9578 Federal Register / Vol. 74, No. 42 / Thursday, March 5, 2009 / Proposed Rules 

public hearing.’’ is corrected to read 

‘‘Notice of proposed rulemaking by 

cross-reference to temporary regulations 

and notice of public hearing.’’. 

2. On page 236, column 3, in the 

preamble, under the paragraph heading 

‘‘Special Analyses’’, last line of the 

column, the language ‘‘sharing 

agreements. Few small entities’’ is 

corrected to read ‘‘sharing arrangements. 

Few small entities’’. 

3. On page 237, column 1, in the 

preamble, under the paragraph heading 

‘‘Special Analyses’’, first paragraph of 

the column, line 2, the language 

‘‘agreements, as defined by these’’ is 

corrected to read ‘‘arrangements, as 

defined by these’’. 

4. On page 237, column 1, in the 

preamble, under the paragraph heading 

‘‘Comments and Public Hearing’’, third 

paragraph, line 1, the language ‘‘The 

rules of 26 CFR 601.601(a)(93)’’ is 

corrected to read ‘‘The rules of 26 CFR 

601.601(a)(3)’’. 

§ 1.482–2 [Corrected] 

5. On page 237, column 3, § 1.482– 

2(f)(2), the language ‘‘Election to apply 

paragraph (b) of this section to earlier 

taxable years.’’ is corrected to read 

‘‘Election to apply paragraph (b) to 

earlier taxable years.’’. 

LaNita Van Dyke, 

Chief, Publications and Regulations Branch, 

Legal Processing Division, Associate Chief 

Counsel (Procedure and Administration). 

[FR Doc. E9–4687 Filed 3–4–09; 8:45 am] 

BILLING CODE 4830–01–P 

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. 

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 multisite 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: 

• E-mail: IRBaccountability@hhs.gov. 

Include ‘‘IRB Accountability RFI’’ in the 

subject line. 

• Fax: 301–402–2071. 

• 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 

julie.kaneshiro@hhs.gov. 

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 nonexempt 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 nonexempt 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 


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-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: 

• 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 

• 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 


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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 nontraditional 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 multisite 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 cosponsored 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, communitybased 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 FWAholding institution would determine 

which entity would be responsible for 


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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 

• 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 (§ 46.107). 

• 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) (§ 108(a)). 

• The provision that except when an 

expedited review procedure is used (see 

§ 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 

(§ 46.108(b)). 

• 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 (§ 46.109(a)). 

• The provision that an IRB shall 

require that information given to 

subjects as part of informed consent is 

in accordance with § 46.116. The IRB 

may require that information, in 

addition to that specifically mentioned 

in § 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 (§ 46.109(b)). 

• The provision that an IRB shall 

require documentation of informed 

consent or may waive documentation in 

accordance with § 46.117 (§ 46.109(c)). 

• 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 (§ 46.109(d)). 

• 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 (§ 46.109(e)). 

• 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 (§ 46.110). 

• The provision that identifies the 

criteria for IRB approval of research 

(§ 46.111). 

• 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 § 46.116, or waive 

the requirements to obtain informed 

consent provided the IRB finds and 

documents that specified criteria have 

been met (§ 46.116(c) and (d)). 

• 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 (§ 46.117). 

Responsibilities That May Be Unique to 

Institutions Engaged in Human Subjects 

Research 

• 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 (§ 46.103). 

• The requirement that before 

implementing a change to an IRBapproved research study, an investigator 

must obtain IRB approval for the 

change, unless the change is designed to 

eliminate an apparent immediate hazard 

to subjects (§ 46.103(b)(4)). 

• 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 

(§ 46.103(b)(4)). 

• 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 

(§ 46.103(b)(5)). 

• The requirement that an 

investigator must obtain IRB review and 

approval before beginning any nonexempt human subjects research 

(§ 46.109(a)). 

• 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 (§ 46.109(a)). 

• 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 (§ 46.109(e)). 

• 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 (§ 46.112). 

• 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 (§ 46.113). 

• 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 (§ 46.116 and 

§ 46.117). 

• The requirement that investigators 

give a copy of the informed consent 

document to each research subject or 


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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 (§ 46.117; § 46.115(b)). 

Responsibilities That May Be Fulfilled 

by Either IRBs/IORGs or Institutions 

Engaged in Human Subjects Research 

• Determining the applicability of the 

HHS regulations at 45 CFR part 46 (e.g., 

the exemptions at 46.101(b)). 

• 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 (§ 46.103(b)(4)). 

• 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 (§ 46.103(b)(5). 

• 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 

(§ 46.103(b)(5); § 46.113). 

• 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 (§ 46.113). 

• Fulfilling the documentation and 

recordkeeping requirements associated 

with IRB activities (§ 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 


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Federal Register / Vol. 74, No. 42 / Thursday, March 5, 2009 / Proposed Rules 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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