[Federal Register Volume 74, Number 42 (Thursday, March 5, 2009)]
[Proposed Rules]
[Pages 9578-9583]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-4628]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

45 CFR Part 46


Office for Human Research Protections; Institutional Review 
Boards

AGENCY: Department of Health and Human Services, Office of the 
Secretary, Office of Public Health and Science, Office for Human 
Research Protections.

ACTION: Advanced notice of proposed rulemaking; request for comments.

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SUMMARY: The Office for Human Research Protections (OHRP), Office of 
Public Health and Science is seeking information and comments on 
whether OHRP should pursue a notice of proposed rulemaking (NPRM) to 
enable OHRP to hold institutional review boards (IRB) and the 
institutions or organizations operating the IRBs, hereafter referred to 
as the IRB organizations (IORG), directly accountable for meeting 
certain regulatory requirements of the Department of Health and Human 
Services (HHS) regulations for the protection of human subjects. OHRP 
is contemplating this regulatory change to encourage institutions to 
rely on IRBs that are operated by another institution or organization, 
when appropriate. Historically, OHRP has only enforced compliance with 
45 CFR part 46 through the institutions that were engaged in human 
subjects research. This has been the case even in circumstances when a 
regulatory violation was directly related to the responsibilities of an 
external IRB that was designated on the engaged institution's assurance 
of compliance with OHRP. OHRP is considering whether to pursue a 
regulatory change that would enable the Department to hold IRBs and 
IORGs directly accountable for compliance with the provisions of 45 CFR 
part 46 that relate to an IRB's or IORG's responsibilities. OHRP 
believes that such a regulatory change in its enforcement authority may 
address one of the main disincentives institutions have cited as 
inhibiting them from exercising the regulatory flexibility that 
currently permits institutions to implement a variety of cooperative 
review arrangements and to rely on the review of an IRB operated by 
another institution or organization. If institutions become more 
willing to rely on cooperative review arrangements and on review of 
IRBs operated by other institutions or organizations, OHRP believes 
that this will reduce administrative burdens such as the time 
associated with IRB review for multi-site studies, the time devoted by 
IRB staff and investigators to duplicative IRB review, and the time and 
personnel costs associated with operating an IRB for those institutions 
that choose not to establish an internal IRB--without diminishing human 
subject protections. This request for information and comments stems 
from interest in this issue from the Secretary's Advisory Committee on 
Human Research Protections (SACHRP) and others, as well as two meetings 
on alternative IRB models that OHRP co-sponsored in November 2005 and 
November 2006 along with the National Institutes of Health (NIH), the 
Association of American Medical Colleges (AAMC), and the American 
Society of Clinical Oncology (ASCO).

DATES: Submit written or electronic information and comments by June 3, 
2009.

ADDRESSES: You may submit comments by any of the following methods:
    <bullet> E-mail: <a href="/cdn-cgi/l/email-protection#0b4259496a6868647e657f6a696267627f724b636378256c647d"><span class="__cf_email__" data-cfemail="ffb6adbd9e9c9c908a918b9e9d9693968b86bf97978cd1989089">[email protected]</span></a>. Include ``IRB 
Accountability RFI'' in the subject line.
    <bullet> Fax: 301-402-2071.
    <bullet> Mail/Hand Delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Julie Kaneshiro, OHRP, 1101 Wootton Parkway, Suite 200, 
Rockville, MD 20852.
    Comments received within the comment period, including any personal 
information provided, will be made available to the public upon 
request.

FOR FURTHER INFORMATION CONTACT: Julie Kaneshiro, OHRP, 1101 Wootton 
Parkway, Suite 200, Rockville, MD 20852; 240-453-6900; e-mail 
<a href="/cdn-cgi/l/email-protection#a9c3dcc5c0cc87c2c8c7ccdac1c0dbc6e9c1c1da87cec6df"><span class="__cf_email__" data-cfemail="c7adb2abaea2e9aca6a9a2b4afaeb5a887afafb4e9a0a8b1">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

I. Background

    HHS, through OHRP, regulates research involving human subjects 
conducted or supported by HHS in regulations codified at 45 CFR part 
46. The HHS regulations at 45 CFR part 46 identify requirements that 
pertain to several different entities, including the IRB and the 
institution engaged in non-exempt human subjects research. The IRB is 
an administrative body that takes the form of a board, committee, or 
group, and is responsible for conducting initial and continuing review 
of research involving human subjects. The IRB must have authority to 
approve, require modification in (in order to secure approval), or 
disapprove all research activities covered by the HHS regulations (45 
CFR 46.109(a)). An IRB's primary purpose in reviewing research is to 
ensure the protection of the rights and welfare of human research 
subjects.

Requirements for an Assurance of Compliance

    The HHS regulations for the protection of human subjects require 
that each institution engaged in non-exempt human subjects research 
conducted or supported by HHS provide a written assurance satisfactory 
to the Secretary of Health and Human Services that it will comply with 
the requirements of the HHS regulations (45 CFR 46.103(a)). OHRP 
reviews and approves such assurances on behalf of HHS. The Federalwide 
Assurance (FWA) is now the only type of assurance accepted and approved 
by OHRP. An FWA commits the entire institution (including institutional 
officials, IRBs designated in the assurance, research investigators, 
and all other employees or agents) to compliance with the HHS 
regulations whenever the institution is engaged in HHS-conducted or

[[Page 9579]]

-supported human subjects research. In addition, domestic institutions 
may voluntarily extend their FWA to cover all human subjects research 
at their institution regardless of the source of support for the 
particular research activity.
    Among other things, an institution's assurance of compliance must 
designate all of the IRBs that the institution will rely upon for the 
review of any research covered by its assurance (45 CFR 46.103(b)(2)). 
For each designated IRB, a list of IRB members identified by name, 
earned degrees, representative capacity, experience, and any employment 
or other relationship with the institution must be submitted to OHRP 
(45 CFR 46.103(b)(3)). The HHS regulations at 45 CFR part 46 provide an 
institution with significant flexibility in designating the IRBs that 
will review research under the institution's FWA. Options available to 
the institution include:
    <bullet> Designating on its FWA one or more IRBs that are operated 
by the institution (sometimes referred to as ``local'' or ``internal'' 
IRBs; hereafter referred to as ``internal IRBs''); and
    <bullet> Designating on its FWA one or more IRBs operated by other 
institutions or commercial or independent IRBs (hereafter referred to 
as ``external IRBs'').
    As stated in the Terms of Assurance for the FWA (see http://www.hhs.gov/ohrp/humansubjects/assurance/filasurt.htm), for each 
external IRB designated on an institution's FWA, an IRB Authorization 
Agreement must be executed:

    Any designation under this Assurance of another Institution's 
IRB or an independent IRB must be documented by a written agreement 
between the Institution and the IRB organization outlining their 
relationship and include a commitment that the designated IRB will 
adhere to the requirements of this Assurance. OHRP's sample IRB 
Authorization Agreement may be used for such purpose or the two 
organizations may develop their own agreement. This agreement should 
be kept on file at both organizations and made available to OHRP 
upon request.

    OHRP provides an example of an IRB Authorization Agreement at 
http://www.hhs.gov/ohrp/humansubjects/assurance/iprotsup.rtf. The 
agreement may be written to cover one research project, or to cover 
multiple research projects on a case-by-case basis, or to cover a class 
of research projects. This agreement will sometimes include a 
description of which regulatory requirements each party will be 
responsible for; e.g., reporting unanticipated problems involving risks 
to subjects or others (45 CFR 46.103(b)(5)) or the maintenance of IRB 
records (45 CFR 46.115).

Requirements for IRB Registration

    Before an IRB may be designated on an institution's FWA, the IRB 
must be registered with OHRP. For more information on IRB registration 
see http://www.hhs.gov/ohrp/assurances/.
    OHRP has been operating a system of IRB registration since December 
2000, which was initiated in response to a 1998 HHS Office of Inspector 
General recommendation that all IRBs register with the Federal 
government on a regular basis as part of an effort to develop a more 
streamlined, coordinated, and probing means of assessing IRB 
performance and to enhance the Federal government's ability to identify 
and respond to emerging problems.
    The OHRP IRB registration system was designed to collect 
information required under the HHS human subjects protection 
regulations at 45 CFR 46.103, as well as additional information that is 
provided voluntarily by institutions or IRBs regarding the 
accreditation status of the institution or IRB organization, the total 
numbers of active research protocols reviewed by the IRB (including 
protocols supported by other Federal departments or agencies) and the 
nature of those protocols, and IRB staffing.
    On July 6, 2004, OHRP published in the Federal Register a Notice of 
Proposed Rulemaking (NPRM) seeking public comment on changes to the 
current IRB registration system administered by OHRP (69 FR 40584). 
OHRP proposed to amend the HHS human subjects protection regulations at 
45 CFR part 46 by adding an additional subpart, entitled ``Registration 
of Institutional Review Boards.'' Under the proposed new subpart, for 
any IRB designated under an FWA that reviews human subjects research 
conducted or supported by HHS, most of the information, including the 
information that previously was provided on a voluntary basis, listed 
on the current OHRP IRB registration form would have to be submitted to 
OHRP. By requiring such information to be provided for all IRBs being 
registered, OHRP's IRB registration requirements would become 
substantially consistent with requirements for IRB registration that 
were simultaneously proposed by FDA (69 FR 40556).
    After taking into consideration the comments received during the 
public comment period, OHRP and FDA issued separate final IRB 
registration rules on January 15, 2009, that will become effective on 
July 14, 2009 (74 FR 2399; 74 FR 2358). OHRP's and FDA's IRB 
registration rules are compatible and largely consistent with one 
another. Under these final rules there will be a single registration 
system, accessible on the OHRP Web site, in which all IRBs that review 
research conducted or supported by HHS or clinical investigations 
regulated by FDA will need to be registered.

Enforcement Authority

    Section 289 of the Public Health Service Act authorizes OHRP to, on 
behalf of HHS, establish a compliance oversight process regarding 
violations of the rights of human subjects of research conducted or 
supported by HHS. Pursuant to this authority, OHRP may receive reports 
of such violations and take appropriate action.
    OHRP also derives compliance oversight authority from the 
previously discussed provisions of the HHS regulations at 45 CFR 
46.103(a) and its implementation of the FWA.
    Unlike the FDA regulations pertaining to IRBs, which explicitly 
include compliance oversight provisions at subpart E of 21 CFR part 56, 
the HHS regulations at 45 CFR part 46 do not include provisions 
specifically addressing IRB or IORG compliance with the regulatory 
requirements.

II. History of OHRP Compliance Oversight and the Changing Research 
Environment

    Historically, OHRP (and its predecessor office, the Office for 
Protection from Research Risks) has only enforced compliance with 45 
CFR part 46 through the institutions that were engaged in human 
subjects research. This has been the case even in circumstances when 
the regulatory violation was directly related to the responsibilities 
of an external IRB that was designated on the engaged institution's 
assurance of compliance with OHRP. Therefore, when OHRP received an 
allegation or indication of a regulatory violation on the part of an 
external IRB related to research to which the HHS regulations apply, 
OHRP has directed its compliance oversight evaluations and enforcement 
actions to the relevant FWA-holding institutions, not the external IRB 
or IORG at issue. When the HHS regulations related to IRB review last 
underwent a substantive revision on June 18, 1991 (56 FR 28003), few 
institutions were designating external IRBs to review research 
conducted under their assurances of compliance, in part because single 
site studies were more common than they are today, and it was more 
common for HHS-supported

[[Page 9580]]

research to be conducted by large academic medical centers that had 
their own internal IRBs. Therefore, there was no perceived need to hold 
IRBs or IORGs directly accountable for meeting any of the requirements 
of the HHS regulations at 45 CFR part 46. However, as HHS support for 
multi-site studies has increased, and previously non-traditional 
research settings, such as community hospitals and medical clinics, 
have become frequent research sites, the research community has looked 
for ways to make IRB review more effective and efficient.

III. Current Regulatory Flexibilities for IRB Review Arrangements

    The regulations offer institutions significant flexibility to 
implement a variety of cooperative review arrangements as permitted 
under 45 CFR 46.114. In addition, this flexibility is facilitated by 
the ability of institutions to designate external IRBs on their FWAs 
that will be responsible for the review of one or more research studies 
in which the institution will be engaged. These regulatory 
flexibilities are intended to reduce administrative burden without 
diminishing human subject protections. For example, two or more 
institutions engaged in the same multi-center research project can 
designate the same IRB (e.g., an IRB operated by one of the 
institutions engaged in the project) on their FWAs to review that 
research project. Similarly, institutions that do not have an internal 
IRB (for example, because they conduct little human subjects research) 
may designate an external IRB on their FWAs to review one or more 
research studies. Another IRB review model permitted under 45 CFR part 
46 is for an institution to designate more than one IRB on its FWA to 
share authority and responsibility for the review of certain research 
studies. For example, the facilitated review model developed by the 
National Cancer Institute utilizes a central IRB, as well as review by 
another IRB--typically an internal IRB operated by the institution 
engaged in the research--that is responsible for considering issues 
related to the local context in which the research will be conducted. 
These regulatory flexibilities under 45 CFR part 46, that permit 
institutions to implement a variety of IRB review arrangements, are 
intended to reduce administrative burdens such as the time associated 
with IRB review for multi-site studies, the time devoted by IRB staff 
and investigators to duplicative IRB review, and the time and personnel 
costs associated with operating an IRB for those institutions that 
choose not to establish an internal IRB.
    Despite the regulatory flexibility to implement a wide range of IRB 
review arrangements, OHRP has become aware that some institutions 
remain reluctant to designate external IRBs on their FWAs and/or rely 
upon cooperative IRB review arrangements.

IV. OHRP Co-Sponsored Meetings on Alternative IRB Models

    OHRP's practice of holding an institution engaged in a human 
subjects research study accountable for noncompliance on the part of an 
external IRB that was designated on the institution's FWA and was 
responsible for reviewing the research was identified as one of the key 
factors influencing institutions' decisions about this issue by 
participants in two meetings on alternative IRB models that OHRP co-
sponsored in November 2005 and November 2006. OHRP co-sponsored these 
meetings along with NIH, AAMC, and ASCO, in response to a suggestion 
made by SACHRP in the fall of 2004 that OHRP further explore issues 
associated with the use of alternatives to local IRBs. Reports 
summarizing the findings of these two meetings can be found at http://www.dhhs.gov/ohrp/sachrp/documents/AltModIRB.pdf and http://www.aamc.org/research/irbreview/irbconf06rpt.pdf. Participants in the 
2005 and 2006 meetings included individuals from a variety of 
perspectives, including IRB chairs, academic investigators, community-
based researchers, attorneys, patients, ethicists, industry officials 
and senior university and medical school research administrators. While 
other factors were also identified as contributing to institutions' 
reluctance to adopt alternatives to the internal IRB review model, it 
is OHRP's understanding from participants in this meeting, as well as 
others in the community, that concerns related to regulatory liability 
are a significant consideration. Namely, one of the main factors 
identified as contributing to institutions' reluctance to rely on an 
external IRB is OHRP's current practice of enforcing compliance with 45 
CFR part 46 through the institutions that were engaged in human 
subjects research, even in circumstances when the regulatory violation 
is directly related to the responsibilities of an external IRB. Given 
this, OHRP believes that expanding its enforcement authority to include 
IRBs and IORGs directly may make institutions more likely to designate 
external IRBs on their FWAs and/or enter into cooperative IRB review 
arrangements.

V. Possible Administrative Actions for Noncompliance by IRBs or IORGs

    If HHS were to implement a regulation that would enable OHRP to 
hold IRBs and IORGs directly accountable for meeting certain regulatory 
requirements of 45 CFR part 46, OHRP envisions that it would generally 
only exercise this regulatory option when the IRB at issue was external 
to the institution engaged in the human subjects research, and was 
designated on the institution's FWA to review the research. In 
circumstances when the IRB at issue was internal to the institution 
engaged in the human subjects research, OHRP expects that it would 
continue to enforce compliance with 45 CFR part 46 through the engaged 
institution.
    However, when the possible regulatory noncompliance at issue was 
the responsibility of an IRB external to the institution engaged in the 
human subjects research, and the external IRB was designated on the 
institution's FWA to review the research, OHRP generally would expect 
to enforce compliance with 45 CFR part 46 directly with the external 
IRB, and not the FWA-holding institution. OHRP contemplates a number of 
administrative actions that HHS could take in response to a finding of 
noncompliance with 45 CFR part 46 by an external IRB designated on an 
institution's FWA. Depending on the nature and scope of the IRB's or 
IORG's noncompliance, OHRP could, for example, require that the IRB or 
IORG implement certain corrective actions, restrict or impose 
conditions on the IRB's registration with OHRP, or suspend the IRB's 
registration with OHRP which would prohibit the IRB from being 
designated on any institution's FWA.

VI. Identifying Responsibilities of the IRB/IORG and FWA-Holding 
Institution

    In considering how HHS would implement a regulation that would 
enable OHRP to hold IRBs and IORGs directly accountable for meeting 
certain regulatory requirements of 45 CFR part 46, OHRP has begun the 
process of identifying which entities might be responsible for 
fulfilling the various regulatory requirements. Some of the regulatory 
requirements seem to fall uniquely to either the IRB/IORG or the FWA-
holding institution, and others seem to be requirements that could be 
carried out by either the IRB/IORG or the FWA-holding institution. OHRP 
envisions that some form of agreement between the IRB/IORG and the FWA-
holding institution would determine which entity would be responsible 
for

[[Page 9581]]

fulfilling the regulatory requirements that could be carried out by 
either the IRB/IORG or the FWA-holding institution. In an attempt to 
facilitate public comment on this request for information regarding IRB 
accountability, OHRP has made a preliminary attempt to group the 
regulatory requirements into the following three categories: (1) 
Responsibilities that may be unique to IRBs and IORGs; (2) 
responsibilities that may be unique to institutions engaged in human 
subjects research; and (3) responsibilities that may be fulfilled by 
either IRBs/IORGs or institutions engaged in human subjects research.
    OHRP considered whether there are any regulatory requirements that 
are inherently shared by both the IRB/IORG and the FWA-holding 
institution, but did not identify any requirements that seemed to fall 
into this category. Section VII of this notice includes a question that 
specifically seeks public comment on this issue.
    The categorization below is in no way intended to be definitive or 
complete, but rather a basis for public comment.

Responsibilities That May Be Unique to IRBs and IORGs

    <bullet> The provisions regarding IRB membership and qualifications 
necessary to promote complete and adequate review of the human subjects 
research conducted by the institution for which the IRB was designated 
on an institution's assurance of compliance with OHRP (Sec.  46.107).
    <bullet> The provision that the IRB follow written procedures in 
the same detail as described in 45 CFR 46.103(b)(4) and to the extent 
required by 45 CFR 46.103(b)(5) (Sec.  108(a)).
    <bullet> The provision that except when an expedited review 
procedure is used (see Sec.  46.110), the IRB review proposed research 
at convened meetings at which 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 (Sec.  46.108(b)).
    <bullet> The provision that an IRB shall review and approve, 
require modifications in (to secure approval), or disapprove all 
research activities covered by 45 CFR part 46, for which the IRB was 
designated on an institution's assurance of compliance with OHRP (Sec.  
46.109(a)).
    <bullet> The provision that an IRB shall require that information 
given to subjects as part of informed consent is in accordance with 
Sec.  46.116. The IRB may require that information, in addition to that 
specifically mentioned in Sec.  46.116, 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 (Sec.  46.109(b)).
    <bullet> The provision that an IRB shall require documentation of 
informed consent or may waive documentation in accordance with Sec.  
46.117 (Sec.  46.109(c)).
    <bullet> The provision that an IRB shall notify investigators and 
the institution in writing of its decision to approve or disapprove the 
proposed research activity, or of modifications required to secure IRB 
approval of the research activity. If the IRB decides to disapprove a 
research activity, it shall include in its written notification a 
statement of the reasons for its decision and give the investigator an 
opportunity to respond in person or in writing (Sec.  46.109(d)).
    <bullet> The provision that an IRB shall conduct continuing review 
of research covered by 45 CFR part 46, at intervals appropriate to the 
degree of risk, but not less than once per year (Sec.  46.109(e)).
    <bullet> The provision related to expedited review procedures for 
certain kinds of research involving no more than minimal risk, and for 
minor changes in approved research (Sec.  46.110).
    <bullet> The provision that identifies the criteria for IRB 
approval of research (Sec.  46.111).
    <bullet> The provisions that permit an IRB to approve a consent 
procedure which does not include, or which alters some or all of the 
elements of informed consent set forth in Sec.  46.116, or waive the 
requirements to obtain informed consent provided the IRB finds and 
documents that specified criteria have been met (Sec.  46.116(c) and 
(d)).
    <bullet> The provisions that require informed consent to be 
documented by use of a written consent form approved by the IRB and 
signed by the subject or the subject's legally authorized 
representative, unless the IRB finds that specified criteria permitting 
the waiver of documentation of informed consent have been met (Sec.  
46.117).

Responsibilities That May Be Unique to Institutions Engaged in Human 
Subjects Research

    <bullet> The provision that institutions engaged in HHS-supported 
human subjects research must submit an FWA to OHRP for approval and 
comply with the requirements imposed as part of the FWA, including 
among other things, the designation of one or more IRBs on the 
institution's FWA that have been registered with OHRP (Sec.  46.103).
    <bullet> The requirement that before implementing a change to an 
IRB-approved research study, an investigator must obtain IRB approval 
for the change, unless the change is designed to eliminate an apparent 
immediate hazard to subjects (Sec.  46.103(b)(4)).
    <bullet> The requirement that an investigator must obtain 
continuing IRB review of ongoing non-exempt human subjects research 
prior to the expiration date of the current IRB approval (Sec.  
46.103(b)(4)).
    <bullet> The requirement for the prompt reporting to the IRB of any 
unanticipated problems involving risks to subjects or others or any 
serious or continuing noncompliance with 45 CFR part 46 or the 
requirements or determinations of the IRB (Sec.  46.103(b)(5)).
    <bullet> The requirement that an investigator must obtain IRB 
review and approval before beginning any non-exempt human subjects 
research (Sec.  46.109(a)).
    <bullet> The provision that the IRB must have authority to approve, 
require modifications in (to secure approval), or disapprove all 
research activities for which the IRB was designated on an 
institution's assurance of compliance with OHRP (Sec.  46.109(a)).
    <bullet> The provision that the IRB must have authority to observe 
or have a third party observe the consent process and the research for 
all research activities for which the IRB was designated on an 
institution's assurance of compliance with OHRP (Sec.  46.109(e)).
    <bullet> The provision that research covered by 45 CFR part 46 that 
has been approved by an IRB may be subject to further appropriate 
review and approval or disapproval by officials of the institution. 
However, these officials may not approve the research if it has not 
been approved by an IRB (Sec.  46.112).
    <bullet> The provision that the IRB must have authority to suspend 
or terminate approval of research that is not being conducted in 
accordance with the IRB's requirements or that has been associated with 
unexpected serious harm to subjects for all research activities for 
which the IRB was designated on an institution's assurance of 
compliance with OHRP (Sec.  46.113).
    <bullet> The requirement that except as provided elsewhere in 45 
CFR part 46 no investigator may involve a human being as a subject in 
research covered by 45 CFR part 46 unless the investigator has obtained 
and documented the legally effective informed consent of the subject or 
the subject's legally authorized representative (Sec.  46.116 and Sec.  
46.117).
    <bullet> The requirement that investigators give a copy of the 
informed consent document to each research subject or

[[Page 9582]]

the subject's legally authorized representative, and keep the signed 
original or a copy of it for their records, unless the IRB finds that 
specified criteria permitting the waiver of documentation of informed 
consent have been met (Sec.  46.117; Sec.  46.115(b)).

Responsibilities That May Be Fulfilled by Either IRBs/IORGs or 
Institutions Engaged in Human Subjects Research

    <bullet> Determining the applicability of the HHS regulations at 45 
CFR part 46 (e.g., the exemptions at 46.101(b)).
    <bullet> Developing written IRB procedures which the IRB will 
follow:
    (1) For conducting its initial and continuing review of research 
and for reporting its findings and actions to the investigator and the 
institution;
    (2) For determining which projects require review more often than 
annually and which projects need verification from sources other than 
the investigators that no material changes have occurred since previous 
IRB review; and
    (3) For ensuring prompt reporting to the IRB of proposed changes in 
a research activity, and for ensuring that such changes in approved 
research, during the period for which IRB approval has already been 
given, may not be initiated without IRB review and approval except when 
necessary to eliminate apparent immediate hazards to the subject (Sec.  
46.103(b)(4)).
    <bullet> Developing written IRB procedures for ensuring the prompt 
reporting to the IRB, appropriate institutional officials, and the 
Department or Agency head of:
    (1) Any unanticipated problems involving risks to subjects or 
others or any serious or continuing noncompliance with 45 CFR part 46 
or the requirements or determinations of the IRB; and
    (2) Any suspension or termination of IRB approval (Sec.  
46.103(b)(5).
    <bullet> Promptly reporting to the appropriate institutional 
officials and the Department or Agency head:
    (1) Any unanticipated problems involving risks to subjects or 
others or any serious or continuing noncompliance with 45 CFR part 46 
or the requirements or determinations of the IRB; and
    (2) Any suspension or termination of IRB approval, including a 
statement of the reasons for the IRB's actions (Sec.  46.103(b)(5); 
Sec.  46.113).
    <bullet> Promptly reporting to the investigator any suspension or 
termination of approval by the IRB, including a statement of the 
reasons for the IRB's actions (Sec.  46.113).
    <bullet> Fulfilling the documentation and recordkeeping 
requirements associated with IRB activities (Sec.  46.115).

VII. Request for Information and Comments

    OHRP is seeking information and comments from the public about 
whether OHRP should pursue an NPRM to enable OHRP to hold IRBs and 
IORGs directly accountable for meeting certain regulatory requirements 
of the HHS regulations for the protection of human subjects at 45 CFR 
part 46. OHRP specifically seeks information and comments on the 
following issues; comments should also include a reference to the 
specific numbered question being addressed:
    1. Is there sufficient need for HHS to pursue a regulatory change 
to enable OHRP to hold IRBs and IORGs directly accountable for meeting 
certain requirements of the HHS regulations at 45 CFR part 46? Please 
explain your response.
    2. Would the proposed regulatory change reduce concerns about 
regulatory liability as a barrier to the use of external IRBs and 
contribute to an increase in collaborative IRB review arrangements?
    3. Are there other approaches and strategies that would decrease 
concern about regulatory liability and increase collaborative IRB 
review arrangements?
    4. If HHS were to issue a regulation that would enable OHRP to hold 
IRBs and IORGs directly accountable for meeting certain requirements of 
the HHS regulations at 45 CFR part 46, would this have the unintended 
effect of making institutions or IORGs less willing to have their IRBs 
designated as external IRBs on other institutions' FWAs? If so, would 
there still be sufficient benefit for HHS to pursue a regulatory change 
to enable OHRP to hold IRBs and IORGs directly accountable for meeting 
certain requirements of the HHS regulations? Are there other possible 
unintended effects of the proposed regulatory change? Please explain 
your responses.
    5. If HHS pursues a regulatory change to enable OHRP to hold IRBs 
and IORGs directly accountable for meeting certain requirements of the 
HHS regulations at 45 CFR part 46, what kinds of administrative actions 
would be appropriate for OHRP to take against IRBs that are found to be 
out of compliance with 45 CFR part 46? For a description of some of the 
corrective actions that OHRP has required when it has been determined 
that an institution was not in compliance with 45 CFR part 46, see 
OHRP's guidance document entitled, ``OHRP's Compliance Oversight 
Procedures for Evaluating Institutions'' at http://www.dhhs.gov/ohrp/compliance/ohrpcomp.pdf.
    6. As described in Section VI of this notice, in order to 
facilitate public comment, OHRP has made a preliminary attempt to group 
some of the regulatory requirements under 45 CFR part 46 into the 
following three categories: (1) Responsibilities that may be unique to 
IRBs and IORGs; (2) responsibilities that may be unique to institutions 
engaged in human subjects research; and (3) responsibilities that may 
be fulfilled by either IRBs/IORGs or institutions engaged in human 
subjects research.
    6a. Are these categories appropriate? If not, what other categories 
should there be?
    6b. Is there a fourth category of responsibilities that are 
inherently shared by both the IRB/IORG and the FWA-holding institution? 
If so, please provide examples of such shared responsibilities.
    6c. Are the regulatory provisions identified under each of the 
categories appropriate? If not, which regulatory provisions should be 
re-categorized, removed, or added?
    6d. For institutions that have relied upon joint IRB review 
arrangements in the past, how have the regulatory requirements been 
divided or shared by the IRB/IORG and the institution engaged in the 
human subjects research? We would welcome examples or descriptions of 
such agreements between IRBs/IORGs and institutions engaged in human 
subjects research that describe their respective responsibilities.
    7. With regard to the responsibilities that may be fulfilled by 
either IRBs or institutions, the IRB Authorization Agreement between an 
external IRB and an FWA-holding institution is often used to clarify 
which entity will be responsible for carrying out these regulatory 
requirements.
    7a. If a regulatory change to 45 CFR part 46 is pursued, should 
OHRP use the IRB Authorization Agreement or other forms of agreement, 
if they exist (e.g., contract or memorandum of understanding) to inform 
its compliance oversight evaluations about which entity should be held 
responsible for fulfilling regulatory requirements that could be met by 
either an external IRB or the FWA-holding institution?
    7b. If a regulatory change to 45 CFR part 46 is pursued, should 
there be new provisions that require specific content for IRB 
Authorization Agreements or for other forms of agreements between 
external IRBs and FWA-holding

[[Page 9583]]

institutions? If so, what types of content should be required?
    7c. If a regulatory change to 45 CFR part 46 is pursued, should the 
regulation describe which regulatory requirements would need to be met 
by external IRBs and which regulatory requirements would need to be met 
by institutions engaged in the research?

    Dated: February 27, 2009.
Jerry Menikoff,
Director, Office for Human Research Protections.
[FR Doc. E9-4628 Filed 3-4-09; 8:45 am]
BILLING CODE 4150-36-P


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