81 FR 19066 - Administrative Actions for Noncompliance; Lesser Administrative Actions

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 64 (April 4, 2016)

Page Range		19066-19069
FR Document		2016-07524

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.

Federal Register, Volume 81 Issue 64 (Monday, April 4, 2016)

[Federal Register Volume 81, Number 64 (Monday, April 4, 2016)]
[Proposed Rules]
[Pages 19066-19069]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2016-07524]

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

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.

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

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).
---------------------------------------------------------------------------

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

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

19068 Federal Register / Vol. 81, No. 64 / Monday, April 4, 2016 / Proposed Rules

its noncompliance. We believe revising A significant adverse comment is one 12866, Executive Order 13563, the
§ 56.120(b) will improve the clarity and that explains why the rule would be Regulatory Flexibility Act (5 U.S.C.
accuracy of the regulations. We are also inappropriate (including challenges to 601–612), and the Unfunded Mandates
proposing to redesignate § 56.120(b)(4) the rule’s underlying premise or Reform Act of 1995 (Pub. L. 104–4).
as § 56.120(c), and § 56.120(c) as approach), or would be ineffective or Executive Orders 12866 and 13563
§ 56.120(d). unacceptable without a change. In direct us to assess all costs and benefits
FDA may notify relevant State and determining whether an adverse of available regulatory alternatives and,
Federal regulatory Agencies when comment is significant and warrants when regulation is necessary, to select
warranted to assure that organizations withdrawing a direct final rule, we regulatory approaches that maximize
with a need to know about the IRB’s consider whether the comment raises an net benefits (including potential
apparent noncompliance are issue serious enough to warrant a economic, environmental, public health
appropriately informed. The revision substantive response in a notice-and- and safety, and other advantages;
would eliminate confusion by stating comment process in accordance with distributive impacts; and equity). We
clearly that FDA is authorized to notify section 553 of the APA (5 U.S.C. 553). believe that this proposed rule is not a
others about the IRB’s noncompliance. Comments that are frivolous, significant regulatory action as defined
We believe these changes will ensure insubstantial, or outside the scope of the by Executive Order 12866.
clarity and improve the accuracy of the rule will not be considered adverse. A
regulations. comment recommending a rule change The Regulatory Flexibility Act
in addition to the rule would not be requires us to analyze regulatory options
II. Why is FDA publishing this that would minimize any significant
proposed rule? considered a significant adverse
comment, unless the comment states impact of a rule on small entities.
This proposed rule is a companion to why the rule would be ineffective Because this proposed rule would not
a direct final rule affirming FDA’s add any additional regulatory burdens,
without the additional change. In
longstanding interpretation of we propose to certify that this proposed
addition, if a significant adverse
§ 56.120(b), i.e., that FDA may impose rule will not have a significant
comment applies to part of a rule and
these restrictions on a noncompliant economic impact on a substantial
that part can be severed from the
IRB until the IRB takes appropriate number of small entities.
remainder of the rule, we may adopt as
corrective action. The direct final rule is
final those parts of the rule that are not Section 202(a) of the Unfunded
published in the final rules section of
the subject of a significant adverse Mandates Reform Act of 1995 requires
this issue of the Federal Register. The
comment. us to prepare a written statement, which
direct final rule and this companion
You can find additional information includes an assessment of anticipated
proposed rule are substantively
about FDA’s direct final rulemaking costs and benefits, before proposing
identical. This companion proposed
procedures in the guidance document ‘‘any rule that includes any Federal
rule will serve the purpose of issuing a
entitled ‘‘Guidance for FDA and mandate that may result in the
proposed rule under usual notice-and-
Industry: Direct Final Rule expenditure by State, local, and tribal
comment procedures in the event we
Procedures,’’ 1 announced in the governments, in the aggregate, or by the
withdraw the direct final rule because
Federal Register of November 21, 1997 private sector, of $100,000,000 or more
we receive significant adverse comment.
We are publishing the direct final rule (62 FR 62466). (adjusted annually for inflation) in any
because we believe it is III. Legal Authority one year.’’ The current threshold after
noncontroversial, and we do not This proposed rule, if finalized, adjustment for inflation is $144 million,
anticipate any significant adverse would amend § 56.120(b). FDA’s using the most current (2014) Implicit
comments. If we do not receive any authority to modify § 56.120(b) arises Price Deflator for the Gross Domestic
significant adverse comments in from the same authority under which Product. This proposed rule would not
response to the direct final rule, we will result in an expenditure in any year that
FDA initially issued this regulation, the
not take any further action on this meets or exceeds this amount.
IRB regulations, and general
proposed rule. Instead, within 30 days The purpose of this proposed rule is
administrative provisions of the Federal
after the comment period ends, we to affirm FDA’s longstanding
Food, Drug, and Cosmetic Act (21 U.S.C.
intend to publish a notice that confirms interpretation of § 56.120(b), that FDA
321, 343, 346, 346a, 348, 350a, 350b,
the effective date of the direct final rule.
351, 352, 353, 355, 360, 360c–360f, may impose these restrictions on a
If FDA receives any significant
360h, 360i, 360j, 360hh–360ss, 371, noncompliant IRB until the IRB takes
adverse comment regarding the direct
final rule, we will publish a notice of 379e, 381; 42 U.S.C. 216, 241, 262). appropriate corrective action. The
significant adverse comment and amendment will improve the clarity and
IV. Analysis of Environmental Impact
withdraw the direct final rule within 30 accuracy of the regulations. Because this
We have determined under 21 CFR proposed rule is a clarification and
days after the comment period ends. We 25.30(h) and 25.34(a) that this action is
will then proceed to final rulemaking would impose no additional regulatory
of a type that does not individually or burdens, this regulation is not
using our usual notice-and-comment cumulatively have a significant effect on
rulemaking procedures under the anticipated to result in any compliance
the human environment. Therefore, costs and the economic impact is
Administrative Procedure Act (APA). neither an environmental assessment
The comment period for this companion expected to be minimal.
mstockstill on DSK4VPTVN1PROD with PROPOSALS

nor an environmental impact statement
proposed rule runs concurrently with is required. VI. Paperwork Reduction Act of 1995
the direct final rule’s comment period.
We will consider any comments that we V. Economic Analysis of Impacts FDA tentatively concludes that this
receive in response to this companion We have examined the impacts of the proposed rule contains no collection of
proposed rule to be comments also proposed rule under Executive Order information. Therefore, clearance by the
regarding the direct final rule and vice Office of Management and Budget under
versa. We do not intend to provide 1 http://www.fda.gov/regulatoryinformation/ the Paperwork Reduction Act of 1995 is
additional opportunity for comment. guidances/ucm125166.htm. not required.

VerDate Sep<11>2014 18:23 Apr 01, 2016 Jkt 238001 PO 00000 Frm 00009 Fmt 4702 Sfmt 4702 E:\FR\FM\04APP1.SGM 04APP1

Document Created: 2016-04-02 03:54:29
Document Modified: 2016-04-02 03:54:29

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Proposed Rules
Action		Proposed rule.
Dates		Submit electronic or written comments on this proposed rule or its companion direct final rule by June 20, 2016.
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.
FR Citation		81 FR 19066
CFR Associated		Human Research Subjects; Reporting and Recordkeeping Requirements and Safety

81 FR 19066 - Administrative Actions for Noncompliance; Lesser Administrative Actions

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 81, Issue 64 (April 4, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration