[Federal Register Volume 81, Number 64 (Monday, April 4, 2016)]
[Rules and Regulations]
[Pages 19033-19036]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-07523]


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

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: Direct final rule.

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

SUMMARY: The Food and Drug Administration (FDA) is amending 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: This rule is effective August 17, 2016. Submit electronic or 
written comments on this direct final rule or its companion proposed 
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 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): 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

[[Page 19034]]

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 amending 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. We are publishing this direct final rule because it is 
intended to clarify an existing regulation, and we do not anticipate 
any significant adverse comment regarding this amendment to Sec.  
56.120(b). Specifically, this direct final rule would 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 renumbers 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 drug 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 direct final rule amends Sec.  56.120(b) to read, 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 
its noncompliance. We believe revising Sec.  56.120(b) as described in 
this document will improve the clarity and accuracy of the regulations. 
We are also renumbering Sec.  56.120(b)(4) as Sec.  56.120(c), and 
Sec.  56.120(c) as Sec.  56.120(d). We are inserting ``FDA may'' into 
newly designated Sec.  56.120(c) so that it is a complete sentence.
    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. Procedures for Issuing a Direct Final Rule

    In the Federal Register of November 21, 1997 (62 FR 62466), FDA 
announced the availability of the guidance document entitled ``Guidance 
for FDA and Industry: Direct Final Rule Procedures'' \1\ that described 
when and how we will employ direct final rulemaking. We believe that 
this rule is

[[Page 19035]]

appropriate for direct final rulemaking because it is intended to 
clarify an existing regulation. We anticipate no significant adverse 
comment.
---------------------------------------------------------------------------

    \1\ http://www.fda.gov/regulatoryinformation/guidances/ucm125166.htm.
---------------------------------------------------------------------------

    Consistent with FDA's direct final rulemaking procedures, we are 
publishing a companion proposed rule elsewhere in this issue of the 
Federal Register. That proposed rule is identical in substance to this 
direct final rule. The companion proposed rule will serve the purpose 
of issuing a proposed rule under usual notice-and-comment procedures in 
the event we withdraw this direct final rule because we receive 
significant adverse comment. The comment period for this direct final 
rule runs concurrently with the comment period of the companion 
proposed rule. We will consider any comments that we receive in 
response to the companion proposed rule to be comments also regarding 
this direct final rule and vice versa.
    If FDA receives any significant adverse comment, we will withdraw 
this direct final rule before its effective date by publishing a notice 
in the Federal Register within 30 days after the comment period ends. 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 
Administrative Procedure Act (APA) (5 U.S.C. 553). Comments that are 
frivolous, insubstantial, or outside the scope of the rule would 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.
    If we withdraw this direct final rule, FDA will consider all 
comments that we received regarding the companion proposed rule as we 
develop a final rule through the usual notice-and-comment procedures of 
the APA. If we receive no significant adverse comment during the 
specified comment period regarding this direct final rule, we intend to 
publish a confirmation notice in the Federal Register within 30 days 
after the comment period ends.

III. Legal Authority

    This 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 Impact

    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 
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 this rule does not add any additional regulatory 
burdens, we certify that this final 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 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 $144 
million, using the most current (2014) Implicit Price Deflator for the 
Gross Domestic Product. This final rule would not result in an 
expenditure in any year that meets or exceeds this amount.
    The purpose of this final rule is to affirm FDA's longstanding 
interpretation of Sec.  56.120(b), that FDA may impose these 
administrative actions on a noncompliant IRB until the IRB takes 
appropriate corrective action. The amendment will improve the clarity 
and accuracy of the regulations. Because this final 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

    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.

VII. Federalism

    We have 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.

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, 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:

[[Page 19036]]

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. 2016-07523 Filed 4-1-16; 8:45 am]
 BILLING CODE 4164-01-P