[Federal Register Volume 72, Number 207 (Friday, October 26, 2007)]
[Notices]
[Pages 60848-60851]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-21126]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Protection of Human Subjects: Categories of Research That May Be 
Reviewed by the Institutional Review Board Through an Expedited Review 
Procedure

AGENCY: Department of Health and Human Services, Office of the 
Secretary.

ACTION: Notice.

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SUMMARY: The Office for Human Research Protections (OHRP) is requesting 
written comments on a proposed amendment to item 5 of the categories of 
research that may be reviewed by the institutional review board (IRB) 
through an expedited review procedure, last published in the Federal 
Register on November 9, 1998 (63 FR 60364). On that date, the Office 
for Protection from Research Risks (OPRR), now OHRP, and the Food and 
Drug Administration (FDA) simultaneously published identical lists of 
categories of research activities involving human subjects which may be 
reviewed by the IRB through an expedited review procedure. It has come 
to OHRP's attention that there has been confusion in the research 
community about expedited review category 5. OHRP is proposing to amend 
expedited review category 5 to clarify that the category includes 
research involving materials that were previously collected for either 
nonresearch or research purposes, provided that any materials collected 
for research were not collected for the currently proposed research. 
Expedited review category 5 also includes research involving materials 
that will be collected solely for nonresearch purposes.
    In addition, OHRP is requesting comments on the entire expedited 
review list that was last published in the Federal Register on November 
9, 1998 (63 FR 60364) to determine if other changes are needed.
    As part of its charge to provide expert advice and recommendations 
to the Secretary of Health and Human Services (the Secretary) and the 
Assistant Secretary for Health on issues and topics pertaining to or 
associated with the protection of human research subjects, the 
Secretary's Advisory Committee on Human Research Protections (SACHRP), 
through its Subcommittee on Subpart A, considered whether the current 
expedited review categories should be modified. On March 14, 2007, 
SACHRP submitted recommendations regarding expedited review to the 
Secretary, and on June 18, 2007, the Secretary sent a letter to the 
SACHRP chairperson, stating that HHS would give serious consideration 
to these recommendations. In regard to the current expedited review 
categories, SACHRP recommended that expedited review category 7 should 
be revised as described in Section V below. Therefore, in addition to 
requesting comments on the entire expedited review list that was 
published in the Federal Register on November 9, 1998 (63 FR 60364), 
OHRP is also specifically requesting comments on SACHRP's recommended 
revision of expedited review category 7.
    As required under 21 CFR 56.110(a), FDA also will publish in the 
Federal Register a list of categories of research that may be reviewed 
by the IRB through an expedited review procedure. FDA intends to issue 
the list concurrently with OHRP's issuance of its final notice, and in 
compliance with 21 CFR 10.115 (good guidance practice regulations). 
This approach maintains FDA's practice of moving in tandem on this 
issue with OHRP.

DATES: Submit written or electronic comments by December 26, 2007.

ADDRESSES: Submit written comments to EXPEDITED REVIEW, Office for 
Human Research Protections, The Tower Building, 1101 Wootton Parkway, 
Suite 200, Rockville, MD 20852. Comments also may be sent via e-mail to 
[email protected], or via facsimile at 301-402-2071. Comments 
received within the comment period, including any personal information 
provided, will be made available to the public upon request.

FOR FURTHER INFORMATION CONTACT: Mr. Glen Drew, Office for Human 
Research Protections, The Tower Building, 1101 Wootton Parkway, Suite 
200, Rockville, MD 20852, 1-866-447-4777 or by e-mail to: 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Expedited Review Procedures

    The Department of Health and Human Services (HHS) human subjects 
protection regulations at 45 CFR 46.110 permit expedited review 
procedures for certain kinds of human subjects research that have been 
found by an IRB to involve no more than minimal risk to research 
subjects, or for minor changes in previously IRB-approved research 
during the period (of one year or less) for which approval is 
authorized. An expedited review procedure consists of a review of 
research involving human subjects by the IRB chairperson or by one or 
more experienced reviewers designated by the chairperson from among 
members of the IRB, in

[[Page 60849]]

accordance with the requirements at 45 CFR 46.110.
    The HHS regulations at 45 CFR 46.110 also give the Secretary the 
authority to amend and republish the list of research categories that 
may be reviewed by the IRB through an expedited review procedure, after 
consultation with other departments and agencies. This same section of 
the HHS regulations also requires that an amended expedited review list 
be published by the Secretary in the Federal Register.
    As required by HHS regulations at 45 CFR 46.110, this proposed 
amendment of expedited review category 5 was developed after consulting 
with the other Federal departments and agencies that have promulgated 
the Federal Policy for the Protection of Human Subjects.

II. Background on the Expedited Review List

    The first expedited review list was published by the Secretary in 
1981 (46 FR 8392). On November 10, 1997, OPRR, now OHRP, and FDA 
published identical proposed revisions to the 1981 expedited review 
list (published for OPRR at 62 FR 60607). The category of research in 
question, expedited review category 5, was addressed in the proposed 
categories 4 and 5 in the November 10, 1997 Federal Register Notices 
requesting public comment. In those Notices, proposed categories 4 and 
5 were presented as follows:

    (4) Research involving existing identifiable data, documents, 
records, or biological specimens (including pathological or 
diagnostic specimens) where these materials, in their entirety, have 
been collected prior to the research, for a purpose other than the 
proposed research.
    (5) Research involving solely (a) prospectively collected 
identifiable residual or discarded specimens, or (b) prospectively 
collected identifiable data, documents, or records, where (a) or (b) 
has been generated for nonresearch purposes.

    In addition, a chart included in OPRR's and FDA's November 10, 1997 
Federal Register Notices, comparing the proposed expedited review list 
with the 1981 list, indicated that the proposed category 4 (see above) 
was intended to replace expedited review category 8 on the 1981 list. 
Category 8 on the 1981 list stated, ``the study of existing data, 
documents, records, pathological specimens, or diagnostic specimens.''
    The comments received on OPRR's and FDA's November 10, 1997 Federal 
Register Notices overwhelmingly supported the proposed revision to the 
expedited review list. With minor modifications to the 1997 proposed 
expedited review list, on November 9, 1998, OPRR and FDA simultaneously 
published identical revised lists of categories of research activities 
that may be reviewed by the IRB through the expedited review procedure 
(published for OPRR at 63 FR 60364, and for FDA at 63 FR 60353). In 
regard to expedited review category 5, the OPRR and FDA November 9, 
1998 Federal Register Notices described this category of research as:

    (5) Research involving materials (data, documents, records, or 
specimens) that have been collected or will be collected solely for 
nonresearch purposes (such as medical treatment or diagnosis). 
(Note: Some research in this category may be exempt from the HHS 
regulations for the protection of human subjects. 45 CFR 
46.101(b)(4). This listing refers only to research that is not 
exempt.)

    The preamble of the OPRR November 9, 1998 Federal Register Notice 
explained that:

    Categories four (4) and five (5) on the proposed list have been 
combined into one new category five (5) on the 1998 list. This new 
section is added in response to comments that raised questions about 
the relationship of proposed categories four (4) and five (5) to 
exempt research and about separating out existing and prospectively 
collected materials. The term ``nonresearch purposes'' was 
maintained in new category five (5) to describe the origins of the 
research material * * *

    Similarly, the FDA November 9, 1998 Federal Register Notice 
explained that:

    Categories four and five on the proposed list have been combined 
into one new category, category five, addressing research involving 
materials collected or which will be collected solely for 
nonresearch purposes. This new category five was formed in response 
to comments that raised questions about why the two categories 
separated out existing and prospectively collected materials. The 
term ``nonresearch purposes'' was maintained in new category five to 
describe the origins of the research materials.

III. Clarification on the Scope of Expedited Review Category Five (5) 
Needed

    The description of expedited review category 5 and the preamble 
language as published in the November 9, 1998 OPRR and FDA Federal 
Register Notices has caused confusion in the research community about 
whether this expedited review category includes research involving 
materials that were originally collected for either nonresearch or 
research purposes, or is limited to research involving materials that 
were originally collected solely for nonresearch purposes.
    As evidence of this confusion, in their 1999 report, Research 
Involving Human Biological Materials: Ethical Issues and Policy 
Guidance, the National Bioethics Advisory Commission (NBAC) stated:

    NBAC finds that there is no need to distinguish between 
collections originally created for clinical purposes and those 
created for research purposes. In both cases, research on the 
collected materials should be eligible for expedited review if the 
research presents no more than a minimal risk to the study subjects.

    As a result of this finding, NBAC recommended that ``OPRR should 
revise its guidance to make clear that all minimal-risk research 
involving human biological materials--regardless of how they were 
collected--should be eligible for expedited IRB review.'' In response 
to NBAC's 1999 report, HHS convened a multi-agency Working Group to 
analyze the appropriateness, feasibility, and practical implications of 
implementing NBAC's recommendations and to develop a set of proposed 
HHS activities to enhance the protection of human subjects in research 
involving human biological materials. In regard to the NBAC 
recommendation above, the HHS Working Group stated:

    The Working Group concurs with Recommendation 2 and agrees with 
NBAC that, for purposes of determining eligibility for expedited IRB 
review, it is not necessary to draw a distinction between samples 
originally collected for clinical purposes and those obtained for 
research purposes. The Working Group also agrees with NBAC's 
observation that current guidance regarding the types of research 
that IRBs may review through expedited procedures (63 FR 60364 [HHS] 
and 60353 [FDA], November 9, 1998) appears to exclude research 
utilizing existing specimens previously collected for research 
purposes. It is the understanding of the Working Group that this 
apparent exclusion is not intentional but rather resulted from a 
copy editing oversight * * *

IV. OHRP Assessment

    After reviewing OPRR's and FDA's 1997 and 1998 Federal Register 
notices concerning revisions to the 1981 expedited review list, NBAC's 
recommendation, and the HHS Working Group's response, OHRP has 
concluded that expedited review category 5 was intended to, and should, 
include research involving existing information or specimens that were 
previously collected for nonresearch purposes, as well as research 
involving existing information or specimens that were previously 
collected for research purposes--provided they were not collected for 
the currently proposed research.
    OHRP notes that neither OPRR's nor FDA's November 10, 1997 Federal 
Register Notice indicated that the proposed expedited review category 4

[[Page 60850]]

was intended to narrow category 8 on the 1981 list to exclude existing 
specimens that were collected for research purposes, provided the 
materials were collected for a research purpose other than the proposed 
research. Because proposed category 4 would have applied to research 
involving existing identifiable information or specimens that had been 
previously collected for either research or nonresearch purposes, 
provided they were not collected for the currently proposed research, 
OHRP has concluded that the term ``nonresearch purposes'' was retained 
in the final version of category 5 to describe the origins of the 
prospectively collected material only, not the origins of the 
previously collected material. However, this intent was not made clear 
in either OPRR's or FDA's November 9, 1998 Federal Register Notice.

V. OHRP Request for Comments

    For the reasons described in Section IV, OHRP is proposing to 
revise expedited review category 5 as set forth below.
    Remove (5) in its entirety, and add, in its place:

    (5) Research involving materials (data, documents, records, or 
specimens) that
    (a) have previously been collected for nonresearch purposes;
    (b) have previously been collected for research purposes, provided 
the materials were not collected for the currently proposed research; 
or
    (c) will be collected solely for nonresearch purposes.

     Note: Some research under section (a) or (b) of this category 
may be exempt from the HHS regulations for the protection of human 
subjects. 45 CFR 46.101(b)(4). This listing refers only to research 
that is not exempt.

    OHRP is also requesting comments on the entire expedited review 
list that was last published in the Federal Register on November 9, 
1998 (63 FR 60364) to determine if other changes are needed. The 
following is the current expedited review list, as published in the 
Federal Register on November 9, 1998:

    (1) Clinical studies of drugs and medical devices only when 
condition (a) or (b) is met.
    (a) Research on drugs for which an investigational new drug 
application (21 CFR Part 312) is not required. (Note: Research on 
marketed drugs that significantly increases the risks or decreases 
the acceptability of the risks associated with the use of the 
product is not eligible for expedited review.)
    (b) Research on medical devices for which (i) an investigational 
device exemption application (21 CFR Part 812) is not required; or 
(ii) the medical device is cleared/approved for marketing and the 
medical device is being used in accordance with its cleared/approved 
labeling.
    (2) Collection of blood samples by finger stick, heel stick, ear 
stick, or venipuncture as follows:
    (a) from healthy, nonpregnant adults who weigh at least 110 
pounds. For these subjects, the amounts drawn may not exceed 550 ml 
in an 8 week period and collection may not occur more frequently 
than 2 times per week; or
    (b) from other adults and children,\2\ considering the age, 
weight, and health of the subjects, the collection procedure, the 
amount of blood to be collected, and the frequency with which it 
will be collected. For these subjects, the amount drawn may not 
exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and 
collection may not occur more frequently than 2 times per week.
    (3) Prospective collection of biological specimens for research 
purposes by noninvasive means.
    Examples: (a) Hair and nail clippings in a nondisfiguring 
manner; (b) deciduous teeth at time of exfoliation or if routine 
patient care indicates a need for extraction; (c) permanent teeth if 
routine patient care indicates a need for extraction; (d) excreta 
and external secretions (including sweat); (e) uncannulated saliva 
collected either in an unstimulated fashion or stimulated by chewing 
gumbase or wax or by applying a dilute citric solution to the 
tongue; (f) placenta removed at delivery; (g) amniotic fluid 
obtained at the time of rupture of the membrane prior to or during 
labor; (h) supra- and subgingival dental plaque and calculus, 
provided the collection procedure is not more invasive than routine 
prophylactic scaling of the teeth and the process is accomplished in 
accordance with accepted prophylactic techniques; (i) mucosal and 
skin cells collected by buccal scraping or swab, skin swab, or mouth 
washings; (j) sputum collected after saline mist nebulization.
    (4) Collection of data through noninvasive procedures (not 
involving general anesthesia or sedation) routinely employed in 
clinical practice, excluding procedures involving x-rays or 
microwaves. Where medical devices are employed, they must be 
cleared/approved for marketing. (Studies intended to evaluate the 
safety and effectiveness of the medical device are not generally 
eligible for expedited review, including studies of cleared medical 
devices for new indications.)
    Examples: (a) Physical sensors that are applied either to the 
surface of the body or at a distance and do not involve input of 
significant amounts of energy into the subject or an invasion of the 
subject's privacy; (b) weighing or testing sensory acuity; (c) 
magnetic resonance imaging; (d) electrocardiography, 
electroencephalography, thermography, detection of naturally 
occurring radioactivity, electroretinography, ultrasound, diagnostic 
infrared imaging, doppler blood flow, and echocardiography; (e) 
moderate exercise, muscular strength testing, body composition 
assessment, and flexibility testing where appropriate given the age, 
weight, and health of the individual.
    (5) Research involving materials (data, documents, records, or 
specimens) that have been collected, or will be collected solely for 
nonresearch purposes (such as medical treatment or diagnosis). 
(Note: Some research in this category may be exempt from the HHS 
regulations for the protection of human subjects. 45 CFR 
46.101(b)(4). This listing refers only to research that is not 
exempt.)
    (6) Collection of data from voice, video, digital, or image 
recordings made for research purposes.
    (7) Research on individual or group characteristics or behavior 
(including, but not limited to, research on perception, cognition, 
motivation, identity, language, communication, cultural beliefs or 
practices, and social behavior) or research employing survey, 
interview, oral history, focus group, program evaluation, human 
factors evaluation, or quality assurance methodologies. (Note: Some 
research in this category may be exempt from the HHS regulations for 
the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). 
This listing refers only to research that is not exempt.)
    (8) Continuing review of research previously approved by the 
convened IRB as follows:
    (a) Where (i) the research is permanently closed to the 
enrollment of new subjects; (ii) all subjects have completed all 
research-related interventions; and (iii) the research remains 
active only for long-term follow-up of subjects; or
    (b) where no subjects have been enrolled and no additional risks 
have been identified; or
    (c) where the remaining research activities are limited to data 
analysis.
    (9) Continuing review of research, not conducted under an 
investigational new drug application or investigational device 
exemption where categories two (2) through eight (8) do not apply 
but the IRB has determined and documented at a convened meeting that 
the research involves no greater than minimal risk and no additional 
risks have been identified.

    In addition to requesting comments on all of the expedited review 
categories listed above, OHRP specifically requests comments on a 
recommendation by SACHRP to revise expedited review category 7 as 
follows:

    Research (a) on individual or group characteristics or behavior 
(including, but not limited to, research on perception, cognition, 
motivation, affective states, interpersonal relationships, identity, 
language, communication, cultural beliefs or practices, and social 
behavior); or (b) employing methods commonly used in social, 
behavioral, epidemiologic, health services and educational research 
(including, but not limited to, survey, interview, oral history, 
participant observation, ethnographic, focus group, program 
evaluation, human factors evaluation, or quality assurance methods). 
(Note: Some research in this category may be exempt from the HHS 
regulations for the protection of human subjects. 45 CFR 
46.101(b)(2) and (b)(3). This listing refers only to research that 
is not exempt.)


[[Page 60851]]


    Dated: October 22, 2007.
Ivor A. Pritchard,
Acting Director, Office for Human Research Protections.
 [FR Doc. E7-21126 Filed 10-25-07; 8:45 am]
BILLING CODE 4150-36-P