[Federal Register Volume 83, Number 18 (Friday, January 26, 2018)]
[Rules and Regulations]
[Pages 3586-3589]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-01468]


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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

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
amending the general biologics regulations relating to time of 
inspection requirements and also removing duties of inspector 
requirements. FDA is taking this action to remove outdated requirements 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. This action is part of 
FDA's implementation of Executive Orders (E.O.s) 13771 and 13777. Under 
these E.O.s, 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. 
The Agency is issuing these amendments directly as a final rule because 
we believe they are noncontroversial and FDA anticipates no significant 
adverse comments.

DATES: This rule is effective June 11, 2018. Submit either electronic 
or written comments on the direct final rule or its companion proposed 
rule by April 11, 2018. If FDA receives no significant adverse comments 
within the specified comment period, the Agency intends to publish a 
document confirming the effective date of the final rule in the Federal 
Register within 30 days after the comment period on this direct final 
rule ends. If timely significant adverse comments are received, the 
Agency will publish a document in the Federal Register withdrawing this 
direct final rule within 30 days after the comment period on this 
direct final rule ends.

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

[[Page 3587]]

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 Direct Final Rule

    FDA is issuing this direct final rule to amend the general 
biologics regulations relating to time of inspection requirements and 
to remove duties of inspector requirements. FDA is taking 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 Direct Final Rule

    This direct final rule revises the time of inspection requirements 
contained in Sec.  600.21 (21 CFR 600.21) and also removes the duties 
of inspector requirements contained in Sec.  600.22 (21 CFR 600.22). 
These changes to the biological product regulations 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 does 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)).

C. Legal Authority

    FDA is taking 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 direct final rule does 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. Direct Final Rulemaking

    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), FDA described its procedures on 
when and how the Agency will employ direct final rulemaking. The 
guidance may be accessed at: https://www.fda.gov/RegulatoryInformation/Guidances/ucm125166.htm. We have determined that this rule is 
appropriate for direct final rulemaking because we believe that it 
includes only noncontroversial amendments and we anticipate no 
significant adverse comments. Consistent with our procedures on direct 
final rulemaking, FDA is also publishing elsewhere in this issue of the 
Federal Register a companion proposed rule proposing to amend the 
general biological products regulations by removing certain time of 
inspection requirements and the duties of inspector requirements. The 
companion proposed rule provides a procedural framework within which 
the rule may be finalized in the event that the direct final rule is 
withdrawn because of any significant adverse comments. The comment 
period for the direct final rule runs concurrently with the companion 
proposed rule. Any comments received in response to the companion 
proposed rule will be considered as comments regarding the direct final 
rule.
    We are providing a comment period on the direct final rule of 75 
days after the date of publication in the Federal Register. If we 
receive any significant adverse comments, we intend to withdraw this 
direct final rule before its effective date by publication of a notice 
in the Federal Register. 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 this 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 are received during the comment 
period, FDA will publish, before the effective date of this direct 
final rule, a notice of significant adverse comment and withdraw the 
direct final rule. If we withdraw the direct final rule, any comments 
received will be applied to the proposed rule and will be considered in 
developing a final rule using the usual notice-and-comment procedure.
    If FDA receives no significant adverse comments during the 
specified

[[Page 3588]]

comment period, FDA intends to publish a document confirming the 
effective date within 30 days after the comment period ends.

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 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 authority provided in the FD&C Act 
and the PHS Act, FDA is revising 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 removing 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 removing Sec.  
600.22(a) through (h).
    The removal of these regulations, however, does 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 does not change the established process for risk-based 
inspection planning and work planning.

IV. Highlights of the Direct Final Rule

    FDA is revising 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 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. FDA is issuing these revisions directly as a 
final rule because the Agency believes they include only 
noncontroversial amendments and FDA anticipates no significant adverse 
comments.

V. Legal Authority

    FDA is issuing this 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 direct final rule under 
Executive Order

[[Page 3589]]

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 direct 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 direct final rule does not impose any additional 
regulatory burdens, we certify that this direct 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 $148 
million, using the most current (2016) Implicit Price Deflator for the 
Gross Domestic Product. This direct final rule would not result in an 
expenditure in any year that meets or exceeds this amount.
    This rule is being issued to amend the general biologics 
regulations by removing time of inspection requirements and the duties 
of inspector requirements. This action is being taken to remove 
outdated requirements, accommodate new approaches, and provide 
flexibility without diminishing public health protections. Because this 
rulemaking would remove regulations to be consistent with updated 
practice and does not impose any additional regulatory burdens, this 
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 direct final rule in accordance with the 
principles set forth in Executive Order 13132. We have 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, 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

    This direct final 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 Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, 21 CFR part 600 is 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. 2018-01468 Filed 1-25-18; 8:45 am]
 BILLING CODE 4164-01-P