[Federal Register Volume 81, Number 64 (Monday, April 4, 2016)]
[Proposed Rules]
[Pages 19066-19069]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-07524]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 56

[Docket No. FDA-2015-N-5052]


Administrative Actions for Noncompliance; Lesser Administrative 
Actions

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the regulation describing lesser administrative actions that may be 
imposed on an Institutional Review Board (IRB) that has failed to 
comply with FDA's IRB regulations. We are clarifying that FDA may 
require the IRB to withhold approval of new FDA-regulated studies, stop 
the enrollment of new subjects in ongoing studies, and terminate 
ongoing studies, or any combination of these actions, until the 
noncompliance with FDA's IRB regulations is corrected. We are taking 
this action to ensure clarity and improve the accuracy of the 
regulations.

DATES: Submit electronic or written comments on this proposed rule or 
its companion direct final rule by June 20, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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

[[Page 19067]]

manner detailed (see ``Written/Paper Submissions'' and 
``Instructions'').

Written/Paper Submissions

    Submit written/paper comments as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2015-N-5052 for ``Subpart E--Administrative Actions for 
Noncompliance; Lesser Administrative Actions.'' Received comments will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Sheila Brown, Office of Good Clinical 
Practice, Office of Special Medical Programs, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5129, Silver 
Spring, MD 20993-0002, 301-796-6563.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is proposing to amend the text of Sec.  56.120(b) (21 CFR 
56.120(b)), which describes lesser administrative actions that the 
Agency may impose on an IRB until the IRB takes appropriate action to 
correct the IRB's noncompliance. FDA is proposing this revision to 
clarify the language and improve the accuracy of the regulations. 
Specifically, this proposed rule would propose to amend Sec.  56.120(b) 
by clarifying that FDA has authority to require the IRB to withhold 
approval of new FDA-regulated studies conducted at the institution or 
reviewed by the IRB, direct that no new subjects be added to ongoing 
studies, and terminate ongoing studies provided that doing so would not 
endanger study subjects.
    This amendment also proposes to renumber current paragraphs (b)(4) 
and (c) as paragraphs (c) and (d), respectively, and inserts ``FDA 
may'' into newly designated paragraph (c) so that it is a complete 
sentence.
    FDA first proposed requirements for the composition and operations 
of institutional review committees in the ``Proposed Investigational 
Device Exemptions,'' published in the Federal Register of August 20, 
1976 (41 FR 35282; ``Proposed IDE Rule''). In that document, FDA 
proposed disqualification procedures for institutional review 
committees and requested comments on the proposed procedures and other 
possible administrative actions that FDA might take against a committee 
that is not in compliance with the regulations (41 FR 35282 at 35293). 
FDA also stated its intention to publish uniform, Agency-wide 
regulations governing clinical investigations at a later date, 
including requirements governing institutional review committees (41 FR 
35282 at 35283).
    Subsequently, FDA published ``Standards for Institutional Review 
Boards for Clinical Investigations'' on August 8, 1978 (43 FR 35186; 
``Proposed IRB Standards''). Comments on implementing institutional 
review requirements received in response to the Proposed IDE Rule were 
reviewed and utilized in preparing the Proposed IRB Standards (43 FR 
35186 at 35187). In the Proposed IRB Standards, FDA proposed that 
disqualification would be used only if the Commissioner of Food and 
Drugs finds that: (1) The IRB failed to comply with one or more of the 
standards for IRBs in part 56 or other supplemental requirements in the 
investigational new drugs or investigational device exemptions (IDE) 
regulations; (2) the noncompliance adversely affects the validity of 
the data or the rights or safety of the human subjects; and (3) other 
lesser regulatory actions (e.g., warnings or rejection of data from 
individual clinical investigations) have not been or probably will not 
be adequate in achieving compliance (43 FR 35186 at 35195).
    FDA received numerous comments to the Proposed IRB Standards, and 
addressed those comments in the Federal Register of January 27, 1981 
(46 FR 8958), ``Protection of Human Subjects: Standards for 
Institutional Review Boards for Clinical Investigations, Final Rule.'' 
Specifically, several comments suggested that any lesser regulatory 
actions should be listed (46 FR 8958 at 8973). FDA accepted these 
comments and revised Sec.  56.120(b) to set forth the lesser 
administrative actions that the Agency may take if FDA finds 
deficiencies in the operation of an IRB and to describe the 
circumstances in which these lesser administrative actions may be used 
by the Agency. FDA's longstanding interpretation of Sec.  56.120(b) is 
that FDA may impose these restrictions on a noncompliant IRB until the 
IRB takes appropriate corrective action. The text of the regulation, 
however, suggests that it is the Agency that would withhold approval of 
studies that have been reviewed by a noncompliant IRB, rather than 
authorizing FDA to direct the IRB to stop approving new studies until 
the IRB comes back into compliance.
    This proposed rule would amend Sec.  56.120(b) to read that, in 
addition, until the IRB or the parent institution takes appropriate 
corrective action, the Agency may require the IRB to withhold approval 
of new studies, direct that no new subjects be added to ongoing 
studies, or terminate ongoing studies. This will ensure that those 
activities are suspended until the IRB takes appropriate corrective 
action to address

[[Page 19068]]

its noncompliance. We believe revising Sec.  56.120(b) will improve the 
clarity and accuracy of the regulations. We are also proposing to 
redesignate Sec.  56.120(b)(4) as Sec.  56.120(c), and Sec.  56.120(c) 
as Sec.  56.120(d).
    FDA may notify relevant State and Federal regulatory Agencies when 
warranted to assure that organizations with a need to know about the 
IRB's apparent noncompliance are appropriately informed. The revision 
would eliminate confusion by stating clearly that FDA is authorized to 
notify others about the IRB's noncompliance. We believe these changes 
will ensure clarity and improve the accuracy of the regulations.

II. Why is FDA publishing this proposed rule?

    This proposed rule is a companion to a direct final rule affirming 
FDA's longstanding interpretation of Sec.  56.120(b), i.e., that FDA 
may impose these restrictions on a noncompliant IRB until the IRB takes 
appropriate corrective action. The direct final rule is published in 
the final rules section of this issue of the Federal Register. The 
direct final rule and this companion proposed rule are substantively 
identical. This companion proposed rule will serve the purpose of 
issuing a proposed rule under usual notice-and-comment procedures in 
the event we withdraw the direct final rule because we receive 
significant adverse comment. We are publishing the direct final rule 
because we believe it is noncontroversial, and we do not anticipate any 
significant adverse comments. If we do not receive any significant 
adverse comments in response to the direct final rule, we will not take 
any further action on this proposed rule. Instead, within 30 days after 
the comment period ends, we intend to publish a notice that confirms 
the effective date of the direct final rule.
    If FDA receives any significant adverse comment regarding the 
direct final rule, we will publish a notice of significant adverse 
comment and withdraw the direct final rule within 30 days after the 
comment period ends. We will then proceed to final rulemaking using our 
usual notice-and-comment rulemaking procedures under the Administrative 
Procedure Act (APA). The comment period for this companion proposed 
rule runs concurrently with the direct final rule's comment period. We 
will consider any comments that we receive in response to this 
companion proposed rule to be comments also regarding the direct final 
rule and vice versa. We do not intend to provide additional opportunity 
for comment.
    A significant adverse comment is one 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 withdrawing a direct final rule, we consider whether the 
comment raises an issue serious enough to warrant a substantive 
response in a notice-and-comment process in accordance with section 553 
of the APA (5 U.S.C. 553). Comments that are frivolous, insubstantial, 
or outside the scope of the rule will not be considered adverse. A 
comment recommending a rule change in addition to the 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 part of a rule 
and that part can be severed from the remainder of the rule, we may 
adopt as final those parts of the rule that are not the subject of a 
significant adverse comment.
    You can find additional information about FDA's direct final 
rulemaking procedures in the guidance document entitled ``Guidance for 
FDA and Industry: Direct Final Rule Procedures,'' \1\ announced in the 
Federal Register of November 21, 1997 (62 FR 62466).
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    \1\ http://www.fda.gov/regulatoryinformation/guidances/ucm125166.htm.
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III. Legal Authority

    This proposed rule, if finalized, would amend Sec.  56.120(b). 
FDA's authority to modify Sec.  56.120(b) arises from the same 
authority under which FDA initially issued this regulation, the IRB 
regulations, and general administrative provisions of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 321, 343, 346, 346a, 348, 350a, 350b, 
351, 352, 353, 355, 360, 360c-360f, 360h, 360i, 360j, 360hh-360ss, 371, 
379e, 381; 42 U.S.C. 216, 241, 262).

IV. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) and 25.34(a) 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.

V. Economic Analysis of Impacts

    We have examined the impacts of the proposed 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 
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 this proposed rule would not add any additional 
regulatory burdens, we propose to certify that this proposed rule will 
not have a significant economic impact on a substantial number of small 
entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 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 $144 million, using the most current (2014) 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.
    The purpose of this proposed rule is to affirm FDA's longstanding 
interpretation of Sec.  56.120(b), that FDA may impose these 
restrictions on a noncompliant IRB until the IRB takes appropriate 
corrective action. The amendment will improve the clarity and accuracy 
of the regulations. Because this proposed rule is a clarification and 
would impose no additional regulatory burdens, this regulation is not 
anticipated to result in any compliance costs and the economic impact 
is expected to be minimal.

VI. 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.

[[Page 19069]]

VII. Federalism

    We have analyzed this proposed 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.

List of Subjects in 21 CFR Part 56

    Human research subjects, Reporting and recordkeeping requirements, 
Safety.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 56 is amended as follows:

PART 56--INSTITUTIONAL REVIEW BOARDS

0
1. The authority citation for 21 CFR part 56 is revised to read as 
follows:

    Authority: 21 U.S.C. 321, 343, 346, 346a, 348, 350a, 350b, 351, 
352, 353, 355, 360, 360c-360f, 360h, 360i, 360j, 360hh-360ss, 371, 
379e, 381; 42 U.S.C. 216, 241, 262.

0
2. In Sec.  56.120, redesignate paragraphs (b)(4) and (c) as paragraphs 
(c) and (d), respectively, and revise paragraph (b) and newly 
designated paragraph (c) to read as follows:


Sec.  56.120  Lesser administrative actions.

* * * * *
    (b) On the basis of the IRB's or the institution's response, FDA 
may schedule a reinspection to confirm the adequacy of corrective 
actions. In addition, until the IRB or the parent institution takes 
appropriate corrective action, the Agency may require the IRB to:
    (1) Withhold approval of new studies subject to the requirements of 
this part that are conducted at the institution or reviewed by the IRB;
    (2) Direct that no new subjects be added to ongoing studies subject 
to this part; or
    (3) Terminate ongoing studies subject to this part when doing so 
would not endanger the subjects.
    (c) When the apparent noncompliance creates a significant threat to 
the rights and welfare of human subjects, FDA may notify relevant State 
and Federal regulatory agencies and other parties with a direct 
interest in the Agency's action of the deficiencies in the operation of 
the IRB.
* * * * *

    Dated: March 29, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-07524 Filed 4-1-16; 8:45 am]
 BILLING CODE 4164-01-P