[Federal Register Volume 87, Number 187 (Wednesday, September 28, 2022)]
[Proposed Rules]
[Pages 58733-58752]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-21088]


 ========================================================================
 Proposed Rules
                                                 Federal Register
 ________________________________________________________________________
 
 This section of the FEDERAL REGISTER contains notices to the public of 
 the proposed issuance of rules and regulations. The purpose of these 
 notices is to give interested persons an opportunity to participate in 
 the rule making prior to the adoption of the final rules.
 
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 

  Federal Register / Vol. 87, No. 187 / Wednesday, September 28, 2022 / 
Proposed Rules  

[[Page 58733]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 50, 56, and 812

[Docket No. FDA-2021-N-0286]
RIN 0910-AI07


Protection of Human Subjects and Institutional Review Boards

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is proposing 
to amend its regulations to modernize, simplify, and enhance the 
current system for oversight of FDA-regulated human subject research. 
This proposed rule, if finalized, would harmonize certain sections of 
FDA's regulations on human subject protection and institutional review 
boards (IRBs), to the extent practicable and consistent with other 
statutory provisions, with the revised Federal Policy for the 
Protection of Human Subjects (the revised Common Rule), in accordance 
with the 21st Century Cures Act (Cures Act). We believe the proposed 
changes, if finalized, will reduce regulatory burden on IRBs, sponsors, 
and investigators. In addition, we propose related changes to the 
investigational device exemption (IDE) regulations to clarify and 
update the requirements for the submission of progress reports.

DATES: Either electronic or written comments on the proposed rule must 
be submitted by November 28, 2022. Submit written comments (including 
recommendations) on the collection of information under the Paperwork 
Reduction Act of 1995 by November 28, 2022.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of November 28, 2022. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are received 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-2021-N-0286 for ``Protection of Human Subjects and Institutional 
Review Boards.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     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.govinfo.gov/content/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, 240-402-7500.
    Submit comments on information collection issues under the 
Paperwork Reduction Act of 1995 to the Office of Management and Budget 
(OMB) at https://www.reginfo.gov/public/do/PRAMain. Find this 
particular information collection by selecting ``Currently under 
Review--Open for Public Comments'' or by using the search function. The 
title of this proposed collection is ``Protection of

[[Page 58734]]

Human Subjects and Institutional Review Boards--21 CFR parts 50 and 56 
(OMB Control Number 0910-0130)''.

FOR FURTHER INFORMATION CONTACT: With regard to the proposed rule: 
Sheila Brown, Office of Clinical Policy, Food and Drug Administration, 
10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-6523, 
[email protected].
    With regard to the information collection: Domini Bean, Office of 
Operations, Food and Drug Administration, Three White Flint North 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
[email protected].

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of the Proposed Rule
    B. Summary of the Major Provisions of the Proposed Rule
    C. Legal Authority
    D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
    A. Human Subject Protection Requirements Under the Revised 
Common Rule
    B. FDA's Current Regulatory Framework
    C. The Cures Act
    D. Need for the Regulation
IV. Legal Authority
V. Description of the Proposed Rule
    A. 21 CFR Part 50--Protection of Human Subjects
    B. 21 CFR Part 56--Institutional Review Boards
    C. 21 CFR Part 812--Investigational Device Exemptions
VI. Proposed Effective Date
VII. Preliminary Economic Analysis of Impacts
    A. Introduction
    B. Summary of Costs and Benefits
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
    A. Protection of Human Subjects and Institutional Review 
Boards--Parts 50 and 56
    B. Investigational Device Exemptions--Part 812
X. Consultation and Coordination With Indian Tribal Governments
XI. Federalism
XII. Reference

I. Executive Summary

A. Purpose of the Proposed Rule

    The purpose of this proposed rule is to modernize, simplify, and 
enhance the current system for oversight of FDA-regulated human subject 
research. We propose to harmonize certain sections of FDA's regulations 
on human subject protection (part 50 (21 CFR part 50)) and IRBs (part 
56 (21 CFR part 56)), to the extent practicable and consistent with 
other statutory provisions, with the revised Common Rule,\1\ in 
accordance with section 3023 of the Cures Act (Pub. L. 114-255, enacted 
December 13, 2016).\2\ The rule also proposes to revise FDA's 
regulations on IDEs (part 812 (21 CFR part 812)) to clarify and update 
the requirements for submission of progress reports for clinical 
investigations of devices. We are also proposing minor technical and 
editorial changes to the regulations for clarity. FDA believes that 
these proposed changes, if finalized, would help ensure clarity and 
enhance both human subject protection and the IRB review process. In 
addition, harmonizing with the revised Common Rule would reduce 
regulatory burden for IRBs, sponsors, and investigators.
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    \1\ For the purposes of this proposed rule, the phrase ``revised 
Common Rule'' refers to the final rule (82 FR 7149, January 19, 
2017), modified by the interim final rule that delayed the effective 
date and general compliance date (83 FR 2885, January 22, 2018) and 
the final rule that delayed the general compliance date, while 
allowing use of three burden-reducing provisions for certain 
research during the delay period (83 FR 28497, June 19, 2018).
    \2\ The term ``harmonize,'' as used in this proposed rule means, 
``harmonize to the extent practicable and consistent with other 
statutory provisions,'' consistent with section 3023 of the Cures 
Act.
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B. Summary of the Major Provisions of the Proposed Rule

    This proposed rule, if finalized, would amend parts 50 and 56 of 
FDA's regulations. Among other things, we are proposing to: (1) revise 
the content, organization, and presentation of information included in 
the informed consent form and process to facilitate a prospective 
subject's decision about whether to participate in the research; (2) 
add new basic and additional elements of informed consent; (3) add a 
provision that would allow IRBs to eliminate continuing review of 
research in certain circumstances; (4) revise the IRB recordkeeping 
requirements for certain determinations related to the need for 
continuing review; and (5) add or modify some definitions. We are also 
proposing to revise one section of part 812 regarding progress reports 
submitted by investigators and sponsors to a reviewing IRB for 
consistency with other revisions we are proposing to the continuing 
review process in part 56.

C. Legal Authority

    The provisions under which FDA is proposing to issue this rule 
include sections 403, 406, 409, 412, 413, 503, 505, 510, 513-515, 520, 
531-539, 541-542, 701, and 721 of the Federal Food, Drug, and Cosmetic 
Act (FD&C Act) (21 U.S.C. 343, 346, 348, 350a, 350b, 353, 355, 360, 
360c-360e, 360j, 360hh-360pp, 360rr-360ss, 371, and 379e) and section 
351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262).

D. Costs and Benefits

    The primary quantifiable benefit of the proposed rule is a 
decreased time burden to IRBs, investigators, and sponsors of clinical 
trials from increased harmonization with the revised Common Rule. 
Quantifiable costs include the development of informed consent 
documents and additional recordkeeping burdens. The estimated 
annualized cost savings of the proposed rule range from approximately 
$22 to $103 million in 2018 dollars, with a central estimate of 
approximately $43 million, discounted at 7 percent over 10 years. At 3 
percent, estimates of annualized cost savings range from approximately 
$22 to $103 million, with a central estimate of approximately $43 
million. Estimated annualized costs of the proposed rule range from 
approximately $0.7 million to $2.3 million, with a central estimate of 
approximately $1.2 million, discounted at 7 percent. At 3 percent, 
estimates of annualized costs range from approximately $0.6 million to 
$2.0 million, with a central estimate of approximately $1.1 million. 
The impact of the proposed provisions is analyzed in the Preliminary 
Economic Analysis of Impacts for this proposed rule.

II. Table of Abbreviations/Commonly Used Acronyms in This Document

------------------------------------------------------------------------
     Abbreviation/acronym                    What it means
------------------------------------------------------------------------
Cures Act....................  21st Century Cures Act (Pub. L. 114-255).
FDA..........................  Food and Drug Administration.
IRB..........................  Institutional Review Board.
FD&C Act.....................  Federal Food, Drug, and Cosmetic Act.
FR...........................  Federal Register.
HHS..........................  Department of Health and Human Services.
IDE..........................  Investigational Device Exemption.

[[Page 58735]]

 
IND..........................  Investigational New Drug Application.
LAR..........................  Legally Authorized Representative.
NIH..........................  National Institutes of Health.
OHRP.........................  Office for Human Research Protections.
PRA..........................  Paperwork Reduction Act of 1995.
OMB..........................  Office of Management and Budget.
PHS Act......................  Public Health Service Act.
SACHRP.......................  Secretary's Advisory Committee on Human
                                Research Protections.
U.S.C........................  United States Code.
WGS..........................  Whole Genome Sequencing.
------------------------------------------------------------------------

III. Background

A. Human Subject Protection Requirements Under the Revised Common Rule

    The Federal Policy for the Protection of Human Subjects, codified 
by the Department of Health and Human Services (HHS) at 45 CFR part 46, 
subpart A, and generally referred to as the Common Rule, sets forth 
requirements for the protection of human subjects involved in research 
that is conducted or supported by HHS. The Common Rule was issued in 
1991 \3\ and has been adopted by other Federal Departments and 
Agencies. The purpose of the Common Rule is to promote uniformity, 
understanding, and compliance with human subject protections and to 
create a uniform body of regulations across the Federal Departments and 
Agencies.\4\ On January 19, 2017, HHS announced revisions to modernize, 
strengthen, and make the Common Rule more effective. The revised Common 
Rule is intended to better protect human subjects involved in research, 
while facilitating valuable research and reducing burden, delay, and 
ambiguity for the regulated community.\5\
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    \3\ 56 FR 28001, June 18, 1991.
    \4\ 80 FR 53933 at 53935, September 8, 2015.
    \5\ 82 FR 7149, January 19, 2017.
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B. FDA's Current Regulatory Framework

    FDA's regulations for the protection of human subjects at parts 50 
and 56 apply to clinical investigations, as defined at current 
Sec. Sec.  50.3(c) and 56.102(c), regardless of the source of funding. 
These regulations, which include requirements for informed consent and 
IRBs, are intended to protect the rights, safety, and welfare of 
subjects involved in clinical investigations involving FDA-regulated 
products.
    Prior to the most recent revision to the Common Rule, FDA's 
regulations regarding the protection of human subjects were largely 
consistent with the requirements in the Common Rule, with a few 
exceptions generally arising from differences in FDA's mission or 
statutory authority. FDA-regulated research that is HHS-conducted or 
HHS-supported is subject to both HHS's and FDA's regulations. Many IRBs 
review both types of research and must comply with both sets of 
regulations. FDA and the Office for Human Research Protections (OHRP) 
have been actively working together for many years to harmonize 
regulatory requirements and guidance.

 C. The Cures Act

    On December 13, 2016, the Cures Act was signed into law with its 
purpose of accelerating the discovery, development, and delivery of 
21st century cures.\6\ Section 3023 of the Cures Act directs the 
Secretary of HHS, to the extent practicable and consistent with other 
statutory provisions, to harmonize differences between the HHS Human 
Subject Regulations and FDA's Human Subject Regulations.\7\ Section 
3023 of the Cures Act further directs the Secretary of HHS to, as 
appropriate, make modifications to those regulations, in order to, 
among other things, reduce regulatory duplication and unnecessary 
delays. FDA is working with other HHS Agencies in carrying out this 
statutory mandate, and this proposed rule is being issued in accordance 
with this provision.
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    \6\ Public Law 114-255.
    \7\ Public Law 114-255, title III, section 3023, December 13, 
2016.
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D. Need for the Regulation

    As described above, FDA's regulations governing the protection of 
human subjects largely have been consistent with the requirements of 
the Common Rule, with a few exceptions generally due to differences in 
FDA's mission and statutory authority. The revised Common Rule includes 
provisions intended to strengthen the effectiveness of the human 
subject protection regulations, and FDA is proposing to harmonize with 
certain provisions in the revised Common Rule that are applicable to 
FDA-regulated clinical investigations. For example, proposed new basic 
and additional elements of informed consent, along with new 
requirements for the presentation of information in the consent form, 
would help facilitate a prospective subject's decision about whether to 
participate in the research and facilitate the enrollment process. In 
addition, FDA is proposing to harmonize with the revised Common Rule by 
adding provisions that reduce burden on IRBs and that are intended to 
allow IRBs to focus their resources on research that presents higher 
risk, thereby enhancing human subject protection. Harmonization will 
also reduce confusion and regulatory burden for the oversight of 
studies that are subject to both the revised Common Rule and FDA 
regulations.
    This proposed rule does not address all of the provisions contained 
in the revised Common Rule. The Agency has addressed some of these 
provisions in a previously issued proposed rule \8\ and is also 
considering how other provisions of the revised Common Rule that are 
potentially relevant to FDA-regulated research, such as provisions 
related to single IRB review for cooperative research, posting of 
informed consent forms, broad consent, limited IRB review, exempt 
research, and public health surveillance activities, could be applied 
to FDA-regulated research. FDA plans to take additional steps to 
harmonize FDA's regulations with the revised Common Rule, to the extent 
practicable and consistent with statutory provisions.
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    \8\ See FDA's notice of proposed rulemaking, ``Institutional 
Review Board Waiver or Alteration of Informed Consent for Minimal 
Risk Clinical Investigations,'' 83 FR 57378, November 15, 2018 
(https://www.govinfo.gov/content/pkg/FR-2018-11-15/pdf/2018-24822.pdf).
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IV. Legal Authority

    FDA is proposing to issue this rule under the Agency's authority to 
issue regulations regarding the investigational use of drugs under 
section 505(i) of the FD&C Act, the investigational use of devices 
under section 520(g) of the FD&C Act, and the investigational use of 
biological products under section 351(a) of the PHS Act. In addition, 
IRB review

[[Page 58736]]

helps assure the quality and integrity of data from clinical 
investigations relied upon in submissions to FDA regarding the safety, 
effectiveness, and/or marketing of FDA-regulated products, including 
submissions made pursuant to sections 403, 406, 409, 412, 413, 503, 
505, 510, 513-515, 520, 531-539, 541-542, and 721 of the FD&C Act and 
section 351 of the PHS Act. Requirements for informed consent and IRB 
review also help protect the rights and welfare of human subjects 
involved in those clinical investigations. Section 701(a) of the FD&C 
Act authorizes the Agency to issue regulations for the efficient 
enforcement of the FD&C Act.
    These statutory provisions authorize FDA to issue the proposed 
revisions to its regulations to enhance protection of human subjects 
and the IRB review process for FDA-regulated clinical investigations.

V. Description of the Proposed Rule

A. 21 CFR Part 50--Protection of Human Subjects

    We propose to revise part 50 by adding new requirements, including 
revised definitions intended to enhance human subject protections. 
These proposed revisions would require presentation of information in 
the informed consent document to be in an organized and understandable 
manner, and to include a concise and focused presentation of the key 
information most likely to assist a prospective subject in 
understanding the reasons why the subject might or might not want to 
participate in the research. The new proposed provisions also include a 
new basic element of informed consent and three new additional elements 
of informed consent. New proposed definitions include the definitions 
of private information, identifiable private information, and 
identifiable biospecimen. FDA is also proposing to make grammatical 
corrections or other editorial changes to provide clarity. Table 1 
summarizes the proposed changes to part 50 that would harmonize with 
the revised Common Rule.

                Table 1--Proposed Revisions to Part 50 To Harmonize With the Revised Common Rule
----------------------------------------------------------------------------------------------------------------
                                                                     Harmonizes with revised Common Rule section
           Section No.                     FDA proposes to:                       (45 CFR part 46)
----------------------------------------------------------------------------------------------------------------
50.3(l)..........................  Add a sentence to the            46.102(i).
                                    definition of legally
                                    authorized representative
                                    (LAR) to address situations in
                                    which there is no applicable
                                    State or local law governing
                                    who may act as a LAR.
50.3(t)..........................  Add a definition of ``written    46.102(m).
                                    or in writing'' that includes
                                    both physical and electronic
                                    formats.
50.3(u)..........................  Add a definition of ``private    46.102(e)(4).
                                    information''.
50.3(v)..........................  Add a definition of              46.102(e)(5).
                                    ``identifiable private
                                    information''.
50.3(w)..........................  Add a definition of              46.102(e)(6).
                                    ``identifiable biospecimen''.
50.20............................  Add provisions (d) and (e) for   46.116(a)(1)-(6).
                                    organizing and presenting
                                    information about the research
                                    to subjects; redesignate or
                                    make minor editorial changes
                                    to other portions of the
                                    paragraph.
50.25(a).........................  Add ``or legally authorized      46.116(b).
                                    representative'' to clarify to
                                    whom informed consent
                                    information must be provided.
50.25(a)(9)......................  Add a basic element of informed  46.116(b)(9).
                                    consent that would require a
                                    description of how information
                                    or biospecimens may be used
                                    for future research or
                                    distributed for future
                                    research.
50.25(b).........................  Add ``or the legally authorized  46.116(c).
                                    representative'' to the end of
                                    the sentence to clarify to
                                    whom informed consent
                                    information must be provided.
50.25(b)(2)......................  Add ``or legally authorized      46.116(c)(2).
                                    representative's'' to clarify
                                    that the investigator may
                                    terminate the research without
                                    the consent of the subject or
                                    the LAR.
50.25(b)(7)-(9)..................  Add three new additional         46.116(c)(7)-(9).
                                    elements of informed consent,
                                    including a statement as to
                                    how private information or
                                    biospecimens collected during
                                    the research may be used for
                                    commercial profit and whether
                                    the subject will or will not
                                    share in this commercial
                                    profit, whether clinically
                                    relevant results will be
                                    disclosed to study subjects,
                                    and for research involving
                                    biospecimens, whether the
                                    research involves whole genome
                                    sequencing.
50.25(d).........................  Add a reference to tribal law    46.116(i).
                                    of American Indian or Alaska
                                    Native tribes, to clarify that
                                    the reference to ``Federal,
                                    State, or local law'' is
                                    intended to include tribal
                                    laws; make minor editorial
                                    changes.
50.25(e).........................  Add a reference to tribal law    46.116(j).
                                    of American Indian or Alaska
                                    Native tribes, to clarify that
                                    the reference to ``Federal,
                                    State, or local law'' is
                                    intended to include tribal law.
50.27(a).........................  Add a parenthetical to provide   46.117(a).
                                    for consent forms in an
                                    electronic format and add
                                    ``informed consent'' before
                                    ``form''.
50.27(b)(1)......................  Add ``or the subject's legally   46.117(b)(1).
                                    authorized representative''
                                    (to clarify that the subject
                                    or LAR shall have the
                                    opportunity to read the
                                    informed consent form);
                                    reorder the sentences and make
                                    minor editorial changes.
50.27(b)(2)......................  Add a sentence to clarify that   46.117(b)(2)
                                    when using a short form
                                    written informed consent, the
                                    key information must be
                                    presented first to the subject
                                    before other information, if
                                    any, is provided, and add
                                    ``legally authorized
                                    representative'' in three
                                    places; reorder sentences and
                                    make minor editorial changes.
----------------------------------------------------------------------------------------------------------------

1. Definitions
    We propose to harmonize our definition of ``legally authorized 
representative'' at Sec.  50.3(l) with the definition in the revised 
Common Rule at 45 CFR 46.102(i), by adding a sentence to address 
situations in which there is no applicable State or local law that 
authorizes a LAR to provide consent on behalf of a prospective research 
subject. We propose that in these circumstances, an individual 
recognized by institutional policy as acceptable for providing consent 
in the nonresearch context may be considered a LAR for purposes of 
consenting to the subject's participation in the procedures involved in 
the research.
    In addition, we propose to add several new definitions that are 
used in the revised Common Rule. At Sec.  50.3(t), we propose to add 
the definition of ``written or in writing,'' which would harmonize with 
this definition in the revised Common Rule, at 45 CFR 46.102(m). The 
definition would include both paper and electronic

[[Page 58737]]

formats, the latter of which are increasingly used to fulfill many of 
the documentation requirements that appear throughout FDA's human 
subject protection regulations. This definition would help clarify that 
consent forms and related documentation (e.g., written summaries of 
what is said to subjects and LARs when a short form consent is used in 
accordance with Sec.  50.27(b)(2) and IRB findings required under Sec.  
50.24) may be in an electronic format.
    FDA is proposing to add three new definitions for the terms 
``private information,'' ``identifiable private information,'' and 
``identifiable biospecimen.'' The terms ``identifiable private 
information,'' and ``identifiable biospecimen'' and/or references to 
biospecimens are found in new proposed elements of informed consent at 
Sec.  50.25(a)(9), (b)(7), and (b)(9), and in the proposed provisions 
regarding IRB continuing review at Sec.  56.109(g)(1).\9\ FDA is 
proposing to add these new terms and definitions to help modernize our 
regulations to reflect the changing research landscape involving, for 
example, access to vast amounts of data from electronic health records 
and stored biospecimens, the ability to share data and biospecimens for 
research purposes, and the development of new technologies and analytic 
capabilities to advance science and the public health.
---------------------------------------------------------------------------

    \9\ We also note that FDA issued a proposed rule on November 15, 
2018, that proposed to permit an IRB to approve an informed consent 
procedure that waives or alters certain informed consent elements or 
that waives the requirement to obtain informed consent for certain 
minimal risk studies, when the IRB finds and documents four 
criteria. The proposed rule invited comment on a fifth criterion for 
IRB waiver or alteration of informed consent that was added to the 
revised Common Rule at 45 CFR 46.116(f)(3)(iii) and reads, ``if the 
research involves using identifiable private information or 
identifiable biospecimens, the research could not practicably be 
carried out without using such information or biospecimens in an 
identifiable format'' (see 83 FR 57378 at 57381). The comment period 
on the proposed rule is closed, and FDA is in the process of 
reviewing comments received on this fifth criterion. If the proposed 
rule is finalized in a form that includes the fifth criterion, the 
final provision would include references to ``identifiable private 
information'' and ``identifiable biospecimen''.
---------------------------------------------------------------------------

    We propose to add, at Sec.  50.3(u), a definition of ``private 
information'' that harmonizes with the definition of ``private 
information'' in the revised Common Rule, at 45 CFR 46.102(e)(4). 
Private information includes information about behavior that occurs in 
a context in which an individual can reasonably expect that no 
observation or recording is taking place, and information that has been 
provided for specific purposes by an individual and that the individual 
can reasonably expect will not be made public (e.g., a medical record).
    We propose to add, at Sec.  50.3(v), a definition of ``identifiable 
private information'' to harmonize with the revised Common Rule's 
definition of ``identifiable private information'' at 45 CFR 
46.102(e)(5). We propose to define ``identifiable private information'' 
as private information for which the identity of the subject is or may 
readily be ascertained by the sponsor or investigator or associated 
with the information. This definition differs from the text of the 
revised Common Rule provision by including information for which a 
subject's identity is or may be readily ascertained by the ``sponsor'' 
in addition to information that is or may be readily ascertained by the 
investigator. FDA would consider information for which a subject's 
identity is or may be readily ascertained by members of the research 
team conducting the investigation under the supervision of the 
investigator to be ``identifiable private information'' under this 
proposed definition.
    FDA's regulations define the terms ``sponsor'' and 
``investigator,'' and they are used throughout our regulations to 
describe the responsibilities that apply to certain parties involved in 
FDA-regulated research. OHRP has stated in guidance that it considers 
the term ``investigator'' to include ``anyone involved in conducting 
the research,'' \10\ which is broader than the definition of an 
``investigator'' under FDA's regulations (see, e.g., Sec.  50.3(d)). 
FDA believes that information for which a subject's identity is or may 
readily be ascertained by the sponsor of FDA-regulated research should 
be considered identifiable; and we believe adopting such an approach 
will help to harmonize the effects of the two sets of regulations.
---------------------------------------------------------------------------

    \10\ See OHRP's 2008 Guidance, ``Coded Private Information or 
Specimens Use in Research'', https://www.hhs.gov/ohrp/regulations-and-policy/guidance/research-involving-coded-private-information/index.html (accessed January 29, 2021).
---------------------------------------------------------------------------

    We propose to add, at Sec.  50.3(w), a definition of ``identifiable 
biospecimen,'' to harmonize with the revised Common Rule's definition 
of ``identifiable biospecimen'' at 45 CFR 46.102(e)(6). For the same 
reasons described above with respect to the definition of 
``identifiable private information'', we propose to define an 
identifiable biospecimen as a biospecimen for which the identity of the 
subject is or may readily be ascertained by the sponsor or investigator 
or associated with the biospecimen.
    The revised Common Rule also includes a provision at 45 CFR 
46.102(e)(7)(i) that requires the Federal Departments and Agencies 
implementing the revised Common Rule, upon consultation with 
appropriate experts, to reexamine the meaning of the terms 
``identifiable private information'' and ``identifiable biospecimen'' 
within 1 year and regularly thereafter (at least every 4 years). That 
provision further provides that if appropriate and permitted by law, 
these Federal Departments and Agencies may alter the interpretation of 
these terms, including through the use of guidance. FDA intends to 
participate in this effort with HHS and the other Federal Departments 
and Agencies.
2. General Requirements for Informed Consent
    We propose to amend the general requirements for informed consent 
under Sec.  50.20 to harmonize with the revised Common Rule at 45 CFR 
46.116(a)(1) through (6). These requirements address the content, 
organization, and presentation of information included in the consent 
form and process to facilitate a prospective subject's decision about 
whether to participate in the research. To this end, we propose to 
redesignate our existing requirements as Sec.  50.20(a), (b), (c), and 
(f) and add new paragraphs (d) and (e). New paragraph (d) would clarify 
that the prospective subject or the subject's legally authorized 
representative must be provided with the information that a reasonable 
person would want to have to make an informed decision about whether to 
participate and be given an opportunity to discuss that information.
    In new Sec.  50.20(e)(1) and (2), we propose to require that 
informed consent begin with a concise and focused presentation of the 
key information that is most likely to assist a prospective subject or 
LAR in understanding the reasons why the subject might or might not 
want to participate in the research, and that the information be 
organized and presented in a way that facilitates the subject's or 
LAR's comprehension.
3. Elements of Informed Consent
    We propose to add the phrase ``or legally authorized 
representative'' to Sec.  50.25(a) and (b), to harmonize with the 
revised Common Rule at 45 CFR 46.116(b) and (c), and to clarify to whom 
informed consent information must be provided.
    We propose to add a new basic element of informed consent at Sec.  
50.25(a)(9) to harmonize with the

[[Page 58738]]

revised Common Rule at 45 CFR 46.116(b)(9) and enhance human subject 
protections. While FDA is not proposing to use language verbatim from 
the revised Common Rule for this new basic element of informed consent 
at Sec.  50.25(a)(9), our proposal similarly requires the provision of 
additional information to potential subjects about the possible future 
use of their information or biospecimens. This information will help 
subjects make informed decisions about whether to participate in a 
particular clinical investigation.
    The element of informed consent in the revised Common Rule at 45 
CFR 46.116(b)(9) requires that subjects be provided with one of two 
statements that address research that involves the collection of 
identifiable private information or identifiable biospecimens.\11\ 
Under the revised Common Rule, identifiers could be removed from 
information or biospecimens collected as part of a study and the 
information or specimens could then be used for some secondary research 
without informed consent or IRB review. The element of informed consent 
at 45 CFR 46.116(b)(9) would inform subjects of that possibility when 
applicable.
---------------------------------------------------------------------------

    \11\ This may be either: (1) a statement that identifiers may be 
removed from the identifiable private information or identifiable 
biospecimens, and the information or biospecimens may be used for 
future research studies or distributed to another investigator for 
future research studies, without obtaining additional informed 
consent from the subject or legally authorized representative if 
this might be a possibility or (2) a statement that the subject's 
information or biospecimens, even if the identifiers are removed, 
will not be used or distributed for future research.
---------------------------------------------------------------------------

    FDA's proposed new element would require a description of how 
information or biospecimens may be used for future research or 
distributed to another investigator for future research. While FDA's 
proposed element is not limited to the two situations addressed by the 
statements required under the corresponding element of the revised 
Common Rule, the research community would be able to develop informed 
consent forms and processes that comply with both sets of regulations. 
For example, if appropriate, an investigator may use one of the 
statements provided in the revised Common Rule to satisfy FDA's 
proposed requirement. When applicable, an investigator would also be 
required to provide a description that conveys to subjects the possible 
future use of their identifiable biospecimens or information that may 
not be stripped of identifiers.
    In addition, as noted above, Congress passed the Cures Act with a 
stated purpose of accelerating the discovery, development, and delivery 
of 21st century cures. FDA has been working to modernize its approach 
to evaluating innovative medical products as new technologies and 
sources of data create new options for generating and analyzing 
evidence regarding FDA-regulated products. Such technological advances 
may have the potential to, for example, streamline and improve the 
efficiency of clinical studies, but they may also raise new questions 
in the future about the applicability of certain FDA regulatory 
requirements, including requirements for informed consent. Therefore, 
we are concerned about the practicability of limiting this proposed 
element of informed consent to the two situations addressed by the 
statements required under the Common Rule at this time. FDA's proposal 
is intended to incorporate flexibility as to the description that an 
investigator would provide to each subject or the legally authorized 
representative to help ensure that subjects are informed regarding 
possible future uses of information and biospecimens collected from 
their participation in a clinical investigation as the ways in which 
information and biospecimens are used relevant to FDA-regulated 
products continue to evolve. We request public comment on whether FDA's 
proposed new basic element of informed consent at Sec.  50.25(a)(9) 
would provide adequate notice to potential subjects regarding the 
possible future research use of their information and biospecimens or 
whether the Common Rule's provision at 45 CFR 46.116(b)(9) would better 
inform potential subjects about the possible future use of their 
information and biospecimens in research. We further request public 
comment on whether the research community anticipates challenges in 
implementing FDA's proposed new element and whether an alternative 
approach could lessen such challenges.
    FDA is proposing to add three new additional elements of informed 
consent, Sec.  50.25(b)(7), (8), and (9), to harmonize with the revised 
Common Rule at 45 CFR 46.116(c)(7), (8), and (9), respectively. Section 
50.25(b)(7) would require a statement that the subject's biospecimens 
(even if identifiers are removed) may be used for commercial profit and 
whether the subject will or will not share in this commercial profit. 
Section 50.25(b)(8) would require a statement on whether clinically 
relevant research results, including individual research results, will 
be disclosed to subjects, and if so, under what conditions. Section 
50.25(b)(9) pertains to research involving biospecimens and would 
require that subjects be informed whether the research will (if known), 
or might, include whole genome sequencing (WGS). The preamble to the 
revised Common Rule noted that WGS generates an extremely large amount 
of information about people, including factors that will contribute to 
their future medical conditions. The Common Rule goes on to state 
``Given the unique implications of the information that can be 
developed through WGS, if it is either known that a specific research 
study will include this technique, or might include it, we believe that 
this aspect of the research must be disclosed to prospective subjects 
as part of the informed consent process.'' \12\ FDA agrees that it is 
important for prospective subjects to be informed when a clinical 
investigation involves or may involve WGS, and is, therefore, proposing 
to add this new element.
---------------------------------------------------------------------------

    \12\ 82 FR 7149 at 7216, January 19, 2017.
---------------------------------------------------------------------------

4. References to Federal, State, or Local Law
    We propose to revise Sec.  50.25(d) and (e) by adding a reference 
to tribal law passed by the official governing body of an American 
Indian or Alaska Native tribe, to clarify that references to Federal, 
State, or local law are intended to include tribal law. This proposed 
change would harmonize FDA regulations with the revised Common Rule at 
45 CFR 46.116(i) and (j).
5. Documentation of Informed Consent
    We propose to add a parenthetical to Sec.  50.27(a), to clarify 
that consent forms in an electronic format are an acceptable format and 
add the term ``informed consent'' before the term ``form'' to harmonize 
the regulatory text with the revised Common Rule at 45 CFR 46.117(a).
    We are proposing to revise Sec.  50.27(b)(1) and (2) to include 
references to a subject's legally authorized representative. We are 
proposing to reorder sentences and make other changes in Sec.  
50.27(b)(1) to clarify that the subject or legally authorized 
representative shall have adequate opportunity to read the informed 
consent form. We are proposing to revise Sec.  50.27(b)(2) to require 
that the key information required by Sec.  50.20 be presented first 
when using a short form written informed consent. These changes are 
being proposed to better inform potential subjects about participation 
in a clinical investigation, and to

[[Page 58739]]

harmonize with the revised Common Rule at 45 CFR 46.117(b)(1) and (2).
    FDA is not proposing to add the new provision found in the revised 
Common Rule at 45 CFR 46.116(g) at this time. This provision allows 
IRBs to approve a research proposal for which investigators obtain 
information or biospecimens without an individual's informed consent 
for the purpose of screening, recruiting, or determining eligibility of 
the prospective human subject or LAR if either of the following 
conditions are met: (1) the investigator will obtain information 
through oral or written communication with the prospective subject or 
LAR or (2) the investigator will obtain identifiable private 
information or identifiable biospecimens by accessing records or stored 
identifiable biospecimens.
    FDA's longstanding policy on preparatory activities to a clinical 
investigation is that some specific activities are not considered to 
fall within the definition of a clinical investigation, and therefore 
do not require IRB review or informed consent under FDA's regulations. 
For example, we generally have not considered performing a survey of 
patient records at a site to determine whether the site has a 
sufficient number of patients with the condition of interest for the 
clinical investigation to be feasible to require informed consent and 
IRB review. However, IRB review and informed consent would need to be 
obtained prior to initiation of any clinical screening procedure that 
is performed solely for the purpose of determining eligibility for a 
clinical investigation.\13\ We request comment on whether FDA's current 
policy adequately addresses screening, recruiting, or determining 
eligibility for an FDA-regulated clinical investigation, or if 
including the revised Common Rule provision at 45 CFR 46.116(g) would 
be useful for FDA-regulated clinical investigations. Furthermore, FDA 
is proposing to make grammatical corrections, updates to statutory 
references, and other minor editorial changes to part 50. Throughout 
part 50 a global change has been made to spell out references to ``the 
act'', to conform to current Federal Register format requirements. 
Table 2 contains a description of amendments that are unrelated to 
harmonization with the revised Common Rule.
---------------------------------------------------------------------------

    \13\ See FDA's guidance entitled, ``Screening Tests Prior to 
Study Enrollment, Guidance for Institutional Review Boards and 
Clinical Investigators,'' January 1998, available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/screening-tests-prior-study-enrollment.

 Table 2--Proposed Revisions to Part 50 Unrelated to Harmonization With
                         the Revised Common Rule
------------------------------------------------------------------------
         Section No.                        FDA proposes to:
------------------------------------------------------------------------
50.1(a)......................  Remove specific statutory provisions in
                                final sentence and make minor wording
                                changes.
50.3(b)(20) and 50.3(j)......  Update references to certain provisions
                                of the PHS Act.
50.3(b)(16)-(19), (23).......  Clarify that citations in this section of
                                the regulatory text are to the FD&C Act.
50.3(i)......................  Add a sentence to the definition of IRB
                                to state the primary purpose of IRB
                                review is to assure the protection of
                                the rights and welfare of human
                                subjects.
50.24(a)(6)..................  Revise the citation at the end of the
                                first sentence from ``Sec.   50.25'' to
                                ``this part'' to simplify the regulatory
                                text and ensure that both the informed
                                consent procedures and document are
                                consistent with part 50.
50.25(c).....................  Add heading to conform to current Federal
                                Register format requirements.
------------------------------------------------------------------------

    We propose to modify Sec.  50.1(a) to remove the list of statutory 
provisions in the final sentence because the scope of part 50 is 
already described in the provision. In addition, removing these 
provisions will delete certain out of date citations and eliminate the 
need to update statutory references in the future. Similarly, we 
propose to modify Sec.  50.3(b)(20) and (j) to remove outdated 
references to certain provisions of the PHS Act. We propose to clarify 
that references in Sec.  50.3(b)(16) through (19) and (23) are to 
sections of the FD&C Act.
    We propose to add the following sentence, ``The primary purpose of 
such review is to assure the protection of the rights and welfare of 
the human subjects'' to the definition of ``institutional review 
board'' at Sec.  50.3(i), to be consistent with our current definition 
of IRB at Sec.  56.102(g).
    We propose to revise the citation in Sec.  50.24(a)(6) from ``Sec.  
50.25'' to ``this part,'' to simplify the regulatory text, and to 
clarify that both the informed consent procedures and documents for 
studies conducted under Sec.  50.24 must be consistent with part 50.
    We also propose to add a heading to Sec.  50.25(c), ``Required 
statement in informed consent documents for applicable clinical 
trials,'' to conform to current Federal Register format requirements.

B. 21 CFR Part 56--Institutional Review Boards

    We propose to revise part 56 to modify provisions related to 
continuing review, add or modify definitions, and make clarifying 
editorial changes. FDA believes that these proposed changes will help 
modernize, clarify, and enhance both human subject protection and the 
IRB review process. Table 3 identifies sections in which FDA proposes 
to harmonize our regulatory requirements with language in the revised 
Common Rule.

                Table 3--Proposed Revisions to Part 56 To Harmonize With the Revised Common Rule
----------------------------------------------------------------------------------------------------------------
                                                                           Harmonizes with revised common rule
               Section No.                       FDA Proposes to:               section  (45 CFR part 46)
----------------------------------------------------------------------------------------------------------------
56.102(n)................................  Add a definition of          46.102(m).
                                            ``written or in writing''
                                            that includes both
                                            physical and electronic
                                            formats.
56.103(c)................................  Add a reference to tribal    46.101(f).
                                            law of American Indian or
                                            Alaska Native tribes to
                                            clarify that the reference
                                            to Federal, State, or
                                            local laws is intended to
                                            include tribal law; make
                                            minor editorial changes.

[[Page 58740]]

 
56.107(a)................................  Make minor changes to        46.107(a).
                                            characteristics of IRB
                                            members and the
                                            description of categories
                                            of subjects who are
                                            considered vulnerable.
56.107(b)................................  Delete Sec.   56.107(b)      46.107(a).
                                            because the requirement
                                            for IRB membership
                                            diversity would be
                                            included in Sec.
                                            56.107(a); redesignate
                                            remaining sections--see
                                            table 4.
56.108(a)(2).............................  Move IRB member list         46.108(a)(2).
                                            details from Sec.
                                            56.115(a)(5) to
                                            56.108(a)(2) and make
                                            minor editorial changes.
56.108(a)(3)(i)-(iii)....................  Make editorial changes to    46.108(a)(3)(i), (ii) and (iii).
                                            the requirements for IRB
                                            written procedures.
56.108(a)(4)(i)-(ii), 56.108(b)..........  Make editorial changes and   46.108(a)(4).
                                            redesignate the sections.
56.109(b)................................  Add ``or legally authorized  46.109(b).
                                            representatives, when
                                            appropriate'' to clarify
                                            that subjects or LARs must
                                            be given informed consent
                                            information in accordance
                                            with Sec.   50.25.
56.109(c)(3).............................  Add a new exception to the   46.117(c)(1) and (c)(1)(iii).
                                            requirement for
                                            documentation of informed
                                            consent in specific
                                            circumstances.
56.109(d)................................  Provide that LARs may also   46.117(c)(2).
                                            receive written
                                            statements, if required by
                                            the IRB, when
                                            documentation of informed
                                            consent is waived.
56.109(f)................................  Add reference to Sec.        46.109(e).
                                            56.109(g).
56.109(g)................................  Eliminate the requirement    46.109(f)(1)(iii).
                                            to conduct continuing
                                            review of research under
                                            certain circumstances.
56.110(b)................................  Remove parenthetical         46.110(b)(1)(ii).
                                            phrase, ``(of 1 year or
                                            less)''.
56.111(a)(3).............................  Revise the description of    46.111(a)(3).
                                            subjects who may be
                                            considered vulnerable.
56.111(a)(5).............................  Delete the phrase ``and to   46.111(a)(5).
                                            the extent required'' from
                                            the requirement to
                                            document informed consent
                                            in accordance with Sec.
                                            50.27.
56.111(b)................................  Revise the description of    46.111(b).
                                            subjects who are
                                            considered vulnerable.
56.115(a)(3).............................  Add a requirement to retain  46.115(a)(3).
                                            records of the rationale
                                            for continuing review of
                                            research that otherwise
                                            would not require
                                            continuing review under
                                            Sec.   56.109(g).
----------------------------------------------------------------------------------------------------------------

1. Definitions
    We are proposing to add a new definition, ``written or in 
writing'', at Sec.  56.102(n), which would harmonize with the 
definition in the revised Common Rule at 45 CFR 46.102(m). The new 
definition would include both paper and electronic formats, the latter 
of which are increasingly used to fulfill many of the documentation 
requirements that appear throughout the IRB and human subject 
protection regulations. Adding this definition would provide clarity to 
the regulated community that IRB records may be maintained in 
electronic formats.
2. Tribal Law and IRB Review
    We are proposing to add a reference to tribal law passed by the 
official governing body of an American Indian or Alaska Native tribe to 
clarify that the reference to Federal, State, or local laws or 
regulations, is intended to include tribal law. This proposed revision 
would also harmonize Sec.  56.103(c) with the revised Common Rule at 45 
CFR 46.101(f).
3. IRB Membership
    We are proposing to amend Sec.  56.107(a) to harmonize with the 
revised Common Rule's language at 45 CFR 46.107(a), which describes 
characteristics of IRB membership. We propose deleting Sec.  56.107(b), 
which requires IRBs to ensure that their membership not consist 
entirely of a single gender and prohibits IRB membership from being 
composed entirely of members of one profession. Section 56.107(b) is no 
longer necessary because it would be subsumed into proposed Sec.  
56.107(a), which would require that an IRB's membership reflects 
diversity of professional qualifications, and other factors including 
race, gender, and cultural backgrounds.
4. IRB Functions and Operations
    We propose moving the details about IRB membership rosters from 
Sec.  56.115(a)(5) to Sec.  56.108(a)(2) and making editorial changes 
to harmonize the language with the revised Common Rule at 45 CFR 
46.108(a)(2). We are also proposing editorial and technical revisions 
to Sec.  56.108, including redesignating some sections, to harmonize 
with the revised Common Rule.
5. IRB Review of Research
    We propose adding ``or legally authorized representative, when 
appropriate'' to Sec.  56.109(b), to clarify that subjects or legally 
authorized representatives must be given informed consent information 
in accordance with Sec.  50.25, and to harmonize with the revised 
Common Rule at 45 CFR 46.109(b).
    We propose adding new Sec.  56.109(c)(3) to add an exception to the 
requirement for documentation of informed consent, to harmonize with 
the revised Common Rule at 45 CFR 46.117 (c)(1)(iii). The new provision 
would allow the IRB to waive documentation of informed consent for a 
study that presents no more than minimal risk of harm to the subjects, 
if the subjects or legally authorized representatives are members of a 
distinct cultural group or community in which signing forms is not the 
norm, and there is an appropriate alternative mechanism for documenting 
that informed consent was obtained.
    We note that the revised Common Rule also retains an exception to 
the requirement for documentation of informed consent at 45 CFR 
46.117(c)(1)(i) for situations in which the only record linking the 
subject and the research would be the informed consent form and the 
principal risk would be potential harm resulting from a breach of 
confidentiality. FDA's regulations historically have not included this 
same exception, and we are not proposing to add it in this rulemaking 
because we do not believe it is relevant to FDA-regulated research. We 
are, however, requesting comment on whether this provision is relevant 
to FDA-regulated research and any examples of situations when it would 
be useful.
    We propose adding ``or legally authorized representatives'' to 
Sec.  56.109(d), to clarify that legally authorized representatives may 
also

[[Page 58741]]

receive written statements about the research, if required by the IRB, 
when documentation of informed consent is waived, and to harmonize with 
the revised Common Rule at 45 CFR 46.117(c)(2).
    We are proposing new Sec.  56.109(g), which would eliminate the 
requirement for an IRB to conduct continuing review of research, unless 
an IRB determines otherwise, that has progressed to the point that it 
involves only data analysis, including analysis of identifiable private 
information or identifiable biospecimens, and/or accessing followup 
clinical data from procedures that subjects would undergo as part of 
clinical care, to harmonize with the revised Common Rule at 45 CFR 
46.109(f)(1)(iii). In these circumstances, FDA believes that requiring 
continuing review would generally not provide added protection to human 
subjects, and therefore, would not be necessary. When the only 
remaining research activities are limited to analysis of data or 
biospecimens that are part of the IRB-approved study, there is little 
or no risk to human subjects that would be addressed by requiring 
continuing review. Furthermore, after all subjects have enrolled and 
completed the protocol-specified interventions and interactions 
(including required followup study visits) to support the study's 
objectives, a protocol may include a long-term followup phase during 
which subjects continue to be monitored as they undergo clinical care 
for their medical condition or disease by their healthcare provider. 
During this continued followup phase, information regarding long-term 
clinical outcomes may be obtained through accessing clinical data 
generated during the course of clinical care. This proposed rule would 
eliminate the requirement for continuing IRB review for this followup 
portion of the study, unless the IRB determines otherwise.\14\ This 
proposal to eliminate the requirement for continuing IRB review in 
certain circumstances would apply to FDA-regulated studies that are 
ongoing on the proposed effective date (see Section VI, Proposed 
Effective Date below). If any such ongoing studies were federally 
conducted or supported and also subject to the pre-2018 Requirements 
(see 45 CFR 46.101(l)(1), then the pre-2018 Requirements for continuing 
review would continue to apply to those studies.
---------------------------------------------------------------------------

    \14\ However, FDA would still receive annual reports from 
sponsors on the progress of such studies in accordance with 21 CFR 
312.33 and 812.150(b)(5)).
---------------------------------------------------------------------------

    The revised Common Rule contains two other provisions identifying 
circumstances in which continuing review would not be necessary at 45 
CFR 46.109(f)(1)(i) and (ii). We are not proposing to adopt the revised 
Common Rule provision at 45 CFR 46.109(f)(1)(i), which eliminates the 
requirement for an IRB to conduct continuing review of research that is 
eligible for expedited review in accordance with 45 CFR 46.110 unless 
the IRB determines otherwise. As described below, OHRP has clarified 
that, in order for research to qualify for expedited review under the 
current list of research eligible for expedited review referenced in 45 
CFR 46.110(a), a determination must still be made by an IRB that the 
specific circumstances of the proposed research involve no more than 
minimal risk to human subjects. It is not practicable for FDA to adopt 
this provision because continuing review for minimal risk FDA-regulated 
clinical investigations would provide meaningful protections to human 
subjects participating in such investigations. For example, as a study 
progresses, the analysis of risks to subjects receiving a FDA-regulated 
product may change based on adverse events that occur during the course 
of the study and that do not rise to the level of unanticipated 
problems involving risks to human subjects or otherwise require 
reporting to the IRB. Continued IRB oversight of such studies would 
offer added human subject protection to those participating in such 
investigations by enabling the IRB to assess whether there are any 
additional risks that present more than minimal risk to participants 
and require discussion and/or action. Furthermore, for clinical 
investigations that are subject to both FDA's human subject regulations 
and the revised Common Rule, the Common Rule provision at 45 CFR 
46.109(f)(1)(i) allows an IRB to determine that continuing review of 
research eligible for expedited review is required.
    Finally, we are not proposing to adopt provisions from the revised 
Common Rule related to limited IRB review at this time, including 45 
CFR 46.109(f)(1)(ii). As we continue to consider how other provisions 
of the revised Common Rule could be applied to FDA-regulated research, 
including the revised Common Rule's exemptions, we may take additional 
steps to harmonize with such provisions at a later time.
    In addition, as described below, we are proposing changes to the 
IDE regulations at Sec.  812.150(a)(3) and (b)(5) to align the IRB 
progress reporting requirements with these proposed changes to IRB 
continuing review requirements under part 56.
    We propose reordering and redesignating the remaining language in 
Sec.  56.109(f), and current Sec.  56.109(g) and (h) as Sec.  
56.109(g), (h), and (i), respectively.
6. Expedited Review
    FDA's current regulations under Sec.  56.110(a) state that FDA has 
established, and published in the Federal Register, a list of 
categories of research that may be reviewed by the IRB through an 
expedited review procedure (``expedited review list'').\15\ FDA is not 
proposing any changes to Sec.  56.110(a) at this time, and the 
categories of research included on the expedited review list referenced 
in Sec.  56.110(a) are identical to the categories of research included 
on the expedited review list referenced in 45 CFR 46.110(a) (``HHS 
Expedited Review List'').\16\ The revised Common Rule requires that the 
Secretary evaluate the HHS expedited review list at least every 8 years 
and amend it, as appropriate, after consultation with other Federal 
Departments and Agencies and after publication in the Federal Register 
for public comment (45 CFR 46.110(a)). We intend to participate in this 
process and will update our own expedited review list, as appropriate 
for FDA-regulated studies.
---------------------------------------------------------------------------

    \15\ See ``Protection of Human Subjects: Categories of Research 
That May Be Reviewed by the Institutional Review Board (IRB) Through 
an Expedited Review Procedure,'' 63 FR 60353, November 9, 1998.
    \16\ See ``Protection of Human Subjects: Categories of Research 
That May Be Reviewed by the Institutional Review Board (IRB) Through 
an Expedited Review Procedure,'' 63 FR 60364, November 9, 1998.
---------------------------------------------------------------------------

    As described in the revised Common Rule, an IRB may use the 
expedited review procedure to review studies that involve activities 
appearing on the expedited review list, unless the IRB reviewer 
determines that the studies involve more than minimal risk (see 45 CFR 
46.110(b)(1)(i)). OHRP has clarified that until a new list is 
finalized, the entire 1998 HHS Expedited Review List, including the 
``Applicability'' section, remains in effect for studies subject to the 
revised Common Rule.\17\ Under the current wording of the 
``Applicability'' section, to be eligible for expedited review research 
must present no more than minimal risk to subjects. Therefore,

[[Page 58742]]

application of the 1998 HHS Expedited Review List means that, in order 
for research to qualify for expedited review under the revised Common 
Rule, a determination must still be made that the specific 
circumstances of the proposed research involve no more than minimal 
risk to human subjects.
---------------------------------------------------------------------------

    \17\ See OHRP, Revised Common Rule Q&As: After January 21, 2019 
(the general compliance date for the revised Common Rule), is the 
1998 Expedited Review List still in effect for studies subject to 
the revised Common Rule?, https://www.hhs.gov/ohrp/education-and-outreach/revised-common-rule/revised-common-rule-q-and-a/index.html 
(accessed August 6, 2019).
---------------------------------------------------------------------------

    Under FDA's current regulations at Sec.  56.110(b)(1), an IRB may 
use the expedited review procedure to review ``[s]ome or all of the 
research appearing on the list and found by the reviewer(s) to involve 
no more than minimal risk.'' Because the HHS Expedited Review List, 
including its ``Applicability'' section, is still in effect and lists 
the same categories of research as FDA's expedited review list, IRBs 
will be able to use the same procedures to review research that may be 
reviewed via expedited review under the revised Common Rule and FDA's 
current regulations.
    We also note that the current expedited review list (63 FR 60353, 
November 9, 1998) describes categories of research that include FDA-
regulated clinical investigations that may involve more than minimal 
risk. For example, Category 1 from the current expedited review list 
describes clinical studies of drugs and medical devices that meet 
certain conditions, including those that do not require an IND or those 
for which an IDE application is not required. FDA does not believe that 
all drug and device studies that do not require an IND or an IDE 
application qualify as minimal risk. Given this, FDA does not presume 
all clinical investigations of drugs or medical devices that do not 
require an IND or an IDE application present no more than minimal risk 
to subjects. Category 4 also describes clinical studies using medical 
devices that may not qualify as minimal risk. Therefore, FDA is 
maintaining the requirement that the reviewer determine that the 
research involves no more than minimal risk and is only proposing a 
minor change to the regulatory text in current Sec.  56.110(b) at this 
time. We propose to remove the parenthetical phrase ``(of 1 year or 
less)'' from Sec.  56.110(b)(2) to harmonize with the revised Common 
Rule at 45 CFR 46.110(b)(1)(ii) because continuing review would not be 
required in certain circumstances unless the IRB determines otherwise 
(see Sec.  56.109(g)).
    As HHS evaluates and amends, as appropriate, its current expedited 
review list as described above and as required under 45 CFR 46.110(a), 
FDA intends to participate in the process and will update our own 
expedited review list as appropriate and consider if any related 
changes to our regulations are necessary.
7. Criteria for IRB Approval of Research
    We are proposing to add, at Sec.  56.111(a)(3) and (b), updated 
language consistent with the revised Common Rule, describing categories 
of subjects who are considered vulnerable to coercion or undue 
influence, specifically ``. . . children, prisoners, individuals with 
impaired decision-making capacity, or economically or educationally 
disadvantaged persons.'' This proposal, if finalized, also would 
harmonize these sections with the language in the revised Common Rule 
at 45 CFR 46.111(a)(3) and (b). To simplify our regulatory text, FDA is 
also proposing to delete the phrase ``to the extent required by'' from 
Sec.  56.111(a)(5), so that the requirement would read ``Informed 
consent will be appropriately documented or appropriately waived, in 
accordance with Sec.  50.27 of this chapter.'' FDA's proposed revision 
differs slightly from the revised Common Rule at 45 CFR 46.111(a)(5), 
which states that informed consent will be appropriately documented or 
appropriately waived in accordance with 45 CFR 46.117. We are not 
proposing to include the reference to waiver of documentation as this 
is addressed under Sec.  50.27.
8. IRB Review of Research
    We are proposing to add at Sec.  56.115(a)(3), language that would 
require the IRB to maintain a record of the rationale for conducting 
continuing review, if the IRB determines that continuing review of 
research is necessary (when the research otherwise would not require 
continuing review under Sec.  56.109(g)). This proposed change would 
also harmonize the regulations with the language in the revised Common 
Rule at 45 CFR 46.115(a)(3). The revised Common Rule includes a new 
recordkeeping requirement at 45 CFR 46.115(a)(8) related to changes 
made to the regulatory provision at 45 CFR 46.110(b)(1)(i) regarding 
review of research found on the HHS Expedited Review List. For the 
reasons described above, FDA is not proposing to make the same change 
to its expedited review provision at Sec.  56.110(b)(1) and, 
accordingly, is not proposing to add the related recordkeeping 
requirement.
    We are proposing to revise Sec.  56.115(a)(5) by moving the details 
about IRB membership rosters from that section to Sec.  56.108(a)(2), 
to harmonize the language with the revised Common Rule at 45 CFR 
46.115(a)(5) and 46.108(a)(2).
    Table 4 lists sections that will be moved, redesignated, or 
divided, with minor editorial changes to the regulatory text in some 
cases.

 Table 4--Proposed Revisions to Numbering for Regulatory Text in Part 56
------------------------------------------------------------------------
     Current section No.              Proposed revised section No.
------------------------------------------------------------------------
56.107(c)....................  56.107(b).
56.107(d)....................  56.107(c).
56.107(e)....................  56.107(d).
56.107(f)....................  56.107(e).
56.108.......................  Redesignated to begin with 56.108(a).
56.108(a)(1).................  56.108(a)(3)(i).
56.108(a)(2).................  56.108(a)(3)(ii).
56.108(a)(3).................  56.108(a)(3)(iii).
56.108(b)....................  56.108(a)(4).
56.108(c)....................  56.108(b).
56.109(f)....................  Divided into two sections, 56.109(f) and
                                (h).
56.109(g)....................  56.109(i).
56.109(h)....................  56.109(j).
------------------------------------------------------------------------

    FDA also proposes to make minor changes to the current regulatory 
text and to delete outdated or unnecessary regulatory text from part 56 
(see table 5). In addition, throughout part 56 a global change has been 
made to spell out references to ``the act'', to conform to current 
Federal Register format requirements.

[[Page 58743]]



  Table 5--Proposed Minor Changes to or Deletion of Regulatory Text in
                                 Part 56
------------------------------------------------------------------------
         Section No.                        FDA proposes to:
------------------------------------------------------------------------
56.102(b)(17)................  Remove outdated reference to the PHS Act,
                                add corresponding FD&C Act reference.
56.102(l)....................  Replace outdated references to sections
                                of the PHS Act.
56.103(a)....................  Delete the reference to 21 CFR part 813,
                                which was removed from FDA's regulations
                                in 1997.
56.109(h) (now 56.109(j))....  Delete the second sentence referring to
                                pediatric studies that were ongoing on
                                April 30, 2001, because it is no longer
                                needed.
56.110(b)....................  Changed reference to Sec.   56.108(c) to
                                Sec.   56.108(b) because of
                                redesignating of sections.
56.110(c)....................  Changed ``which'' to ``that'' in two
                                places.
56.115(a)(6).................  Revise the citation to written procedure
                                provisions to reflect redesignating.
56.121(c)....................  Delete ``in the Federal Register,''
                                because notices may now be posted on the
                                FDA website.
56.122.......................  Modify section title from ``revocation''
                                to ``disqualification,'' and clarify
                                that disqualification of an IRB is also
                                disclosable to the public.
------------------------------------------------------------------------

9. Disqualification of an IRB or Institution
    We are proposing to revise Sec.  56.121(c) by deleting the phrase 
``in the Federal Register'' from the last sentence. This proposed 
change would clarify that FDA is not limited to publishing 
disqualification notices in the Federal Register but may use other 
available and appropriate methods to apprise the public of IRB 
disqualification actions. For example, FDA now routinely posts such 
information on the Agency's website.\18\
---------------------------------------------------------------------------

    \18\ https://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ComplianceEnforcement/default.htm.
---------------------------------------------------------------------------

10. Public Disclosure of Information Regarding Disqualification
    We are proposing to revise Sec.  56.122 by modifying the section 
title to change ``revocation'' to ``disqualification,'' and clarify 
that FDA's determination of disqualification of an IRB, as well as an 
institution, is disclosable to the public under 21 CFR part 20.

C. 21 CFR Part 812--Investigational Device Exemptions

    We are proposing to revise Sec.  812.150(a)(3), that requires 
investigators to submit progress reports on the investigation to the 
sponsor, the monitor, and the reviewing IRB at regular intervals, but 
in no event less often than yearly. The proposed revisions would 
provide that such progress reports must be submitted to the reviewing 
IRB to the extent that continuing review is required by part 56. 
Elsewhere in this document, FDA is proposing to revise part 56 to 
eliminate the requirement for IRB continuing review of research under 
certain circumstances, and FDA does not believe that submission of 
progress reports to the IRB remains necessary when continuing review of 
the research by the IRB is not required. This proposed revision to 
Sec.  812.150(a)(3) is intended to provide consistency between the 
continuing review requirements under part 56 and the requirements for 
submission of IDE progress reports to the IRB.
    We also propose revising Sec.  812.150(b)(5), which currently 
provides, among other things, that sponsors must submit progress 
reports to all reviewing IRBs at regular intervals, and at least 
yearly. For the same reasons described above regarding Sec.  
812.150(a)(3), FDA is proposing to require sponsors to submit such 
progress reports to the reviewing IRB to the extent that continuing 
review is required by part 56. The sponsors of an IDE will continue to 
submit progress reports to FDA at regular intervals and at least yearly 
under Sec.  812.150(b)(5), and as may be requested under Sec.  
812.150(b)(10), regardless of whether there is continuing IRB review. 
FDA is proposing to maintain this reporting requirement for continued 
oversight of investigations that require submission of an IDE 
application to ensure the Agency receives information regarding the IDE 
investigation. The proposed rule maintains the requirement that 
sponsors of treatment IDEs submit semi-annual and annual progress 
reports to all reviewing IRBs and FDA in accordance with Sec. Sec.  
812.36(f) and 812.150(b)(5).
    FDA is not proposing to amend the requirements for treatment IDEs 
at Sec.  812.36(f), which require semi-annual progress reports to both 
FDA and the IRB(s) until a marketing application is filed. After filing 
of a marketing application, Sec.  812.36(f) requires progress reports 
to be submitted at least annually in accordance with the IDE 
regulations at Sec.  812.150(b)(5). Our proposed changes to Sec.  
812.150(b)(5) would require progress reports to be submitted to 
reviewing IRBs to the extent that continuing review is required by part 
56. As such, after filing of a marketing application, submission of 
annual progress reports for a treatment IDE to the reviewing IRB would 
be required only to the extent that continuing review is required under 
part 56.

VI. Proposed Effective Date

    FDA is proposing that the effective date of any final rule that 
issues based on this proposal would be 180 days from the date of 
publication of the final rule to allow the regulated community time to 
prepare to implement the proposed changes. FDA requests comment on this 
timeframe.
    In addition, FDA's goal is to minimize disruption to FDA-regulated 
studies that are ongoing when the proposed new requirements would 
become effective, and we are proposing an implementation strategy to 
address research initially approved by an IRB before the proposed 
effective date. For these studies, FDA would not intend to enforce 
compliance with the following proposed provisions:
     proposed new Sec.  50.20(d) through (e), which would, 
among other things, require informed consent to begin with a concise 
and focused presentation of ``key information'' and would require 
informed consent information to be organized and presented in certain 
ways;
     the proposed new basic and additional elements of informed 
consent at Sec.  50.25(a)(9) and (b)(7) through (9); and
     the proposed revision to Sec.  50.27(b)(2), which would 
require the key information required by Sec.  50.20 to be presented 
first to the subject or the subject's legally authorized representative 
when informed consent information is provided orally and documented 
using a short form.
    This approach reflects FDA's concern that, for research an IRB has 
approved before the proposed effective date, revising the already 
approved informed consent form and process to comply with the 
provisions identified above could cause unwarranted burden and, in some 
cases, delay research. However, nothing in this proposal would prevent 
sponsors and investigators from

[[Page 58744]]

updating the consent forms for research that was approved before the 
proposed effective date to comply with the above-listed provisions. We 
request comment on this proposed approach.

VII. Preliminary Economic Analysis of Impacts

A. Introduction

    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). 
This proposed rule has been designated an economically 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 estimated cost savings of the proposed rule are 
greater in magnitude than estimated costs, and because we do not expect 
the effects of the rule to affect entities by size, we propose to 
certify that the rule, if finalized, will not have a significant 
economic impact on a substantial number of small entities. However, as 
discussed in the Preliminary Economic Analysis of Impacts (Ref. 1), 
there is a lack of high quality, comprehensive data regarding the 
number of small and very small institutions associated with IRBs, as 
defined by revenue. We have prepared an initial regulatory flexibility 
analysis and are seeking comment on the data and assumptions used in 
that analysis.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $158 million, using the most current (2020) 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.

B. Summary of Costs and Benefits

    If finalized, the proposed rule would: (1) revise content, 
organization, and presentation of the information included in the 
informed consent form and process to facilitate a prospective subject's 
decision about whether to participate in a clinical investigation; (2) 
add new basic and additional elements of informed consent; (3) add a 
provision allowing IRBs to eliminate continuing review of some 
research; (4) revise IRB recordkeeping requirements for certain 
determinations related to the need for continuing review; and (5) add 
or modify some definitions. The rule also proposes to revise FDA's 
regulations IDEs (part 812) to clarify and update the requirements for 
submission of progress reports for clinical investigations of devices.
    The proposed rule would harmonize certain aspects of FDA's 
regulations on IRBs and informed consent processes, to the extent 
practicable and consistent with statutory provisions, with the 
requirements of the revised Common Rule in accordance with section 3023 
of the Cures Act. The proposed rule should reduce the costs of 
conducting clinical investigations by harmonizing informed consent and 
certain continuing review processes for FDA-regulated research with the 
revised Common Rule. The proposed rule will also generate costs that we 
estimate will be relatively smaller than expected cost savings in the 
form of additional time spent learning the rule, developing new 
informed consent documents in line with the rule, and revised 
recordkeeping requirements related to continuing review. We also expect 
qualitative benefits that we do not estimate explicitly due to data 
limitations, including increased efficiency of clinical investigations 
and medical product development and improved human subject knowledge by 
providing subjects with clearer clinical investigation information. 
Table 6 summarizes our estimates of the annualized costs and annualized 
benefits (in the form of cost savings) of the proposed rule.
    The benefits of the proposed rule take the form of quantified net 
cost savings (cost savings minus costs) and qualitative benefits. We 
estimate that the benefits of the proposed rule are approximately $68 
million annually in 2018 dollars, with a lower bound of approximately 
$22 million and an upper bound of approximately $249 million, 
discounted at 7 percent over 10 years. When discounted at 3 percent, 
estimated benefits are approximately $68 million annually, with a lower 
bound of approximately $22 million and an upper bound of approximately 
$249 million. We also expect quantitative benefits in the form of cost 
savings from increased efficiency in medical product innovation and in 
the form of improved human subject knowledge. We estimate that the 
costs of the proposed rule are approximately $1.4 million annually in 
2018 dollars, with a lower bound of approximately $0.7 million and an 
upper bound of approximately $3.0 million, discounted at 7 percent over 
10 years. When discounted at 3 percent, estimated costs are 
approximately $1.3 million annually, with a lower bound of 
approximately $0.6 million and an upper bound of approximately $2.6 
million. These estimates are summarized in table 6.

                                     Table 6--Summary of Benefits, Costs and Distributional Effects of Proposed Rule
                                                                       [millions$]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Units
                                          Primary       Low        High    ------------------------------------
               Category                  estimate    estimate    estimate      Year      Discount     Period                      Notes
                                                                              dollars    rate (%)     covered
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized Monetized millions/year         $68         $22        $249        2018           7          10  Benefits are Cost Savings.
                                                68          22         249        2018           3          10  Benefits are Cost Savings.
    Annualized Quantified.............  ..........  ..........  ..........  ..........           7  ..........
                                                                                                 3
                                       -----------------------------------------------------------------------------------------------------------------

[[Page 58745]]

 
    Qualitative.......................  Increased efficiency in medical
                                        product innovation and improved
                                        human subject knowledge by
                                        providing subjects with clearer
                                        information regarding clinical
                                                  investigations.
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized Monetized $millions/            1.4         0.7         3.0        2018           7          10
     year.                                     1.3         0.6         2.6        2018           3          10
    Annualized Quantified.............  ..........  ..........  ..........  ..........           7  ..........
                                                                                                 3
                                       -----------------------------------------------------------------------------------------------------------------
    Qualitative.......................
 
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
    Federal Annualized Monetized        ..........  ..........  ..........  ..........           7  ..........
     $millions/year.                                                                             3
                                       -----------------------------------------------------------------------------------------------------------------
    From/To...........................  From:
                                        To:
                                       -----------------------------------------------------------------------------------------------------------------
    Other Annualized Monetized          ..........  ..........  ..........  ..........           7  ..........
     $millions/year.                                                                             3
                                       -----------------------------------------------------------------------------------------------------------------
    From/To...........................  From:
                                        To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
    State, Local or Tribal Government:
    Small Business:
    Wages:
    Growth:
--------------------------------------------------------------------------------------------------------------------------------------------------------

    We have developed a comprehensive Preliminary Economic Analysis of 
Impacts that assesses the impacts of the proposed rule. The full 
preliminary analysis of economic impacts is available in the docket for 
this proposed rule (Ref. 1) and at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

VIII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(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.

IX. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). 
A description of these provisions is given in the Description sections 
of this document with an estimate of the recordkeeping and third-party 
disclosure burden associated with the proposed rule. Included in the 
estimate is the time for reviewing instructions, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing each collection of information.
    FDA invites comments on these topics: (1) whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

A. Protection of Human Subjects and Institutional Review Boards--Parts 
50 and 56 (OMB Control Number 0910-0130)

    Description: Provisions in part 50 provide for the protection of 
human subjects involved in FDA-regulated clinical investigations. 
Provisions in part 56 set forth requirements for the composition, 
operation, and responsibilities of an IRB. IRBs serve in an oversight 
capacity by reviewing, among other things, informed consent documents 
and protocols for FDA-regulated studies to make findings required to 
approve research and document IRB actions. If finalized, the proposed 
rule would revise FDA's current regulations in parts 50 and 56 related 
to informed consent, waiver of documentation of informed consent, and 
IRB continuing review.
1. Proposed Changes to Informed Consent Requirements (Part 50)
    Under FDA's existing regulations at part 50, investigators must 
obtain informed consent of subjects or their LARs before involving 
subjects in an FDA-regulated clinical investigation, typically through 
written consent forms reviewed and approved by an IRB and signed by the 
subject or LAR. FDA's current regulations at Sec. Sec.  50.23 and 50.24 
provide for exceptions from the requirement to obtain informed consent 
in certain narrow circumstances. The information collections associated 
with development, IRB approval, and documentation of informed consent 
in compliance with FDA's existing regulations at Sec. Sec.  50.25 and 
50.27 are currently approved under OMB control number 0910-0130.

[[Page 58746]]

    The proposed rule, if finalized, would revise provisions at 
Sec. Sec.  50.20, 50.25, and 50.27 regarding the content, organization, 
and presentation of information in the informed consent. Proposed Sec.  
50.20(e) would require informed consent to begin with a concise and 
focused presentation of the key information that is most likely to 
assist a prospective subject or legally authorized representative in 
understanding the reasons why one might or might not want to 
participate in the research. This part of informed consent would have 
to be organized and presented in a way that facilitates comprehension. 
The proposed rule would also add a new basic element of informed 
consent at proposed Sec.  50.25(a)(9) and three new additional elements 
of informed consent at proposed Sec.  50.25(b)(7) through (9). Finally, 
the proposed rule would revise Sec.  50.27(b)(2) to clarify that when a 
short form is used to document that the required elements of informed 
consent have been presented orally to the subject or LAR, the key 
information required by proposed Sec.  50.20 must be presented first to 
the subject or LAR. These proposed changes to FDA's informed consent 
requirements would help ensure that prospective subjects receive and 
understand information important to choosing whether to participate in 
a clinical investigation.
2. Proposed Changes to Requirements for IRB Waiver of Documentation of 
Informed Consent and Continuing Review (Part 56)
    FDA's existing regulations at Sec.  56.109(c) provide for an IRB to 
waive the requirements for documentation of informed consent in some 
circumstances. To harmonize with the revised Common Rule, proposed 
Sec.  56.109(c)(3) would allow an IRB to waive documentation of 
informed consent in an additional circumstance: if the IRB finds that 
the research presents no more than minimal risk of harm to the 
subjects, the subjects or LARs are members of a distinct cultural group 
or community in which signing forms is not the norm, and there is an 
appropriate alternative mechanism for documenting that informed consent 
was obtained. IRBs are already required to maintain adequate 
documentation of their activities under FDA regulations at Sec.  
56.115, including minutes of IRB meetings and records of continuing 
review activities. Those existing recordkeeping requirements are part 
of the information collection currently approved under OMB control 
number 0910-0130. We believe that proposed Sec.  56.109(c)(3) 
represents an unusual circumstance that would affect a limited number 
of IRBs and thus introduce minimal change in burden associated with IRB 
recordkeeping.
    FDA is also proposing changes to its requirements for continuing 
review to harmonize with the revised Common Rule, which are intended to 
reduce burden on IRBs and allow them to focus their resources on 
research that presents higher risk. Under proposed Sec.  56.109(g), 
unless an IRB determines otherwise, continuing review of research is 
not required for research that has progressed to the point that it 
involves only one or both of the following, which are part of the IRB-
approved study: (1) data analysis, including analysis of identifiable 
private information or identifiable biospecimens or (2) accessing 
followup clinical data from procedures that subjects would undergo as 
part of clinical care. In these circumstances, FDA believes that 
requiring continuing review would generally not provide added 
protection to human subjects, and, therefore, would not be necessary. 
If an IRB chooses to conduct continuing review for research that meets 
these criteria, the rationale for doing so must be documented according 
to proposed Sec.  56.115(a)(3).
    Description of Respondents: Respondents to the information 
collections include investigators that develop written informed consent 
materials for submission to an IRB and that present this informed 
consent information to subjects participating in FDA-regulated clinical 
investigations (table 7) and IRBs that review and approve FDA-regulated 
clinical investigations (table 8).
    We estimate the burden of the information collection as follows:

                                                  Table 7--Estimated Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
                                                  Number of      disclosures    Total  annual
                21 CFR section                   respondents         per         disclosures         Average burden  per disclosure         Total hours
                                                                 respondent
--------------------------------------------------------------------------------------------------------------------------------------------------------
50.20(e), 50.25, and 50.27--development of              4,122               1           4,122  2.5......................................          10,305
 written consent materials for submission to
 IRB.
50.25 and 50.27--disclosure of consent                  4,122             200         824,400  0.5 (30 minutes).........................         412,200
 information to subjects.
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................         422,505
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital or operating and maintenance costs associated with the information collection.

    Based on our review of information from ClinicalTrials.gov (https://clinicaltrials.gov/; accessed on March 8, 2018), we estimate that 
there are 4,122 new FDA-regulated clinical investigations per year. 
Table 7, row 1 provides our estimate of the annual burden respondents 
will incur for developing written consent materials for new clinical 
investigations. We do not anticipate that investigators will revise 
informed consent forms and processes to reflect the proposed revisions 
to Sec. Sec.  50.20(e), 50.25, and 50.27 for ongoing clinical trials 
that are approved by an IRB before the proposed effective date of the 
rule, and therefore, our estimate reflects burden we attribute to new 
clinical investigations. If the proposed rule is finalized, we estimate 
that for each new clinical investigation, one investigator will spend a 
total of 2.5 hours to develop written consent materials to submit for 
IRB approval in connection with a new clinical investigation to satisfy 
proposed and existing requirements under Sec. Sec.  50.20(e), 50.25, 
and 50.27 (table 7, row 1), including existing requirements already 
accounted for under OMB control number 0910-0130. This new total 
estimated time includes 0.5 hours for developing a written informed 
consent form or the written summary of what is said to the subject as 
required under Sec.  50.27(b)(2) in order to comply with the proposed 
new requirements at Sec. Sec.  50.20(e), 50.25(a)(9) and (b)(7) through 
(9), and 50.27(b)(2).
    The information collection approved under OMB control number 0910-
0130 pertains to developing and documenting informed consent in 
accordance with Sec. Sec.  50.25 and 50.27 and includes burden 
attributable to development and approval by an IRB of a site-specific 
informed consent document, and the documentation of informed consent, 
but

[[Page 58747]]

does not currently account for subsequent presentation of the informed 
consent information to subjects. We address this third-party disclosure 
in table 7, row 2, and seek its inclusion under control number 0910-
0130, to ensure clarity regarding the PRA approval status of the 
presentation of informed consent information to individual subjects in 
all FDA-regulated clinical investigations to which Sec. Sec.  50.25 and 
50.27 apply. Our ability to provide a precise estimate for this burden 
is limited by the significant variability in the size of clinical 
investigations, which can range from a few subjects to tens of 
thousands, and which thus affects the estimated average number of 
responses per respondent. In accordance with PRA regulations (5 CFR 
1320 at 1320.8(b)(3)(iii)), we provide our estimate in table 7, row 2 
of the annual average burden and invite comment on this estimate.

                                                   Table 8--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
                21 CFR section                    Number of      records per    Total  annual      Average  burden per  recordkeeping       Total hours
                                                recordkeepers   recordkeeper       records
--------------------------------------------------------------------------------------------------------------------------------------------------------
56.109(c)(3)--Waiver of documentation of                   25               1              25  0.25 (15 minutes)........................            6.25
 informed consent when subjects are members
 of a distinct cultural group in which
 signing forms is not the norm, research is
 no more than minimal risk, and appropriate
 mechanism for documenting that informed
 consent was obtained.
56.115(a)(3)--Documentation of rationale when             500               1             500  0.25 (15 minutes)........................             125
 conducting continuing review of research
 that otherwise would not require continuing
 review.
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................          131.25
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital or operating and maintenance costs associated with the information collection.

    We estimate that one percent of IRBs (25) will review one study 
annually to determine whether the subjects or their LARs are members of 
a distinct cultural group or community in which signing forms is not 
the norm, such that the IRB may waive documentation of informed consent 
under proposed Sec.  56.109(c)(3). We believe these IRBs are likely to 
document the findings required to approve the waiver in IRB meeting 
minutes (Sec.  56.115(a)(2)), although they could be documented 
elsewhere in IRB records. We estimate that this recordkeeping will 
require 15 minutes to complete, as reflected in table 8, row 1.
    We estimate that 500 IRBs will review one study annually that will 
be subject to the proposed requirement under Sec.  56.115(a)(3) to 
document the IRB's rationale for conducting continuing review of 
research that otherwise would not require continuing review under 
proposed Sec.  56.109(g). We estimate that the associated documentation 
will require 15 minutes to complete, as reflected in table 8, row 2.

B. Investigational Device Exemptions--Part 812 (OMB Control Number 
0910-0078)

    Description: Provisions in part 812 set forth procedures for the 
conduct of clinical investigations of devices and provide for the 
protection of human subjects involved in such investigations. Under 
FDA's existing regulations at Sec.  812.150(a)(3) and (b)(5), sponsors 
and investigators of device investigations are required, among other 
things, to submit progress reports to reviewing IRBs at regular 
intervals, but in no event less often than yearly. The proposed rule 
would revise Sec.  812.150(a)(3) and (b)(5) to require that such 
progress reports on clinical investigations of devices be submitted to 
the reviewing IRB to the extent that continuing review is required by 
part 56. Therefore, the proposed change would eliminate the need to 
submit progress reports to the reviewing IRB for non-significant risk 
and significant risk device studies when continuing review is no longer 
required under part 56. The proposed revisions to part 812 are intended 
to provide consistency between the proposed continuing review 
requirements under part 56 and the requirements for submission of IDE 
progress reports to IRBs.
    Description of Respondents: Respondents to the information 
collection are investigators for and sponsors of clinical 
investigations of devices.

                                    Table 9--Estimated Annual Third-Party Disclosure Burden Under 21 CFR Part 812 \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
                       21 CFR Part 812; IDEs                            Number of     disclosures per    Total annual   Average  burden    Total hours
                                                                       respondents       respondent      disclosures    per  disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
812.150; reports for non-significant risk studies..................               1                1                1                6                6
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital or operating and maintenance costs associated with the information collection.

    We characterize burden associated with progress reports under Sec.  
812.150 that are submitted from clinical investigators and sponsors to 
reviewing IRBs as a disclosure burden. As noted above, the proposed 
changes to Sec.  812.150(a)(3) and (b)(5) would eliminate the need to 
submit progress reports to reviewing IRBs for non-significant risk and 
significant risk devices studies when continuing review is no longer 
required under part 56. Therefore, there is no additional burden, and 
FDA believes these proposed changes may reduce the number of progress 
reports submitted to reviewing IRBs for device studies that progress to 
a point where continuing review is no longer required.
    We maintain our current estimate of one report annually for non-
significant risk device studies that do not require submission of an 
IDE application to FDA, and that preparing the report requires 6 hours, 
as approved under OMB control number 0910-0078. We note however, this 
is a longstanding estimate and invite comment specifically with regard 
to the number of progress reports sponsors and investigators anticipate 
submitting annually to reviewing IRBs and the burden associated with 
progress reports

[[Page 58748]]

under Sec.  812.150 for non-significant risk studies. We do not 
specifically estimate burden for progress reports to reviewing IRBs for 
significant risk studies under OMB control number 0910-0078 and 
therefore invite comment here on how, if at all, the proposed changes 
would affect the number of progress reports sponsors and investigators 
anticipate submitting annually to reviewing IRBs and overall burden for 
these significant risk studies.
    To ensure that comments on information collection are received, OMB 
recommends that written comments be submitted through https://www.reginfo.gov/public/do/PRAMain (see Addresses). All comments should 
be identified with the title of the information collection.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3407(d)), we have submitted the information collection provisions of 
this proposed rule to OMB for review. These information collection 
requirements will not be effective until FDA publishes a final rule, 
OMB approves the information collection requirements, and the rule goes 
into effect. FDA will announce OMB approval of these requirements in 
the Federal Register.

X. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13175. We have tentatively 
determined that the rule does not contain policies that would have a 
substantial direct effect on one or more Indian Tribes, on the 
relationship between the Federal Government and Indian Tribes, or on 
the distribution of power and responsibilities between the Federal 
Government and Indian Tribes. The Agency solicits comments from tribal 
officials on any potential impact on Indian Tribes from this proposed 
action.

XI. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
the proposed rule does not contain policies that have substantial 
direct effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. Accordingly, 
we conclude that the rule does not contain policies that have 
federalism implications as defined in the Executive Order and, 
consequently, a federalism summary impact statement is not required.

XII. Reference

    The following reference is on display at the Dockets Management 
Staff (see ADDRESSES) and is available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; it is also 
available electronically at https://www.regulations.gov. FDA has 
verified the website address, as of the date this document publishes in 
the Federal Register, but websites are subject to change over time.

1. FDA, Preliminary Economic Analysis of Impacts, Docket No. FDA-
2021-N-0286, available at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.

List of Subjects

21 CFR Part 50

    Human research subjects, Prisoners, Reporting and recordkeeping 
requirements, Safety.

21 CFR Part 56

    Human research subjects, Reporting and recordkeeping requirements, 
Safety.

21 CFR Part 812

    Health records, Medical devices, Medical research, 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, it is proposed that 21 CFR parts 50, 
56, and 812 be amended as follows:

PART 50--PROTECTION OF HUMAN SUBJECTS

0
1. The authority citation for part 50 is revised to read as follows:

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

0
2. In part 50, remove the words ``the act'' and add in their place 
``the Federal Food, Drug, and Cosmetic Act'' wherever they appear.
0
3. In Sec.  50.1, revise the last sentence of paragraph (a) to read as 
follows:


Sec.  50.1   Scope.

    (a) * * * Compliance with these parts is intended to protect the 
rights and safety of human subjects involved in such investigations.
* * * * *
0
4. In Sec.  50.3:
0
a. Remove and reserve paragraph (a);
0
b. Amend paragraphs (b)(16) through (19) by adding ``of the Federal 
Food, Drug, and Cosmetic Act'' at the end of each sentence;
0
c. Amend paragraph (b)(20) by removing ``section 358 of the Public 
Health Service Act'' and adding in its place ``section 534 of the 
Federal Food, Drug, and Cosmetic Act'';
0
d. Revise paragraphs (i), (j), and (l); and
0
e. Add paragraphs (t) through (w).
    The revisions and additions read as follows:


Sec.  50.3   Definitions.

* * * * *
    (i) Institutional review board (IRB) means any board, committee, or 
other group formally designated by an institution to review biomedical 
research involving humans as subjects, and to approve the initiation of 
and conduct periodic review of such research. The primary purpose of 
such review is to assure the protection of the rights and welfare of 
the human subjects. The term has the same meaning as the phrase 
institutional review committee as used in section 520(g) of the Federal 
Food, Drug, and Cosmetic Act.
    (j) Test article means any drug (including a biological product for 
human use), medical device for human use, human food additive, color 
additive, electronic product, or any other article subject to 
regulation under the Federal Food, Drug, and Cosmetic Act or under 
section 351 of the Public Health Service Act (42 U.S.C. 262).
* * * * *
    (l) Legally authorized representative means an individual or 
judicial or other body authorized under applicable law to consent on 
behalf of a prospective subject to the subject's participation in the 
procedure(s) involved in the research. If there is no applicable law 
addressing this issue, legally authorized representative means an 
individual recognized by institutional policy as acceptable for 
providing consent in the non-research context on behalf of the 
prospective subject to the subject's participation in the procedure(s) 
involved in the research.
* * * * *
    (t) Written or in writing means writing on a tangible medium (e.g., 
paper) or in an electronic format.
    (u) Private information includes information about behavior that 
occurs in a context in which an individual can reasonably expect that 
no observation or recording is taking place, and information that has 
been provided for specific purposes by an individual and that the 
individual can reasonably expect will not be made public (e.g., a 
medical record).
    (v) Identifiable private information is private information for 
which the

[[Page 58749]]

identity of the subject is or may readily be ascertained by the sponsor 
or investigator or associated with the information.
    (w) Identifiable biospecimen is a biospecimen for which the 
identity of the subject is or may readily be ascertained by the sponsor 
or investigator or associated with the biospecimen.
0
5. Revise Sec.  50.20 to read as follows:


Sec.  50.20   General requirements for informed consent.

    Except as provided in Sec. Sec.  50.23 and 50.24:
    (a) Before involving a human subject in research covered by these 
regulations, the investigator shall obtain the legally effective 
informed consent of the subject or the subject's legally authorized 
representative.
    (b) An investigator shall seek informed consent only under 
circumstances that provide the prospective subject or the legally 
authorized representative sufficient opportunity to discuss and 
consider whether or not to participate and that minimize the 
possibility of coercion or undue influence.
    (c) The information that is given to the subject or the legally 
authorized representative shall be in language understandable to the 
subject or the legally authorized representative.
    (d) The prospective subject or the legally authorized 
representative must be provided with the information that a reasonable 
person would want to have in order to make an informed decision about 
whether to participate, and an opportunity to discuss that information.
    (e)(1) Informed consent must begin with a concise and focused 
presentation of the key information that is most likely to assist a 
prospective subject or legally authorized representative in 
understanding the reasons why one might or might not want to 
participate in the research. This part of the informed consent must be 
organized and presented in a way that facilitates comprehension.
    (2) Informed consent as a whole must present information in 
sufficient detail relating to the research, and must be organized and 
presented in a way that does not merely provide lists of isolated 
facts, but rather facilitates the prospective subject's or legally 
authorized representative's understanding of the reasons why one might 
or might not want to participate.
    (f) No informed consent may include any exculpatory language 
through which the subject or the legally authorized representative is 
made to waive or appear to waive any of the subject's legal rights, or 
releases or appears to release the investigator, the sponsor, the 
institution, or its agents from liability for negligence.


Sec.  50.24   [Amended]

0
6. In Sec.  50.24, in paragraph (a)(6), remove ``Sec.  50.25'' at the 
end of the first sentence and add in its place ``this part''.
0
7. In Sec.  50.25:
0
a. Revise paragraphs (a) introductory text and (a)(3);
0
b. Add paragraph (a)(9);
0
c. Revise paragraphs (b) introductory text and (b)(1), (2), and (5);
0
d. Add paragraphs (b)(7) through (9);
0
e. Add a heading to paragraph (c); and
0
f. Revise paragraphs (d) and (e).
    The additions and revisions read as follows:


Sec.  50.25   Elements of informed consent.

    (a) Basic elements of informed consent. In seeking informed 
consent, the following information shall be provided to each subject or 
legally authorized representative:
* * * * *
    (3) A description of any benefits to the subject or to others that 
may reasonably be expected from the research.
* * * * *
    (9) A description of how information or biospecimens may be used 
for future research or distributed to another investigator for future 
research.
    (b) Additional elements of informed consent. When appropriate, one 
or more of the following elements of information shall also be provided 
to each subject or legally authorized representative:
    (1) A statement that the particular treatment or procedure may 
involve risks to the subject (or to the embryo or fetus, if the subject 
is or may become pregnant) that are currently unforeseeable.
    (2) Anticipated circumstances under which the subject's 
participation may be terminated by the investigator without regard to 
the subject's or legally authorized representative's consent.
* * * * *
    (5) A statement that significant new findings developed during the 
course of the research that may relate to the subject's willingness to 
continue participation will be provided to the subject.
* * * * *
    (7) A statement that the subject's biospecimens (even if 
identifiers are removed) may be used for commercial profit and whether 
the subject will or will not share in this commercial profit;
    (8) A statement regarding whether clinically relevant research 
results, including individual research results, will be disclosed to 
subjects, and if so, under what conditions; and
    (9) For research involving biospecimens, whether the research will 
(if known) or might include whole genome sequencing (i.e., sequencing 
of a human germline or somatic specimen with the intent to generate the 
genome or exome sequence of that specimen).
    (c) Required statement in informed consent documents for applicable 
clinical trials. *
    (d) Preemption. The informed consent requirements in these 
regulations are not intended to preempt any applicable Federal, State, 
or local laws (including tribal law passed by the official governing 
body of an American Indian or Alaska Native tribe) that require 
additional information to be disclosed in order for informed consent to 
be legally effective.
    (e) Emergency medical care. Nothing in these regulations is 
intended to limit the authority of a physician to provide emergency 
medical care to the extent the physician is permitted to do so under 
applicable Federal, State, or local law (including tribal law passed by 
the official governing body of an American Indian or Alaska Native 
tribe).
0
8. Revise Sec.  50.27 to read as follows:


Sec.  50.27   Documentation of informed consent.

    (a) Except as provided in Sec.  56.109(c) of this chapter, informed 
consent shall be documented by the use of a written consent form 
approved by the IRB and signed and dated (including in an electronic 
format) by the subject or the subject's legally authorized 
representative at the time of consent. A written copy shall be given to 
the person signing the informed consent form.
    (b) Except as provided in Sec.  56.109(c) of this chapter, the 
consent form may be either of the following:
    (1) A written informed consent form that meets the requirements of 
this part. The investigator shall give either the subject or the 
subject's legally authorized representative adequate opportunity to 
read the informed consent form before it is signed; alternatively, this 
form may be read to the subject or the subject's legally authorized 
representative.
    (2) A short form written informed consent form stating that the 
elements of informed consent required by Sec.  50.25 have been 
presented orally to the subject or the subject's legally authorized 
representative. The key information required by Sec.  50.20 must be 
presented first to the subject or the subject's legally authorized

[[Page 58750]]

representative, before other information, if any, is provided. The IRB 
shall approve a written summary of what is to be said to the subject or 
the legally authorized representative. When this method is used, there 
shall be a witness to the oral presentation. Only the short form itself 
is to be signed by the subject or the subject's legally authorized 
representative. However, the witness shall sign both the short form and 
a copy of the summary, and the person actually obtaining consent shall 
sign a copy of the summary. A copy of the summary shall be given to the 
subject or the subject's legally authorized representative, in addition 
to a copy of the short form.

PART 56--INSTITUTIONAL REVIEW BOARDS

0
9. The authority citation for part 56 continues 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
10. In part 56, remove the words ``the act'' and add in their place 
``the Federal Food, Drug, and Cosmetic Act''.
0
11. In Sec.  56.102, remove and reserve paragraph (a), revise 
paragraphs (b)(17) and (l), and add paragraph (n).
    The revisions and addition read as follows:


Sec.  56.102   Definitions.

* * * * *
    (b) * * *
    (17) Data and information regarding an electronic product submitted 
as part of the procedures for establishing, amending, or repealing a 
standard for such products, described in section 534 of the Federal 
Food, Drug, and Cosmetic Act.
* * * * *
    (l) Test article means any drug for human use, biological product 
for human use, medical device for human use, human food additive, color 
additive, electronic product, or any other article subject to 
regulation under the Federal Food, Drug, and Cosmetic Act or under 
section 351 of the Public Health Service Act (42 U.S.C. 262).
* * * * *
    (n) Written or in writing means writing on a tangible medium (e.g., 
paper) or in an electronic format.
0
12. In Sec.  56.103, revise paragraphs (a) and (c) to read as follows:


Sec.  56.103   Circumstances in which IRB review is required.

    (a) Except as provided in Sec. Sec.  56.104 and 56.105, any 
clinical investigation that must meet the requirements for prior 
submission (as required in parts 312 and 812 of this chapter) to the 
Food and Drug Administration shall not be initiated unless that 
investigation has been reviewed and approved by, and remains subject to 
continuing review by, an IRB meeting the requirements of this part.
* * * * *
    (c) Compliance with these regulations will in no way render 
inapplicable pertinent Federal, State, or local laws or regulations 
(including tribal law passed by the official governing body of an 
American Indian or Alaska Native tribe) that may otherwise be 
applicable and that provide additional protections for human subjects.
0
13. Revise Sec.  56.107 to read as follows:


Sec.  56.107   IRB membership.

    (a) Each IRB shall have at least five members, with varying 
backgrounds to promote complete and adequate review of research 
activities commonly conducted by the institution. The IRB shall be 
sufficiently qualified through the experience and expertise of its 
members (professional competence), and the diversity of its members, 
including race, gender, cultural backgrounds, and sensitivity to such 
issues as community attitudes, to promote respect for its advice and 
counsel in safeguarding the rights and welfare of human subjects. The 
IRB shall be able to ascertain the acceptability of proposed research 
in terms of institutional commitments (including policies and 
resources) and regulations, applicable law, and standards of 
professional conduct and practice. The IRB shall therefore include 
persons knowledgeable in these areas. If an IRB regularly reviews 
research that involves a category of subjects that is vulnerable to 
coercion or undue influence, such as children, prisoners, individuals 
with impaired decision-making capacity, or economically or 
educationally disadvantaged persons, consideration shall be given to 
the inclusion of one or more individuals who are knowledgeable about 
and experienced in working with these categories of subjects.
    (b) Each IRB shall include at least one member whose primary 
concerns are in scientific areas and at least one member whose primary 
concerns are in nonscientific areas.
    (c) Each IRB shall include at least one member who is not otherwise 
affiliated with the institution and who is not part of the immediate 
family of a person who is affiliated with the institution.
    (d) No IRB may have a member participate in the IRB's initial or 
continuing review of any project in which the member has a conflicting 
interest, except to provide information requested by the IRB.
    (e) An IRB may, in its discretion, invite individuals with 
competence in special areas to assist in the review of complex issues 
that require expertise beyond or in addition to that available on the 
IRB. These individuals may not vote with the IRB.
0
14. Revise Sec.  56.108 to read as follows:


Sec.  56.108   IRB functions and operations.

    (a) In order to fulfill the requirements of these regulations, each 
IRB shall:
    (1) [Reserved]
    (2) Prepare and maintain a current list of the IRB members 
identified by name; earned degrees; representative capacity; 
indications of experience such as board certifications or licenses 
sufficient to describe each member's chief anticipated contributions to 
IRB deliberations; and any employment or other relationship between 
each member and the institution, for example, full-time employee, part-
time employee, member of governing panel or board, stockholder, paid or 
unpaid consultant;
    (3) Establish and follow written procedures for:
    (i) Conducting its initial and continuing review of research and 
for reporting its findings and actions to the investigator and the 
institution;
    (ii) Determining which projects require review more often than 
annually and which projects need verification from sources other than 
the investigator that no material changes have occurred since previous 
IRB review;
    (iii) Ensuring prompt reporting to the IRB of proposed changes in a 
research activity; and for ensuring that investigators will conduct the 
research activity in accordance with the terms of the IRB approval 
until any proposed changes have been reviewed and approved by the IRB, 
except when necessary to eliminate apparent immediate hazards to the 
subject.
    (4) Establish and follow written procedures for ensuring prompt 
reporting to the IRB, appropriate institutional officials, and the Food 
and Drug Administration of:
    (i) Any unanticipated problems involving risks to subjects or 
others, or any serious or continuing noncompliance with these 
regulations or the requirements or determinations of the IRB; and
    (ii) any suspension or termination of IRB approval.
    (b) Except when an expedited review procedure is used (as described 
in Sec.  56.110), an IRB must review proposed research at convened 
meetings at which

[[Page 58751]]

a majority of the members of the IRB are present, including at least 
one member whose primary concerns are in nonscientific areas. In order 
for the research to be approved, it shall receive the approval of a 
majority of those members present at the meeting.
0
15. In Sec.  56.109:
0
a. Revise paragraph (b);
0
b. Add paragraph (c)(3);
0
c. Revise paragraphs (d) and (f);
0
d. Redesignate paragraphs (g) and (h) as paragraphs (i) and (j), 
respectively;
0
e. Add new paragraphs (g) and (h); and
0
f. Revise newly redesignated paragraphs (i) and (j).
    The revisions and additions read as follows:


Sec.  56.109   IRB review of research.

* * * * *
    (b) An IRB shall require that information given to subjects or 
legally authorized representatives, when appropriate, as part of 
informed consent is in accordance with Sec.  50.25 of this chapter. The 
IRB may require that information, in addition to that specifically 
mentioned in Sec.  50.25 of this chapter, be given to the subjects when 
in the IRB's judgment the information would meaningfully add to the 
protection of the rights and welfare of subjects.
    (c) * * *
    (3) The IRB may waive documentation of informed consent if it finds 
that the subjects or legally authorized representatives are members of 
a distinct cultural group or community in which signing forms is not 
the norm, that the research presents no more than minimal risk of harm 
to subjects, and provided there is an appropriate alternative mechanism 
for documenting that informed consent was obtained.
    (d) In cases where the documentation requirement is waived under 
paragraph (c)(1) or (3) of this section, the IRB may require the 
investigator to provide subjects or legally authorized representatives 
with a written statement regarding the research.
* * * * *
    (f) An IRB shall conduct continuing review of research covered by 
these regulations at intervals appropriate to the degree of risk, but 
not less than once per year, except as described in paragraph (g) of 
this section.
    (g) Unless an IRB determines otherwise, continuing review of 
research is not required for research that has progressed to the point 
that it involves only one or both of the following, which are part of 
the IRB-approved study:
    (1) Data analysis, including analysis of identifiable private 
information or identifiable biospecimens, or
    (2) Accessing followup clinical data from procedures that subjects 
would undergo as part of clinical care.
    (h) An IRB shall have authority to observe or have a third party 
observe the consent process and the research.
    (i) An IRB shall provide in writing to the sponsor of research 
involving an exception to informed consent under Sec.  50.24 of this 
chapter a copy of information that has been publicly disclosed under 
Sec.  50.24(a)(7)(ii) and (iii) of this chapter. The IRB shall provide 
this information to the sponsor promptly so that the sponsor is aware 
that such disclosure has occurred. Upon receipt, the sponsor shall 
provide copies of the information disclosed to FDA.
    (j) When some or all of the subjects in a study are children, an 
IRB must determine that the research study is in compliance with part 
50, subpart D of this chapter, at the time of its initial review of the 
research.
0
16. In Sec.  56.110, revise paragraphs (b) and (c) to read as follows:


Sec.  56.110   Expedited review procedures for certain kinds of 
research involving no more than minimal risk, and for minor changes in 
approved research.

* * * * *
    (b)(1) An IRB may use the expedited review procedure to review 
either or both of the following:
    (i) Some or all of the research appearing on the list described in 
paragraph (a) of this section and found by the reviewer(s) to involve 
no more than minimal risk;
    (ii) Minor changes in previously approved research during the 
period for which approval is authorized.
    (2) Under an expedited review procedure, the review may be carried 
out by the IRB chairperson or by one or more experienced reviewers 
designated by the IRB chairperson from among the members of the IRB. In 
reviewing the research, the reviewers may exercise all of the 
authorities of the IRB except that the reviewers may not disapprove the 
research. A research activity may be disapproved only after review in 
accordance with the nonexpedited review procedure set forth in Sec.  
56.108(b).
    (c) Each IRB that uses an expedited review procedure shall adopt a 
method for keeping all members advised of research proposals that have 
been approved under the procedure.
* * * * *
0
17. In Sec.  56.111, revise paragraphs (a)(1), (3), and (5) through (7) 
and (b) to read as follows:


Sec.  56.111   Criteria for IRB approval of research.

    (a) * * *
    (1) Risks to subjects are minimized:
    (i) By using procedures that are consistent with sound research 
design and that do not unnecessarily expose subjects to risk and
    (ii) Whenever appropriate, by using procedures already being 
performed on the subjects for diagnostic or treatment purposes.
* * * * *
    (3) Selection of subjects is equitable. In making this assessment 
the IRB should take into account the purposes of the research and the 
setting in which the research will be conducted. The IRB should be 
particularly cognizant of the special problems of research that 
involves a category of subjects who are vulnerable to coercion or undue 
influence, such as children, prisoners, individuals with impaired 
decision-making capacity, or economically or educationally 
disadvantaged persons.
* * * * *
    (5) Informed consent will be appropriately documented or 
appropriately waived, in accordance with Sec.  50.27 of this chapter.
    (6) When appropriate, the research plan makes adequate provision 
for monitoring the data collected to ensure the safety of subjects.
    (7) When appropriate, there are adequate provisions to protect the 
privacy of subjects and to maintain the confidentiality of data.
    (b) When some or all of the subjects are likely to be vulnerable to 
coercion or undue influence, such as children, prisoners, individuals 
with impaired decision-making capacity, or economically or 
educationally disadvantaged persons, additional safeguards have been 
included in the study to protect the rights and welfare of these 
subjects.
* * * * *
0
18. In Sec.  56.115, revise paragraphs (a)(3), (5), and (6) and (b) to 
read as follows:


Sec.  56.115   IRB records.

    (a) * * *
    (3) Records of continuing review activities, including the 
rationale for conducting continuing review of research that otherwise 
would not require continuing review as described in Sec.  56.109(g).
* * * * *
    (5) A list of IRB members in the same detail as Sec.  56.108(a)(2).
    (6) Written procedures for the IRB as required by Sec.  
56.108(a)(3) and (4).
* * * * *

[[Page 58752]]

    (b) The records required by this regulation shall be retained for 
at least 3 years after completion of the research. The institution or 
IRB may maintain the records in printed form or electronically. All 
records shall be accessible for inspection and copying by authorized 
representatives of the Food and Drug Administration at reasonable times 
and in a reasonable manner.
* * * * *
0
19. In Sec.  56.121, revise the last sentence in paragraph (c) to read 
as follows:


Sec.  56.121   Disqualification of an IRB or an institution.

* * * * *
    (c) * * * In addition, the Agency may elect to publish a notice of 
its action.
* * * * *
0
20. Revise Sec.  56.122 to read as follows:


Sec.  56.122   Public disclosure of information regarding 
disqualification.

    A determination that FDA has disqualified an IRB or an institution 
and the administrative record regarding that determination are 
disclosable to the public under part 20 of this chapter.

PART 812--INVESTIGATIONAL DEVICE EXEMPTIONS

0
21. The authority citation for part 812 is revised to read as follows:

    Authority:  21 U.S.C. 331, 351, 352, 353, 355, 360, 360c-360f, 
360h-360j, 360hh-360pp, 360rr-360ss, 360bbb-8b, 371, 372, 374, 379e, 
381, 382; 42 U.S.C. 216, 241, 262.

0
22. In Sec.  812.150, revise paragraphs (a)(3) and (b)(5) to read as 
follows:


Sec.  812.150   Reports.

    (a) * * *
    (3) Progress. An investigator shall submit progress reports on the 
investigation to the sponsor, the monitor, and the reviewing IRB at 
regular intervals, but in no event less often than yearly. Such 
progress reports shall be submitted to the reviewing IRB to the extent 
that continuing review is required by part 56 of this chapter.
* * * * *
    (b) * * *
    (5) Progress reports. At regular intervals, and at least yearly, a 
sponsor shall submit progress reports to all reviewing IRBs. Such 
progress reports shall be submitted to reviewing IRBs to the extent 
that continuing review is required by part 56 of this chapter. In the 
case of a significant risk device, a sponsor shall submit progress 
reports to FDA at regular intervals, and at least yearly. A sponsor of 
a treatment IDE shall submit semiannual progress reports to all 
reviewing IRBs and FDA in accordance with Sec.  812.36(f) and annual 
progress reports in accordance with this section.
* * * * *

    Dated: September 23, 2022.
Robert M. Califf,
Commissioner of Food and Drugs.
[FR Doc. 2022-21088 Filed 9-27-22; 8:45 am]
BILLING CODE 4164-01-P


