Proposed Rule

    FDA is proposing to amend the general biologics regulations by 
revising time of inspection requirements contained in Sec.  600.21 and 
also by removing the duties of inspector requirements contained in 
Sec.  600.22. These proposed changes are designed to remove the 
existing codified requirements that are outdated and to accommodate new 
approaches, such as a risk-based inspection frequency for biological 
product establishments, thereby providing flexibility without 
diminishing public health protections.

V. Legal Authority

    FDA is issuing this proposed rule under the biological products 
provisions of the PHS Act (42 U.S.C. 216, 262, 263, 263a, 264, and 
300aa-25) and the drugs and general administrative provisions of the 
FD&C Act (21 U.S.C. 321, 351, 352, 353, 355, 356c, 356e, 360, 360i, 
371, 374, and 379k-l). Under these provisions of the PHS Act and the 
FD&C Act, we have the authority to issue and enforce regulations 
designed to ensure that biological products are safe, pure, and potent, 
and prevent the introduction, transmission, and spread of communicable 
disease.

VI. Economic Analysis of Impacts

    We have examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, Executive Order 13771, 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). Executive Order 13771 
requires that the costs associated with significant new regulations 
``shall, to the extent permitted by law, be offset by the elimination 
of existing costs associated with at least two prior regulations.'' We 
believe that this proposed 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 proposed rule does not impose any additional 
regulatory burdens, we propose to certify that the proposed 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 proposing ``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 $148 million, using the most current (2016) Implicit 
Price Deflator for the Gross Domestic Product. This proposed rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.
    This proposed rule proposes amendments to the general biologics 
regulations by removing time of inspection requirements and the duties 
of inspector requirements. FDA is proposing this action to remove 
outdated requirements, accommodate new approaches, and provide 
flexibility without diminishing public health protections. Because this 
rulemaking proposes removal of regulations to be consistent with 
updated practice and does not impose any additional regulatory burdens, 
this proposed rulemaking is not anticipated to result in any compliance 
costs and the economic impact is expected to be minimal.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.31(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.

VIII. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
this proposed 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, 
we conclude 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.

IX. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collection of information. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 is not 
required.

List of Subjects in 21 CFR Part 600

    Biologics, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and the 
Public

[[Page 3635]]

Health Service Act, and under authority delegated to the Commissioner 
of Food and Drugs, it is proposed that 21 CFR part 600 be amended as 
follows:

PART 600--BIOLOGICAL PRODUCTS: GENERAL

0
1. The authority citation for part 600 continues to read as follows:

    Authority:  21 U.S.C. 321, 351, 352, 353, 355, 356c, 356e, 360, 
360i, 371, 374, 379k-l; 42 U.S.C. 216, 262, 263, 263a, 264, 300aa-
25.


Sec.  600.21  [Amended]

0
2. Amend Sec.  600.21 by removing the last three sentences.


Sec.  600.22  [Removed and Reserved]

0
3. Remove and reserve Sec.  600.22.

    Dated: January 23, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-01467 Filed 1-25-18; 8:45 am]
 BILLING CODE 4164-01-P


