The ANPRM also considered whether to include on the list of exempt
studies certain types of social and behavioral research conducted with
competent adults that would involve specified types of benign
interventions commonly used in social and behavioral research, that are
known to involve virtually no risk to subjects, and for which prior
review does little to increase protections to subjects. These would be
methodologies that are familiar to people in everyday life and in which
verbal or similar responses would constitute the research data being
collected. For example, an investigator might ask subjects to watch a
video, read a paragraph, or solve puzzles, and then ask them some
questions to elicit word associations or time performance of
activities. The specific methodologies might be spelled out in
regulations, or they might be promulgated via a periodic mechanism to
announce and update lists similar to the list that is published for
activities that may be reviewed by an IRB using the expedited review
procedures.\103\
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    \103\ 63 FR 60364 (Nov 9, 1998). Also available at, http://www.hhs.gov/ohrp/policy/expedited98.html.
---------------------------------------------------------------------------

    A majority of commenters supported the ANPRM discussion on
expanding current exemption category 2 (current Rule at Sec.
__.101(b)(2)) by eliminating the limitations related to the recording
of identifiable information and the harm that could result if a
subject's responses were disclosed. However, many commenters were
opposed to the requirement that subjects be ``competent adults'' in
order for the expanded exemption to apply, asking whether tests of
competency would be required for such research to proceed.
    Many commenters also supported adding another exemption category of
research for certain types of social and behavioral activities,
conducted with competent adults, that would involve specified types of
benign interventions beyond educational tests, surveys, focus groups,
interviews, and similar procedures that are commonly used in social and
behavioral research, that are known to involve virtually no risk to
subjects, and for which IRB review does little to increase protections
for subjects.
    The ANPRM asked questions about whether the current limitations
specified in exempt category 4 (research involving the use of existing
information or biospecimens, Sec.  __.101(b)(4) in the current Rule)
should be eliminated. Specifically, the ANPRM suggested that the
category would be revised to eliminate the word ``existing.'' With this
elimination, the exemption would be broadened to cover the use of
information or biospecimens that were or will be collected for purposes
other than the suggested research, rather than requiring that all of
the information or biospecimens already exist at the time the study is
suggested for exemption.
    The ANPRM also discussed whether research involving only the use of
data or biospecimens collected for other purposes, even if the
investigator intends to retain identifiers, should come within a new
exemption category; studies that include a plan to provide individual
research results to subjects would not qualify for this proposed
exemption. In addition, the ANPRM asked whether certain flexible
consent requirements could be imposed on some of these studies that
would permit the use of a broad consent for future use, with a
requirement that a subject's specific consent would be required before
their biospecimens could be used for special categories of research.
    Many of the comments supported the discussion in the ANPRM of
eliminating the requirement that the information or biospecimens be
``existing'' at the time the study was suggested for exemption.
However, a majority strongly disagreed that biospecimens should be
considered or treated as though they were inherently identifiable. A
majority also opposed the suggestion that there be consent requirements
for the research use of nonidentifiable biospecimens collected for
purposes other than the current research study.
    Some commenters also favored requiring IRB review and approval for
the use of identifiable private information and identifiable
biospecimens, rather than permitting the use of a broad consent for
future use to satisfy the regulatory requirement for consent. These
commenters indicated that IRB review of specific research studies, and
the IRB's consideration of whether a study specific informed consent
should be required or whether informed consent could be waived, was
more protective of human subjects than the ANPRM recommendation of
permitting use of a broad consent for future use.
    The ANPRM asked several questions about the interpretation and
applicability of current exemption category 5 (current Rule at

Sec.  __.101(b)(5)), including the scope of the current interpretation
of the category 5 exemption. The ANPRM also asked if the current
category 5 guidance entitled, ``OPRR Guidance on 45 CFR 46.101(b)(5)''
\104\ should be revised, or if additional guidance on the
interpretation of exemption category 5 is needed.
---------------------------------------------------------------------------

    \104\ See 48 FR 9266-9270 (Mar 4, 1983). (OPRR Guidance on 45
CFR 46.101(b)(5), Exemption for Research and Demonstration Projects
on Public Benefit and Service Programs, http://www.hhs.gov/ohrp/policy/exmpt-pb.html).
---------------------------------------------------------------------------

    There were few responses to these questions. However, those that
did comment noted that this category is often misunderstood by IRBs
and, at best, would benefit from clearer guidance. Commenters said that
examples would help investigators and IRBs understand when research
activities included in demonstration projects constitute human subjects
research subject to the Common Rule. Commenters noted that many
activities in demonstration projects do not contribute to generalizable
knowledge as they produce results that are relevant only to the program
being assessed; as such, many of these activities do not meet the
Common Rule's regulatory definition of ``research'' and thus fall
outside of the rule. Other commenters said that some activities in this
category are mandated or required by law or regulation and should not
be considered to be under the purview of the Common Rule. It was noted
that the critical issue in these studies should be protecting privacy
and as long as measures are in place to do so, additional protections
are not required.
3. Expedited Review
    The ANPRM discussed and sought comment on three possible changes to
the review of research through expedited review: (1) Revising the
definition of minimal risk, which is one of the criteria for
determining whether a study is eligible for expedited review; (2)
changing the default position so that research on the expedited review
list could generally be presumed to involve minimal risk; (3) revising
the criteria for approval of research studies under expedited review;
and (4) allowing appropriately trained individuals who are not IRB
members to conduct expedited reviews.
    Definition of Minimal Risk: The ANPRM asked for public comment on
whether the current regulatory definition of minimal risk \105\ was
appropriate. The definition of minimal risk has relevance to
determining whether a protocol is eligible for expedited review. Public
comments expressed both a desire to retain the current definition
(slightly less than half) and a desire for changing it (slightly more
than half). There were few common themes in the suggested changes to
the language other than seeking clarification on what baselines an IRB
should consider in determining the meaning of ``daily life'' and
``routine physical or psychological examinations.'' Several commenters
acknowledged the difficulty of arriving at a concise definition for all
circumstances. Those opposed to changing the definition said that IRBs
generally understand how to interpret the language and that difficult
or challenging application of the definition will persist regardless of
the definition for those areas of research where risks are difficult to
assess. Commenters recognized that the risks encountered in daily life
can vary greatly depending on many factors, for example, where people
live, what kind of work they are involved in, what their social and
economic environment is, and their baseline health status. Thus, IRBs
need to consider all of these issues in making a determination about
the level of risk.
---------------------------------------------------------------------------

    \105\ The current rule states that minimal risk means that the
probability and magnitude of harm or discomfort anticipated in the
research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine
physical or psychological examinations or tests. (45 CFR 46.102(i)).
---------------------------------------------------------------------------

    Eligibility for Expedited Review: The ANPRM suggested updating the
current list of research activities eligible for expedited review; this
list was last updated in 1998. It also considered mandating that a
federal panel periodically (such as every year or every two years)
review and update the list, based on a systematic, empirical assessment
of the levels of risk. This would provide greater clarity about what
would be considered to constitute minimal risk, and create a process
that allows for routinely reassessing and updating the list of research
activities that would qualify as minimal risk. The ANPRM asked for
public comments on categories of research that should be considered for
addition to the current list.
    Several commenters provided suggestions for additions to the list
of research activities eligible for expedited review. Others encouraged
OHRP to consider developing principles for expedited review, rather
than creating a revised list of research activities. Commenters
suggested a more timely and consistent review of the list because of
the rapidly changing state of science and technology.
    The ANPRM also discussed the potential adoption of a default
presumption in the rule that a study that includes only activities on
the expedited review list is a minimal risk study and should receive
expedited review. A reviewer would have the option of determining that
the study should be reviewed by a convened IRB when that conclusion is
supported by the specific circumstances of the study. The ANPRM also
asked for comments on whether IRBs should be required to report
instances when they overrode the default presumption that research
appearing on the posted list did not warrant review by a convened IRB.
    Commenters overwhelmingly welcomed the clarification that
categories of research found on the published list should be presumed
to be minimal risk. However, commenters were largely opposed to
requiring IRBs to report instances when they conducted a review by the
convened membership (versus an expedited review) for studies appearing
on the list. They were opposed because of the additional administrative
burden and also because they felt such a requirement would undermine
the purview of local review and open IRBs up to second-guessing by
OHRP.
    Criteria for Approval under Expedited Review: The ANPRM asked
whether all of the Sec.  __.111 criteria should still be required for
approval of studies that qualify for expedited review, and if not,
which ones should not be required. Currently, before an IRB may approve
a research study, including research that is being reviewed under an
expedited procedure, the IRB must find that the criteria at Sec.
__.111 have been met.
    With regard to revising the criteria used for expedited review,
comments were mixed. Nearly half of those commenting expressed concerns
about establishing two sets of ethical standards for IRB review--one
for convened review and one for expedited review. They asserted ethical
and administrative concerns about operating under two sets of
conditions and principles--that is, expedited review should not be
viewed as less stringent than review conducted by a convened IRB.
    Those commenters in favor of retaining the current criteria wrote
that a double standard could result in arbitrary IRB decision making.
In addition, many wrote that the current criteria are well understood
by IRB members and the tendency to review a protocol through a convened
IRB when expedited review would be permissible is more a function of
institutional

concerns about liability than the regulatory requirements. They cited
the regulatory language at Sec.  __.111, which frequently contains the
phrase ``wgeb appropriate,'' so that the reviewer(s) can exercise
discretion in whether all of the criteria need to be applied.
    Those in favor of revising the elements most often cited the
irrelevance of some of the criteria for minimal risk research, such as
the need to ensure that risks to subjects are reasonable in relation to
anticipated benefits (Sec.  __.111)(a)(2)). They stated that in the
case of minimal risk research, the need to balance risks with benefits
is not pertinent. Some commenters asked OHRP to develop guidance for
the expedited reviewer in interpreting the most relevant criteria
during expedited review.
    Several commenters noted that if the revised regulations remove the
requirement for continuing review of studies initially reviewed through
expedited review it would alleviate administrative burden; thus more
extreme measures such as revising the review criteria would be less
compelling.
    Who May Conduct Expedited Reviews: The ANPRM asked for public
comment on the advantages and disadvantages of requiring that expedited
review be conducted by an IRB member versus an appropriately trained
individual, such as the manager of the IRB office, who need not be a
member of the IRB.
    With regard to allowing a non-IRB member to conduct expedited
review, comments were divided nearly evenly between those who opposed
such a change and those who supported it. Those who opposed it cited
the need for continuity and consistency across IRBs, as well as
expressing concerns about accountability and liability. Those in favor
of such a revision cited the expertise of IRB staff members and their
ability to review many expedited studies at the same level as a member
of the IRB.
4. Streamlining IRB Review
    Cooperative Research: The ANPRM sought public comment on the
feasibility, advantages, and disadvantages of mandating that all
domestic (U.S.) sites in a study involving more than one institution
rely on a single IRB for that study. This would apply regardless of
whether the study underwent convened review or expedited review.
Further, it would only affect which IRB would be designated as the
reviewing IRB for institutional compliance with the IRB review
requirements of the Common Rule. It would not relieve any site of its
other obligations under the regulations to protect human subjects. Nor
would it prohibit institutions from choosing, for their own purposes,
to conduct additional internal ethics reviews, though such reviews
would no longer have any regulatory status in terms of compliance with
the Common Rule.
    To address institutions' concerns about OHRP's practice of
enforcing compliance with the Common Rule through the institutions that
are engaged in human subjects research, the ANRPM also suggested that
appropriate accompanying changes could be made in enforcement
procedures to hold external IRBs directly accountable for compliance
with certain regulatory requirements.\106\ This change was discussed
only for U.S. sites in multi-institutional studies. The ANPRM suggested
that, in most cases, independent local IRB reviews of international
sites are appropriate because it might be difficult for an IRB in the
U.S. to adequately evaluate local conditions in a foreign country that
could play an important role in the ethical evaluation of the study.
---------------------------------------------------------------------------

    \106\ 74 FR 9578 (Mar. 5, 2009). Also available at http://www.hhs.gov/ohrp/newsroom/rfc/com030509.html.
---------------------------------------------------------------------------

    This issue attracted a large number of comments, and revealed
nearly evenly divided perspectives. Researchers and disease advocacy
groups tended to favor the single IRB review requirement. IRB and
institutional representatives tended to be opposed to the possible
requirement, though many indicated single IRB review should be
encouraged. Support was especially strong for single IRB review for
cooperative clinical trials for which the evaluation of a study's
social value, scientific validity, and risks and benefits, and the
adequacy of the informed consent form and process generally do not
require the unique perspective of a local IRB. Moreover, depending on
the nature of the study, FDA may not permit differences in protocols
across sites, which further bolstered commenters' views that the
requirements be harmonized across the Common Rule and FDA requirements.
Commenters reported incidences of IRBs continuously second-guessing
each other, which delayed studies to the point that subject recruitment
opportunities were foregone or lost. This problem seemed especially
critical in studies of rare diseases and cancers, which nearly always
involve multiple research sites.
    Support for the use of a single IRB, however, was not restricted to
clinical trials. Several commenters cited long delays and burdensome
requirements resulting from multiple reviews of studies in the
behavioral and social sciences. In addition to the view that these
administrative requirements do not enhance protections, supporters of a
single IRB review of cooperative studies cited the frequent need for
maintaining consistency across sites, which can be degraded by multiple
reviews.
    Despite support for the ANPRM suggestion, several commenters
expressed concern about making such a provision mandatory, stating that
the current regulations at Sec.  __.114 currently permit the use of
joint review arrangements for cooperative research. They noted that
although this option exists, institutions might be hesitant to use it
because of liability concerns and the unwillingness of institutions or
IRBs to rely on the judgment of other institutions or IRBs. However,
several commenters expressed concern about signaling the acceptability
of a single IRB for review while allowing institutions to continue to
conduct their own ethics review, fearing that such a policy would not
correct the current situation, which tends to favor multiple reviews.
Thus, they commented that mandating a single IRB might be the only way
to achieve the goals of streamlining review while ensuring protections.
    Another issue raised was the need to set clearer expectations of
the responsibilities of local IRBs that are not designated as the
central IRB. A number of commenters supporting the requirement for a
central IRB also requested that OHRP issue guidance on how to select
the IRB, responsibilities of all parties, and clarifying compliance and
enforcement policies. Several commenters also requested that OHRP
develop a template for reliance agreements to replace inter-
institutional agreements currently in use.
    Those who expressed concern about the use of a single IRB said some
studies, especially in the behavioral and social sciences, might
involve significant contextual issues reflecting community norms,
standards, and practices, or local culture and customs. Use of a
distant IRB might not consider and best protect subjects based on
community norms. Others noted that such concerns can be addressed by
investigators or IRBs submitting ``points to consider'' regarding
significant contextual or cultural considerations of relevance to their
site.
    A primary issue posed by those opposed to mandating use of a single
IRB in cooperative studies focused on potential loss of accountability
and increased liability for the institutions

where the research is conducted but where the reviewing IRB is not
located.
    Streamlining Documentation Requirements for Expedited Studies:
Under the current Common Rule, investigators typically must submit the
same documents including a detailed protocol, informed consent forms,
and any other supporting documents, regardless of whether the study
will be reviewed by a convened IRB or be approved by the expedited
review process. The ANPRM suggested that although it is important to
document why research qualifies for expedited review, it is unclear
whether the time and effort expended in such preparation activities
result in increased benefit in terms of protecting subjects.
    The ANPRM further suggested that standard templates for protocols
and consent forms and sample versions of those documents that are
specifically designed for use in the most common types of studies might
facilitate expedited review. Such forms would need to be carefully
designed to eliminate those elements that are of relevance only in
studies that pose greater than minimal risks and to substantially
reduce the current burden of researchers involved in producing these
documents and of the IRB members who review them. The ANPRM asked
whether there were specific changes that could be made to reduce the
burden imposed on investigators and their staffs in terms of meeting
the requirements to submit documents to an IRB, without decreasing
protections to subjects.
    There were few comments on streamlining the document submission
requirements for expedited review, and there was no consensus among
those who did comment about how to achieve that goal.
    Continuing Review: The ANPRM asked for public comments on
eliminating continuing review for all minimal risk studies that undergo
expedited review, unless the reviewer explicitly justifies why
continuing review would enhance protection of research subjects.
    Additionally, the ANPRM suggested that, for studies initially
reviewed by a convened IRB, continuing review would not be required
after the study reaches the stage where procedures are limited to
either: (1) Analyzing data (even if it is identifiable), or (2)
accessing follow-up clinical data from procedures that subjects would
undergo as part of standard care for their medical condition or disease
(such as periodic CT scans to monitor whether the subjects' cancers
have recurred or progressed) unless specifically mandated by the IRB,.
This would be a change from the current Rules, which require at least
expedited IRB review of the activities described in (1) and (2) above.
The requirement that research involving greater than minimal risk be
reviewed by a convened IRB would not be changed from the current
system.
    By eliminating the requirement for continuing review of these
activities, the ANPRM suggested that this change would allow for more
effective use of IRBs' time by enabling the IRB to focus on reviewing
information that is necessary to ensure protection of research
subjects. Requiring annual continuing review of research studies
involving only activities that are already well-documented to generally
involve no more than minimal risk may provide little if any added
protection to subjects, and it may be preferable for IRB resources to
be devoted to research that poses greater than minimal risk.
    The ANPRM asked for public comment on whether it would be
appropriate to require IRBs to submit periodic reports to OHRP in the
instances in which they choose to override the default policy of no
continuing review required for the situations described above. The
information, if collected by OHRP, might be useful in developing future
guidance or revising the categories of research eligible for expedited
review.
    A large majority of public comments were in favor of the suggested
revisions. Many were comfortable with continuing to allow IRBs or
reviewers the discretion to require continuing review in certain
circumstances, citing the historical position of OHRP in considering
the regulations as the floor, rather than the ceiling, for protecting
the subjects of research. Those who were opposed to the revisions cited
concerns about institutional liability, the possibility for increased
noncompliance among investigators no longer required to ``check in,''
and possible breakdowns in lines of communications between
investigators and IRBs. Others expressed concerns about how an IRB will
know that a study has ended and suggested that investigators be
required to file a notice of closure of a study.
    Note that the November 10, 2010, document entitled, ``Guidance on
IRB Continuing Review of Research'' states:

    OHRP is aware that many IRBs require investigators to submit
final closeout reports when a research study is completed or no
longer involves human subjects. Since the HHS regulations at 45 CFR
part 46 do not require submission of such reports, institutions are
free to decide whether and when such reports are required and what
their content should include.\107\
---------------------------------------------------------------------------

    \107\ Office for Human Research Protections. (2010, November
10). Identifying the Point When Continuing Review is no Longer
Necessary. Retrieved from Guidance on IRB Continuing Review of
Research: http://www.hhs.gov/ohrp/policy/continuingreview2010.html#section-k.

    Commenters overwhelmingly opposed requiring IRBs to periodically
report on the instances when they (or a reviewer) elect to override the
default position of no continuing review required. The reasons for
opposition included: (1) Additional administrative burden that would
negate the reduced burden gained; (2) the possibility that requiring
such reporting would discourage IRBs/reviewers from making an override
decision; and (3) concerns that such reports would lead to OHRP second-
guessing IRB decisions and imposing compliance oversight in an extra-
regulatory decision. Several commenters suggested that OHRP could use
other means than this requirement for developing guidance and improving
educational efforts regarding expedited and continuing review.
5. Improving Harmonization
    The ANPRM did not suggest any specific approaches to harmonization
but asked for public comment on a set of questions focused on: (1) The
extent to which differences in guidance on research protections from
different agencies strengthen or weaken protections for human subjects;
(2) the extent to which differences in guidance on research protections
from different agencies facilitate or inhibit the conduct of research
domestically and internationally; and (3) the desirability of all
Common Rule agencies issuing one set of guidance.
    Responses to questions about the need for harmonization across
Common Rule agencies reflected widespread support for such efforts.
Several commenters acknowledged the difficulty of getting all Common
Rule agencies to agree on all issues, as each has a different mission
and research portfolio. However, they encouraged seeking harmonized
guidance whenever possible.

Regulatory Text

    For the reasons set forth in the preamble, it is proposed that the
Federal Policy for the Protection of Human Subjects be amended as
follows:

PART __PROTECTION OF HUMAN SUBJECTS

__.101 To what does this policy apply?
__.102 Definitions for purposes of this policy.

__.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
__.104 Exempt research.
__.105 Protection of biospecimens and identifiable private
information.
__.106 [Reserved]
__.107 IRB membership.
__.108 IRB functions and operations.
__.109 IRB review of research.
__.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
__.111 Criteria for IRB approval of research.
__.112 Review by institution.
__.113 Suspension or termination of IRB approval of research.
__.114 Cooperative research.
__.115 IRB records.
__.116 General requirements for informed consent.
__.117 Documentation of informed consent.
__.118 Applications and proposals lacking definite plans for
involvement of human subjects.
__.119 Research undertaken without the intention of involving human
subjects.
__.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
__.121 [Reserved]
__.122 Use of Federal funds.
__.123 Early termination of research support: Evaluation of
applications and proposals.
__.124 Conditions.

Sec.  __.101  To what does this policy apply?

    (a) Except as provided in paragraph (b) of this section, and as
detailed in Sec.  __.104, this policy applies to the research described
in paragraphs (a)(1) and (2) of this section. The entities that must
comply with this policy are institutions that are engaged in research
described in paragraphs (a)(1) or (2) of this section, and
institutional review boards (IRBs) reviewing research that is subject
to this policy.
    (1) All research involving human subjects conducted, supported, or
otherwise subject to regulation by any Federal department or agency
that takes appropriate administrative action to make the policy
applicable to such research. This includes research conducted by
Federal civilian employees or military personnel, except that each
department or agency head may adopt such procedural modifications as
may be appropriate from an administrative standpoint. It also includes
research conducted, supported, or otherwise subject to regulation by
the Federal Government outside the United States.
    (2) All clinical trials as defined by this policy, irrespective of
funding source, that meet all of the following conditions:
    (i) The clinical trials are conducted by an institution that
receives support from a Federal department or agency for human subjects
research that is not excluded from this policy under Sec.  __.101(b)(2)
and does not qualify for exemption in accordance with Sec.  __.104;
    (ii) The clinical trials are not subject to regulation by the Food
and Drug Administration; and
    (iii) The clinical trials are conducted at an institution located
within the United States.\1\
---------------------------------------------------------------------------

    \1\ Under this provision, only 45 CFR part 46, subpart A,
applies to all clinical trials meeting the applicable conditions.
This provision does not require clinical trials to comply with the
requirements of 45 CFR part 46, subparts B, C, and D.
---------------------------------------------------------------------------

    (b) The following categories of activities are excluded from this
policy, and no procedural, recordkeeping, or other requirements of this
policy apply to the activities other than the conditions specified for
the relevant category or categories:
    (1) The following activities are excluded because they are deemed
not to be research, as defined in Sec.  __.102(l), for the purposes of
this regulation:
    (i) Data collection and analysis, including the use of
biospecimens, for an institution's own internal operational monitoring
and program improvement purposes, if the data collection and analysis
is limited to the use of data or biospecimens originally collected for
any purpose other than the currently proposed activity, or is obtained
through oral or written communications with individuals (e.g., surveys
or interviews).
    (ii) Oral history, journalism, biography, and historical
scholarship activities that focus directly on the specific individuals
about whom the information is collected.
    (iii) Collection and analysis of data, biospecimens, or records by
or for a criminal justice agency for activities authorized by law or
court order solely for criminal justice or criminal investigative
purposes.
    (iv) Quality assurance or improvement activities involving the
implementation of an accepted practice to improve the delivery or
quality of care or services (including, but not limited to, education,
training, and changing procedures related to care or services) if the
purposes are limited to altering the utilization of the accepted
practice and collecting data or biospecimens to evaluate the effects on
the utilization of the practice. This exclusion does not cover the
evaluation of an accepted practice itself.
    (v) Public health surveillance activities, including the collection
and testing of biospecimens, conducted, supported, requested, ordered,
required, or authorized by a public health authority and limited to
those necessary to allow the public health authority to identify,
monitor, assess, or investigate potential public health signals or the
onset of a disease outbreak, including trends, or signals, and patterns
in diseases, or a sudden increase in injuries from using a consumer
product, or conditions of public health importance, from data, and
including those associated with providing timely situational awareness
and priority setting during the course of an event or crisis that
threatens public health, including natural or man-made disasters.
    (vi) Surveys, interviews, surveillance activities and related
analyses, or the collection and use of biospecimens conducted by a
defense, national security, or homeland security authority solely for
authorized intelligence, homeland security, defense, or other national
security purposes.
    (2) The following activities are excluded because they are
considered to be low-risk human subjects research, when already subject
to independent controls without application of these regulatory
requirements. These exclusions do not apply when the research includes
the collection or analysis of biospecimens. All of the following
exclusion categories apply to research subject to this policy and to
research subject to the additional requirements of 45 CFR part 46,
subparts B, C, and D, however, the exclusion at paragraph (b)(2)(i) of
this section applies only to research subject to subpart D for research
involving educational tests, or observations of public behavior when
the investigator does not participate in the activities being observed.
    (i) Research, not including interventions, that involves the use of
educational tests (cognitive, diagnostic, aptitude, achievement),
survey procedures, interview procedures, or observation of public
behavior (including visual or auditory recording) uninfluenced by the
investigators, if at least one of the following criteria is met:
    (A) The information is recorded by the investigator in such a
manner that human subjects cannot be identified, directly or through
identifiers linked to the subjects;
    (B) Any disclosure of the human subjects' responses outside the
research would not reasonably place the subjects

at risk of criminal or civil liability or be damaging to the subjects'
financial standing, employability, educational advancement, or
reputation; or
    (C) The research will involve a collection of information subject
to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.;
research information will be maintained on information technology that
is subject to and in compliance with section 208(b) of the E-Government
Act of 2002, 44 U.S.C. 3501 note; and all of the information collected,
used, or generated as part of the research will be maintained in a
system or systems of records subject to the Privacy Act of 1974, 5
U.S.C. 552a.
    (ii) Research involving the collection or study of information that
has been or will be acquired solely for non-research activities or were
acquired for research studies other than the proposed research study,
when either of the following two criteria is met:
    (A) These sources are publicly available, or
    (B) The information is recorded by the investigator in such a
manner that human subjects cannot be identified, directly or through
identifiers linked to the subjects, the investigator does not contact
the subjects, and the investigator will not re-identify subjects or
otherwise conduct an analysis that could lead to creating identifiable
private information.
    (iii) Research conducted by a Federal department or agency using
government-generated or government-collected information obtained for
non-research purposes (including criminal history data), if the
information originally involved a collection of information subject to
the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.; the
information is maintained on information technology that is subject to
and in compliance with section 208(b) of the E-Government Act of 2002,
44 U.S.C. 3501 note; and all of the information collected, used, or
generated as part of the research is maintained in a system or systems
of records subject to the Privacy Act of 1974, 5 U.S.C. 552a.
    (iv) Research as defined by this policy that involves only data
collection and analysis involving the recipient's use of identifiable
health information when such use is regulated under 45 CFR parts 160
and 164, subparts A and E, for the purposes of ``health care
operations'' or ``research'' as those terms are defined at 45 CFR
164.501 or for the purpose of ``public health activities'' as described
under 45 CFR 164.512(b).
    (3) The following activities are excluded because they are
considered to be low-risk human subjects research activities that do
not meaningfully diminish subject autonomy. The following exclusion
category applies to research subject to this policy and to research
subject to the additional requirements of 45 CFR part 46, subparts B,
C, or D.
    (i) The secondary research use of a non-identified biospecimen that
is designed only to generate information about an individual that
already is known, including but not limited to the development and
validation of certain tests and assays (such as research to develop a
diagnostic test for a condition using specimens from individuals known
to have the condition and those known not to have the condition),
quality assurance and control activities, and proficiency testing.
    (ii) [Reserved]
    (c) Department or agency heads retain final judgment as to whether
a particular activity is covered by this policy, which judgment shall
be exercised consistent with the ethical principles of the Belmont
Report.\2\
---------------------------------------------------------------------------

    \2\ The National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research, The Belmont Report: Ethical
Principles and Guidelines for the Protection of Human Subjects of
Research (Apr. 18, 1979).
---------------------------------------------------------------------------

    (d) Department or agency heads may require additional protections
for specific research activities or classes of research activities
conducted, supported, or otherwise subject to regulation by the Federal
department or agency but not otherwise covered by this policy. Advance
public notice will be required when those additional requirements apply
to entities outside of the Federal department or agency itself.
    (e) Compliance with this policy requires compliance with pertinent
federal laws or regulations that provide additional protections for
human subjects.
    (f) This policy does not affect any state or local laws or
regulations that may otherwise be applicable and that provide
additional protections for human subjects.
    (g) This policy does not affect any foreign laws or regulations
that may otherwise be applicable and that provide additional
protections to human subjects of research.
    (h) When research covered by this policy takes place in foreign
countries, procedures normally followed in the foreign countries to
protect human subjects may differ from those set forth in this policy.
In these circumstances, if a department or agency head determines that
the procedures prescribed by the institution afford protections that
are at least equivalent to those provided in this policy, the
department or agency head may approve the substitution of the foreign
procedures in lieu of the procedural requirements provided in this
policy. Except when otherwise required by statute, Executive Order, or
the department or agency head, notices of these actions as they occur
will be published in the Federal Register or will be otherwise
published as provided in department or agency procedures.
    (i) Unless otherwise required by law, department or agency heads
may waive the applicability of some or all of the provisions of this
policy to specific research activities or classes of research
activities otherwise covered by this policy provided the alternative
procedures to be followed are consistent with the principles of the
Belmont Report.\3\ Except when otherwise required by statute or
Executive Order, the department or agency head shall forward advance
notices of these actions to the Office for Human Research Protections,
Department of Health and Human Services (HHS), or any successor office,
or to the equivalent office within the appropriate Federal department
or agency, and shall also publish them in the Federal Register or in
such other manner as provided in department or agency procedures. The
waiver notice must include a statement that identifies the conditions
under which the waiver will be applied and a justification as to why
the waiver is appropriate for the research, including how the decision
is consistent with the principles in Belmont Report. Each Federal
department or agency conducting or supporting the research must
establish, on a publicly accessible federal Web site, a list of the
research for which a waiver has been issued.
---------------------------------------------------------------------------

    \3\ Id.
---------------------------------------------------------------------------

    (j) Federal guidance on the requirements of this policy shall be
issued only after consultation, for the purpose of harmonization (to
the extent appropriate), with other Federal departments and agencies
that have adopted this policy, unless such consultation is not
feasible.
    (k) Transition provisions--(1) Research initiated prior to the
compliance dates. Ongoing human subjects research in which human
subjects (as defined by this policy) were involved prior to the
compliance dates for the cited provisions need not comply with the
additional requirements of this subpart at Sec. Sec.  __.101(a)(2),
__.103(e), __.104(c) through (f), __.105, __.108(a)(2), __.109(f)(2),
__.111(a)(7) and (8), __.114, __.115(a)(10) and (11), __.116, and
__.117 that became effective on [effective date of the final rule].

    (2) Use of prior collections of biospecimens. Research involving
the use of prior collections of biospecimens that meets both of the
following criteria need not comply with the requirements of these
regulations:
    (i) The biospecimens were collected for either research or non-
research purposes before the compliance date for the additional
requirements of this subpart at Sec.  __.102(e)(1)(iii), and
    (ii) Research use of the biospecimens occurs only after removal of
any individually identifiable information associated with the
biospecimens.

Sec.  __.102  Definitions for purposes of this policy.

    (a) Certification means the official notification by the
institution to the supporting Federal department or agency component,
in accordance with the requirements of this policy, that a research
project or activity involving human subjects has been reviewed and
approved by an IRB in accordance with an approved assurance.
    (b) Clinical trial means a research study in which one or more
human subjects are prospectively assigned to one or more interventions
(which may include placebo or other control) to evaluate the effects of
the interventions on biomedical or behavioral health-related outcomes.
    (c) Department or agency head means the head of any Federal
department or agency, for example, the Secretary, HHS, and any other
officer or employee of any Federal department or agency to whom the
authority provided to the department or agency head by these
regulations has been delegated.
    (d) Federal department or agency refers to a Federal department or
agency (the department or agency itself rather than its bureaus,
offices or divisions) that takes appropriate administrative action to
make this policy applicable to the research involving human subjects it
conducts, supports, or otherwise regulates (e.g., HHS, the Department
of Defense, or the Central Intelligence Agency).
    (e)(1) Human subject means a living individual about whom an
investigator (whether professional or student) conducting research:
    (i) Obtains data through intervention or interaction with the
individual, and uses, studies, or analyzes the data;
    (ii) Obtains, uses, studies, analyzes, or generates identifiable
private information; or
    (iii) Obtains, uses, studies, or analyzes biospecimens.
    (2) Intervention includes both physical procedures by which data
are gathered (e.g., venipuncture) and manipulations of the subject or
the subject's environment that are performed for research purposes.
    (3) Interaction includes communication or interpersonal contact
between investigator and subject.
    (4) Private information includes information about behavior that
occurs in a context in which an individual can reasonably expect that
no observation or recording is taking place, and information that has
been provided for specific purposes by an individual and that the
individual can reasonably expect will not be shared or made public
(e.g., a medical record or clinically obtained biospecimen).
    (5) Identifiable private information is private information that is
individually identifiable (i.e., the identity of the subject is or may
readily be ascertained by the investigator or associated with the
information).
    (f) Institution means any public or private entity, or department
or agency (including federal, state, and other agencies).
    (g) IRB means an institutional review board established in accord
with and for the purposes expressed in this policy.
    (h) IRB approval means the determination of the IRB that the
research has been reviewed and may be conducted at an institution
within the constraints set forth by the IRB and by other institutional
and federal requirements.
    (i) Legally authorized representative means an individual or
judicial or other body authorized under applicable law to consent on
behalf of a prospective subject to the subject's participation in the
procedure(s) involved in the research.
    (j) Minimal risk means that the probability and magnitude of harm
or discomfort anticipated in the research are not greater in and of
themselves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examinations or
tests. The Secretary of HHS will maintain guidance that includes a list
of activities considered to involve no more than minimal risk. This
list will be re-evaluated no later than every 8 years based on
recommendations from the Federal departments and agencies and the
public.
    (k) Public health authority (consistent with 45 CFR 164.501) means
an agency or authority of the United States, a state, a territory, a
political subdivision of a state or territory, an Indian tribe, or a
foreign government, or a person or entity acting under a grant of
authority from or contract with such public agency, including the
employees or agents of such public agency or its contractors or persons
or entities to whom it has granted authority, that is responsible for
public health matters as part of its official mandate.
    (l) Research means a systematic investigation, including research
development, testing, and evaluation, designed to develop or contribute
to generalizable knowledge. Activities that meet this definition
constitute research for purposes of this policy, whether or not they
are conducted or supported under a program that is considered research
for other purposes. For example, some demonstration and service
programs may include research activities.

Sec.  __.103  Assuring compliance with this policy--research conducted
or supported by any Federal department or agency.

    (a) Each institution engaged in research that is covered by this
policy, with the exception of research excluded from this policy under
Sec.  __.101(b) or eligible for exemption under Sec.  __.104(d), and
that is conducted or supported by a Federal department or agency shall
provide written assurance satisfactory to the department or agency head
that it will comply with the requirements of this policy. In lieu of
requiring submission of an assurance, individual department or agency
heads shall accept the existence of a current assurance, appropriate
for the research in question, on file with the Office for Human
Research Protections, HHS, or any successor office, and approved for
federalwide use by that office. When the existence of an HHS-approved
assurance is accepted in lieu of requiring submission of an assurance,
reports (except certification) required by this policy to be made to
department and agency heads shall also be made to the Office for Human
Research Protections, HHS, or any successor office. Federal departments
and agencies will conduct or support research covered by this policy
only if the institution has provided an assurance that it will comply
with the requirements of this policy, as provided in this section, and
only if the institution has certified to the department or agency head
that the research has been reviewed and approved by an IRB.
    (b) The assurance shall be executed by an individual authorized to
act for the institution and to assume on behalf of the institution the
obligations imposed by this policy and shall be filed in such form and
manner as the department or agency head prescribes.
    (c) The department or agency head may limit the period during which
any assurance shall remain effective or

otherwise condition or restrict the assurance.
    (d) Certification is required when the research is supported by a
Federal department or agency and not otherwise excluded under Sec.
__.101(b), waived under Sec.  __.101(i), or exempted under Sec.
__.104(d), (e), or (f)(2). Institutions shall certify that each
proposal for research covered by this Sec.  __.103 has been reviewed
and approved by the IRB. Such certification must be submitted as
prescribed by the Federal department or agency component supporting the
research. Under no condition shall research covered by this Sec.
__.103 be initiated prior to receipt of the certification that the
research has been reviewed and approved by the IRB.
    (e) For non-exempt research involving human subjects covered by
this policy that takes place at an institution in which IRB oversight
is conducted by an IRB that is not operated by the institution, the
institution and the organization operating the IRB shall establish and
follow procedures for documenting the institution's reliance on the IRB
for oversight of the research and the responsibilities that each entity
will undertake to ensure compliance with the requirements of this
policy (e.g., in a written agreement between the institution and the
IRB, or by implementation of an institution-wide policy directive
providing the allocation of responsibilities between the institution
and an IRB that is not affiliated with the institution).

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.104  Exempt research.

    (a) Unless otherwise required by department or agency heads,
research activities in which the only involvement of human subjects
will be in one or more of the categories in paragraphs (d) through (f)
of this section are not subject to the requirements of this policy,
other than those specified in the category.
    (b) Use of the exemption categories for research subject to the
requirements of subparts B, C, and D. Application of the exemption
categories to research subject to the requirements of 45 CFR part 46,
subparts B, C, and D, is as follows:
    (1) Subpart B. Each of the exemptions at this Sec.  __.104 may be
applied to research conducted under subpart B if the conditions of the
exemption are met.
    (2) Subpart C. The exemptions at this Sec.  __.104 do not apply to
research conducted under subpart C, except for research aimed at a
broader population that consists mostly of non-prisoners but that
incidentally includes some number of prisoners.
    (3) Subpart D. Only the exemptions at paragraphs (d)(1), (2), (4),
(e)(2), and (f)(1) and (2) of this section may be applied to research
conducted under subpart D if the conditions of the exemption are met.
    (c) Federal departments and agencies shall develop a decision tool
to assist in exemption determinations. Unless otherwise required by
law, exemption determinations shall be made by an individual who is
knowledgeable about the exemption categories and who has access to
sufficient information to make an informed and reasonable
determination, or by the investigator or another individual at the
institution who enters accurate information about the proposed research
into the decision tool, which will provide a determination as to
whether the study is exempt. If the decision tool is used, further
assessment or evaluation of the exemption determination is not
required. An institution or, when appropriate, the IRB, must maintain
records of exemption determinations made for research subject to the
requirements of this policy for which the institution or IRB exercises
oversight responsibility. These records must include, at a minimum, the
name of the research study, the name of the investigator, and the
exemption category applied to the research study. Maintenance of the
completed decision tool shall be considered to fulfill this
recordkeeping requirement.
    (1) For studies exempted pursuant to paragraph (d)(2) of this
section, the recordkeeping requirement will be deemed satisfied by the
published list required at paragraph (d)(2)(i) of this section.
    (2) [Reserved].
    (d) The following categories of exempt human subjects research
generally involve a low-risk intervention with human subjects, must be
recorded as required in paragraph (c) of this section, and do not
require application of standards for information and biospecimen
protection provided in Sec.  __.105 or informed consent. Only paragraph
(d)(2) of this section allows for the collection and use of
biospecimens:
    (1) Research conducted in established or commonly accepted
educational settings when it specifically involves normal educational
practices. This includes most research on regular and special education
instructional strategies, and research on the effectiveness of or the
comparison among instructional techniques, curricula, or classroom
management methods that are not likely to adversely impact students'
opportunity to learn required educational content in that educational
setting or the assessment of educators who provide instruction.
    (2) Research and demonstration projects that are conducted or
supported by a Federal department or agency, or otherwise subject to
the approval of department or agency heads, and that are designed to
study, evaluate, or otherwise examine public benefit or service
programs, including procedures for obtaining benefits or services under
those programs, possible changes in or alternatives to those programs
or procedures, or possible changes in methods or levels of payment for
benefits or services under those programs.
    (i) Each Federal department or agency conducting or supporting the
research and demonstration projects must establish, on a publicly
accessible federal Web site or in such other manner as the department
or agency head may prescribe, a list of the research and demonstration
projects that the Federal department or agency conducts or supports
under this provision. The research or demonstration project must be
published on this list prior to or upon commencement of the research.
    (ii) [Reserved]
    (3)(i) Research involving benign interventions in conjunction with
the collection of data from an adult subject through verbal or written
responses (including data entry) or video recording if the subject
prospectively agrees to the intervention and data collection and at
least one of the following criteria is met:
    (A) The information obtained is recorded in such a manner that
human subjects cannot be identified directly or through identifiers
linked to the subjects; or
    (B) Any disclosure of the human subjects' responses outside the
research would not reasonably place the subjects at risk of criminal or
civil liability or be damaging to the subjects' financial standing,
employability, educational advancement, or reputation.
    (ii) For the purpose of this provision, benign interventions are
brief in duration, harmless, painless, not physically invasive, not
likely to have a significant adverse lasting impact on the subjects,
and the investigator has no reason to think the subjects will find the
interventions offensive or embarrassing. If these criteria are met,
such benign interventions might include research activities in which a
subject is asked to read materials, review pictures or videos, play
online games, solve puzzles, or perform cognitive tasks.

    (iii) If the research involves deceiving the subjects regarding the
nature or purposes of the research, this exemption is not applicable
unless the subject authorizes the deception as described in paragraph
(d)(3)(iv) of this section.
    (iv) For the purpose of this provision, authorized deception is
prospective agreement by the subject to participate in research where
the subject is informed that he or she will be unaware of or misled
regarding the nature or purposes of the research.
    (4) Taste and food quality evaluation and consumer acceptance
studies
    (i) If wholesome foods without additives are consumed, or
    (ii) If a food is consumed that contains a food ingredient at or
below the level and for a use found to be safe, or agricultural
chemical or environmental contaminant at or below the level found to be
safe, by the Food and Drug Administration or approved by the
Environmental Protection Agency or the Food Safety and Inspection
Service of the U.S. Department of Agriculture.
    (e) The following categories of exempt human subjects research
allow for the collection of sensitive information about human subjects,
must not involve biospecimens, must be recorded as required in
paragraph (c) of this section, and require application of standards for
information and biospecimen protection provided in Sec.  __.105:
    (1) Research, not including interventions, involving the use of
educational tests (cognitive, diagnostic, aptitude, achievement),
survey procedures, interview procedures, or observation of public
behavior (including visual or auditory recording), if the information
obtained is recorded in such a manner that human subjects can be
identified directly or through identifiers linked to the subjects.
    (2) Secondary research use of identifiable private information that
has been or will be acquired for non-research purposes, if the
following criteria are met:
    (i) Prior notice has been given to the individuals to whom the
identifiable private information pertains that such information may be
used in research; and
    (ii) The identifiable private information is used only for purposes
of the specific research for which the investigator or recipient entity
requested access to the information.
    (f) The following categories of exempt human subjects research
involve biospecimens or identifiable private information, must be
recorded as required in paragraph (c) of this section, require
application of standards for information and biospecimen protection as
described in Sec.  __.105, and require informed consent and limited IRB
review to the extent described in each category or otherwise required
by law:
    (1)(i) Storage or maintenance for secondary research use of
biospecimens or identifiable private information that have been or will
be acquired for research studies other than for the proposed research
study, or for non-research purposes, if the following criteria are met:
    (A) Written consent for the storage, maintenance, and secondary
research use of the information or biospecimens is obtained in
accordance with Sec.  __.116(c) and (d)(2), and the template published
by the Secretary of HHS in accordance with Sec.  __.116(d)(1) must be
used. Oral consent, if obtained during the original data collection and
in accordance with Sec.  __.116(c) and (d)(3), would be satisfactory
for the research use of identifiable private information initially
acquired in accordance with activities excluded from this policy under
Sec.  __.101(b)(2)(i) or exempt from this policy in accordance with
Sec.  __.104(d)(3) or (4), or Sec.  __.104(e)(1);
    (B) The reviewing IRB makes the determinations required by Sec.
__.111(a)(9).
    (ii) [Reserved.]
    (2)(i) Research involving the use of biospecimens or identifiable
private information that have been stored or maintained for secondary
research use, if consent for the storage, maintenance, and secondary
research use of the information and biospecimens was obtained as
detailed in paragraph (f)(1)(i)(A) of this section.
    (ii) If the investigator anticipates that individual research
results will be provided to a research subject, the research may not be
exempted under this provision and must be reviewed by the IRB and
informed consent for the research must be obtained to the extent
required by Sec.  __.116(a) and (b).

Sec.  __.105  Protection of biospecimens and identifiable private
information.

    (a) In General. Institutions and investigators conducting research
that is subject to this policy, or that is exempt from this policy
under Sec.  __.104(e) or (f), involving the collection, storage, or use
of biospecimens or identifiable private information, shall implement
and maintain reasonable and appropriate safeguards as specified in
paragraph (b) of this section to protect biospecimens or identifiable
private information that they collect, obtain, receive, maintain, or
transmit for research. The safeguards shall reasonably protect against
anticipated threats or hazards to the security or integrity of the
information or biospecimens, as well as reasonably protect the
information and biospecimens from any intentional or unintentional use,
release, or disclosure that is in violation of paragraph (c) of this
section. IRB review of the safeguards required by this section is not
required, except to the extent required by Sec.  __.104(f)(1).
    (b) Safeguards requirements. The Secretary of HHS shall establish
and publish for public comment a list of specific measures that the
institution or investigator may implement that will be deemed to
satisfy the requirement for reasonable and appropriate safeguards. The
list will be evaluated as needed, but at least every 8 years, and
amended, as appropriate, after consultation with other Federal
departments and agencies. The institutions and investigators identified
in paragraph (a) of this section shall implement paragraph (a) of this
section by choosing either to apply the safeguards identified by the
Secretary as necessary to protect the security or integrity of and
limit disclosure of biospecimens and electronic and non-electronic
identifiable private information, or to apply safeguards that meet the
standards in 45 CFR 164.308, 164.310, 164.312, and 45 CFR 164.530(c).
For Federal departments and agencies that conduct research activities
that is or will be maintained on information technology that is subject
to and in compliance with section 208(b) of the E-Government Act of
2002, 44 U.S.C. 3501 note, if all of the information collected, used,
or generated as part of the activity will be maintained in systems of
records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and the
research will involve a collection of information subject to the
Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq., these research
activities automatically will be considered in compliance with the
Secretary's reasonable and appropriate safeguards standards, unless or
until any additional safeguards are identified by the Secretary of HHS.
    (c) Limitations on use, release, and disclosure. Unless otherwise
required by law, institutions and investigators shall use or release
biospecimens or use or disclose identifiable private information
collected or maintained for research only:
    (1) For human subjects research regulated by this policy;
    (2) For public health purposes;
    (3) For any lawful purpose with the consent of the subject; or

    (4) For other research purposes if the institution or investigator
has obtained adequate assurances from the recipient that
    (i) The recipient will implement and maintain the level of
safeguards required by paragraph (b) of this section;
    (ii) Except for research that qualifies for exclusion under Sec.
__.101(b) or exemption under Sec.  __.104 the releasing or disclosing
institution or investigator shall obtain documentation from the
recipient that the research has been approved under Sec.  __.111 to the
extent required before releasing biospecimens or disclosing
identifiable private information; and
    (iii) The recipient shall not further release the biospecimens or
disclose identifiable private information except for human subjects
research regulated by this policy, or for other purposes permitted by
this paragraph. For the purposes of this requirement, an institution or
investigator shall obtain adequate assurances through the use of a
written agreement with the recipient that the recipient will abide by
these conditions.
    (d) The provisions of this section do not amend or repeal, and
shall not be construed to amend or repeal, the requirements of 45 CFR
parts 160 and 164 for the institutions or investigators, including
Federal departments or agencies, to which these regulations are
applicable pursuant to 45 CFR 160.102.

Sec.  __.106  [Reserved]

Sec.  __.107  IRB membership.

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

Sec.  __.108  IRB functions and operations.

    (a) In order to fulfill the requirements of this policy each IRB
shall:
    (1) Have access to meeting space and sufficient staff to support
the IRB's review and recordkeeping duties;
    (2) Prepare and maintain a current list of the IRB members
identified by name; earned degrees; representative capacity;
indications of experience such as board certifications or licenses
sufficient to describe each member's chief anticipated contributions to
IRB deliberations; and any employment or other relationship between
each member and the institution, for example, full-time employee, part-
time employee, member of governing panel or board, stockholder, paid or
unpaid consultant;
    (3) Establish and follow written procedures for:
    (i) Conducting its initial and continuing review of research and
for reporting its findings and actions to the investigator and the
institution;
    (ii) Determining which projects require review more often than
annually and which projects need verification from sources other than
the investigators that no material changes have occurred since previous
IRB review; and
    (iii) 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.
    (4) Establish and follow written procedures for ensuring prompt
reporting to the IRB; appropriate institutional officials; the
department or agency head; and the Office for Human Research
Protections, HHS, or any successor office, or the equivalent office
within the appropriate Federal department or agency of
    (i) Any unanticipated problems involving risks to subjects or
others or any serious or continuing noncompliance with this policy or
the requirements or determinations of the IRB; and
    (ii) Any suspension or termination of IRB approval.
    (b) Except when an expedited review procedure is used (as described
in Sec.  __.110), an IRB must 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.  __.109  IRB review of research.

    (a) An IRB shall review and have authority to approve, require
modifications in (to secure approval), or disapprove all research
activities covered by this policy that do not qualify for exemption
pursuant to Sec.  __.104(d), (e), or (f)(2).
    (b) An IRB shall require that information given to subjects as part
of informed consent is in accordance with Sec.  __.116. The IRB may
require that information, in addition to that specifically mentioned in
Sec.  __.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.
    (c) An IRB shall require documentation of informed consent or may
waive documentation in accordance with Sec.  __.117.
    (d) 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.
    (e) An IRB shall conduct continuing review of research requiring
review by

the convened IRB at intervals appropriate to the degree of risk, not
less than once per year, except as described in Sec.  __.109(f).
    (f)(1) Unless an IRB determines otherwise, continuing review of
research is not required in the following circumstances:
    (i) Research eligible for expedited review in accordance with Sec.
__.110;
    (ii) Research that has progressed to the point that it involves
only one or both of the following, which are part of the IRB-approved
study:
    (A) Data analysis, including analysis of identifiable private
information, or
    (B) Accessing follow-up clinical data from procedures that subjects
would undergo as part of standard care for their medical condition; or
    (iii) Research reviewed by the IRB in accordance with the limited
IRB review procedure described in Sec.  __.111(a)(9).
    (2) The IRB must receive confirmation on an annual basis that the
research is still ongoing and that no changes have been made to the
research that would require the IRB to conduct continuing review of the
research.
    (g) An IRB shall have authority to observe or have a third party
observe the consent process and the research.

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.110  Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in approved
research.

    (a) The Secretary of HHS, has established, and published as a
Notice in the Federal Register, a list of categories of research that
may be reviewed by the IRB through an expedited review procedure. The
Secretary will evaluate the list at least every 8 years and amend it,
as appropriate, after consultation with other federal departments and
agencies and after publication in the Federal Register for public
comment. A copy of the list is available from the Office for Human
Research Protections, HHS, or any successor office.
    (b)(1) An IRB may use the expedited review procedure to review the
following:
    (i) Some or all of the research appearing on the list, unless the
reviewer determines that the study involves more than minimal risk;
    (ii) Minor changes in previously approved research during the
period for which approval is authorized; or
    (iii) Research that is being reviewed to determine whether it
qualifies for exemption in accordance with Sec.  __.104(f)(1) in order
to determine that the requirements of Sec.  __.111(a)(9) are satisfied.
    (2) Under an expedited review procedure, the review may be carried
out by the IRB chairperson or by one or more experienced reviewers
designated by the chairperson from among members of the IRB. In
reviewing the research, the reviewers may exercise all of the
authorities of the IRB except that the reviewers may not disapprove the
research. A research activity may be disapproved only after review in
accordance with the non-expedited procedure set forth in Sec.
__.108(b).
    (c) Each IRB that uses an expedited review procedure shall adopt a
method for keeping all members advised of research proposals that have
been approved under the procedure.
    (d) The department or agency head may restrict, suspend, terminate,
or choose not to authorize an institution's or IRB's use of the
expedited review procedure.

Sec.  __.111  Criteria for IRB approval of research.

    (a) In order to approve research covered by this policy the IRB
shall determine that all of the following requirements are satisfied:
    (1) Risks to subjects are minimized:
    (i) By using procedures that are consistent with sound research
design and that do not unnecessarily expose subjects to risk, and
    (ii) Whenever appropriate, by using procedures already being
performed on the subjects for diagnostic or treatment purposes.
    (2) Risks to subjects are reasonable in relation to anticipated
benefits, if any, to subjects, and the importance of the knowledge that
may reasonably be expected to result. In evaluating risks and benefits,
the IRB should consider only those risks and benefits that may result
from the research (as distinguished from risks and benefits of
therapies subjects would receive even if not participating in the
research). The IRB should not consider possible long-range effects of
applying knowledge gained in the research (e.g., the possible effects
of the research on public policy) as among those research risks that
fall within the purview of its responsibility.
    (3) Selection of subjects is equitable. In making this assessment
the IRB should take into account the purposes of the research and the
setting in which the research will be conducted and should be
particularly cognizant of the special problems of research that
involves a category of subjects who are vulnerable to coercion or undue
influence, such as children, prisoners, pregnant women, physically or
mentally disabled persons, or economically or educationally
disadvantaged persons.
    (4) Informed consent will be sought from each prospective subject
or the subject's legally authorized representative, in accordance with,
and to the extent required by, Sec.  __.116.
    (5) Informed consent will be appropriately documented, in
accordance with, and to the extent required by, Sec.  __.117.
    (6) When appropriate, the research plan makes adequate provision
for monitoring the data collected to ensure the safety of subjects.
    (7) When appropriate, there are adequate provisions to protect the
privacy of subjects and to maintain the confidentiality of data, in
addition to the requirements in Sec.  __.105, if the IRB determines
that the standards for information and biospecimen protection in Sec.
__.105 are not sufficient to protect the privacy of subjects and the
confidentiality of data.
    (8) If the investigator proposes a research plan for returning
clinically relevant results to subjects, that the plan is appropriate.
    (9) For purposes of conducting the limited IRB review as required
by Sec.  __.104(f)(1), the IRB need not make the determinations at
paragraphs (a)(1) through (8) of this section, and shall determine that
the following requirements are satisfied:
    (i) The procedures for obtaining broad consent for storage,
maintenance, and secondary research use of biospecimens or identifiable
private information will be conducted in accordance with the
requirements of the first paragraph in Sec.  __.116.
    (ii) If there will be a change for research purposes in the way the
biospecimens or information are stored or maintained, that the privacy
and information protection standards at Sec.  __.105 are satisfied for
the creation of any related storage database or repository.
    (b) When some or all of the subjects are likely to be vulnerable to
coercion or undue influence, such as children, prisoners, pregnant
women, physically or mentally disabled persons, or economically or
educationally disadvantaged persons, additional safeguards have been
included in the study to protect the rights and welfare of these
subjects.

Sec.  __.112  Review by institution.

    Research covered by this policy that has been approved by an IRB
may be subject to further appropriate review and approval or
disapproval by officials of the institution. However, those

officials may not approve the research if it has not been approved by
an IRB.

Sec.  __.113  Suspension or termination of IRB approval of research.

    An IRB shall 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. Any suspension or termination of approval shall include a
statement of the reasons for the IRB's action and shall be reported
promptly to the investigator, appropriate institutional officials, and
the department or agency head.

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.114  Cooperative research.

    (a) Cooperative research projects are those projects covered by
this policy that involve more than one institution. In the conduct of
cooperative research projects, each institution is responsible for
safeguarding the rights and welfare of human subjects and for complying
with this policy.
    (b)(1) Any institution located in the United States that is engaged
in cooperative research must rely upon approval by a single IRB for
that portion of the research that is conducted in the United States.
The reviewing IRB will be selected by the Federal department or agency
supporting or conducting the research or, if there is no funding
agency, by the lead institution conducting the research.
    (2) The following research is not subject to the requirements of
this provision:
    (i) Cooperative research for which more than single IRB review is
required by law; or
    (ii) Research for which the Federal department or agency supporting
or conducting the research determines and documents that the use of a
single IRB is not appropriate for the particular study.
    (c) For research not subject to paragraph (b) of this section, an
institution participating in a cooperative project may enter into a
joint review arrangement, rely on the review of another IRB, or make
similar arrangements for avoiding duplication of effort.

Sec.  __.115  IRB records.

    (a) An institution, or when appropriate an IRB, shall prepare and
maintain adequate documentation of IRB activities, including the
following:
    (1) Copies of all research proposals reviewed, scientific
evaluations, if any, that accompany the proposals, approved sample
consent forms, progress reports submitted by investigators, and reports
of injuries to subjects.
    (2) Minutes of IRB meetings, which shall be in sufficient detail to
show attendance at the meetings; actions taken by the IRB; the vote on
these actions including the number of members voting for, against, and
abstaining; the basis for requiring changes in or disapproving
research; and a written summary of the discussion of controverted
issues and their resolution.
    (3) Records of continuing review activities, including the
rationale for conducting continuing review of research that has
progressed to the point that it involves only one or both of the
following:
    (i) Data analysis, including analysis of identifiable private
information, or
    (ii) Accessing follow-up clinical data from procedures that
subjects would undergo as part of standard care for their medical
condition.
    (4) Copies of all correspondence between the IRB and the
investigators.
    (5) A list of IRB members in the same detail as described in Sec.
__.108(a)(2).
    (6) Written procedures for the IRB in the same detail as described
in Sec.  __.108(a)(3) and (4).
    (7) Statements of significant new findings provided to subjects, as
required by Sec.  __.116(b)(5).
    (8) The rationale for requiring continuing review for research that
otherwise would not require continuing review as described in Sec.
__.109(f)(1).
    (9) The rationale for an expedited reviewer's determination that
research appearing on the expedited review list described in Sec.
__.110(b)(1)(i) is more than minimal risk.
    (10) The written agreement between an institution and an
organization operating an IRB specifying the responsibilities that each
entity will undertake to ensure compliance with the requirements of
this policy, as described in Sec.  __.103(e).
    (11) Records relating to exemption determinations, as described in
Sec.  __.104(c).
    (b) The records required by this policy shall be retained for at
least 3 years, and records relating to research that is conducted shall
be retained for at least 3 years after completion of the research. The
institution or IRB may maintain the records in printed form, or
electronically. All records shall be accessible for inspection and
copying by authorized representatives of the Federal department or
agency at reasonable times and in a reasonable manner.
    (c) The institution or IRB retaining the records shall safeguard
identifiable private information contained within these records in
compliance with Sec.  __.105.

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.116  General requirements for informed consent.

    Except as provided elsewhere in this policy, no investigator may
involve a human subject in research covered by this policy unless the
investigator has obtained the legally effective informed consent of the
subject or the subject's legally authorized representative. An
investigator shall seek such consent only under circumstances that
provide the prospective subject or the representative sufficient
opportunity to consider whether or not to participate and that minimize
the possibility of coercion or undue influence. The information that is
given to the subject or the representative shall be in language
understandable to the subject or the representative. The prospective
subject or the representative must be provided with the information
that a reasonable person would want to have in order to make an
informed decision about whether to participate, and an opportunity to
discuss that information. The information must be presented in
sufficient detail relating to the specific research, and must be
organized and presented in a way that does not merely provide lists of
isolated facts, but rather facilitates the prospective subject's or
representative's understanding of the reasons why one might or might
not want to participate. In obtaining informed consent, the
investigator must present first the information required by this
section, before providing other information, if any, to the subject or
the representative. Any informed consent form must include only the
requirements of informed consent under this section, and appendices
that include any other information provided to the subject or the
representative. If an authorization required by 45 CFR parts 160 and
164 is combined with a consent form, the authorization elements
required by 45 CFR 164.508 must be included in the consent form and not
the appendices. No informed consent, whether oral or written, may
include any exculpatory language through which the subject or the
representative is made to waive or appear to waive any of the subject's
legal rights, or releases or appears to release the investigator, the
sponsor, the institution, or its agents from liability for negligence.

    (a) Basic elements of informed consent. Except as provided in
paragraph (c), (e), or (f) of this section, in seeking informed consent
the following information shall be provided to each subject or the
representative:
    (1) A statement that the study involves research, an explanation of
the purposes of the research and the expected duration of the subject's
participation, a description of the procedures to be followed, and
identification of any procedures that are experimental;
    (2) A description of any reasonably foreseeable risks or
discomforts to the subject;
    (3) A description of any benefits to the subject or to others that
may reasonably be expected from the research;
    (4) A disclosure of appropriate alternative procedures or courses
of treatment, if any, that might be advantageous to the subject;
    (5) A statement describing the extent, if any, to which
confidentiality of records identifying the subject will be maintained;
    (6) For research involving more than minimal risk, an explanation
as to whether any compensation and an explanation as to whether any
medical treatments are available if injury occurs and, if so, what they
consist of, or where further information may be obtained;
    (7) An explanation of whom to contact for answers to pertinent
questions about the research and research subjects' rights, and whom to
contact in the event of a research-related injury to the subject;
    (8) A statement that participation is voluntary, refusal to
participate will involve no penalty or loss of benefits to which the
subject is otherwise entitled, and the subject may discontinue
participation at any time without penalty or loss of benefits to which
the subject is otherwise entitled; and
    (9) One of the following statements about any research that
involves the collection of identifiable private information:
    (i) A statement that identifiers might be removed from the data and
the data that is not identifiable could be used for future research
studies or distributed to another investigator for future research
studies without additional informed consent from the subject or the
representative, if this might be a possibility; or
    (ii) A statement that the subject's data collected as part of the
research, from which identifiers are removed, will not be used or
distributed for future research studies.
    (b) Additional elements of informed consent. Except as provided in
paragraphs (c), (e), or (f) of this section, when appropriate, one or
more of the following elements of information shall also be provided to
each subject or the representative:
    (1) A statement that the particular treatment or procedure may
involve risks to the subject (or to the embryo or fetus, if the subject
is or may become pregnant) that are currently unforeseeable;
    (2) Anticipated circumstances under which the subject's
participation may be terminated by the investigator without regard to
the subject's or the representative's consent;
    (3) Any additional costs to the subject that may result from
participation in the research;
    (4) The consequences of a subject's decision to withdraw from the
research and procedures for orderly termination of participation by the
subject;
    (5) A statement that significant new findings developed during the
course of the research that may relate to the subject's willingness to
continue participation will be provided to the subject;
    (6) The approximate number of subjects involved in the study;
    (7) A statement that the subject's biospecimens may be used for
commercial profit and whether the subject will or will not share in
this commercial profit;
    (8) A statement regarding whether clinically relevant research
results, including individual research results, will be disclosed to
subjects, and if so, under what conditions; and
    (9) An option for the subject or the representative to consent, or
refuse to consent, to investigators re-contacting the subject to seek
additional information or biospecimens or to discuss participation in
another research study.
    (c)(1) Elements of informed consent for broad consent to the
storage, maintenance, and secondary research use of biospecimens or
identifiable private information. If the subject or the representative
will be asked to provide broad consent to the storage or maintenance of
biospecimens or identifiable private information, collected for either
research studies other than the proposed research or non-research
purposes, and the secondary research use of this stored material, the
information required in paragraphs (a)(2), (3), (5), and (7) and, if
applicable, (b)(7) through (9) of this section, shall be provided to
each subject, with the following additional information:
    (i) A general description of the types of research that may be
conducted with information and biospecimens and the information that is
expected to be generated from the research, the types of information or
biospecimens that might be used in research, and the types of
institutions that might conduct research with the biospecimens or
information;
    (ii) A description of the scope of the informed consent must be
provided, including:
    (A) A clear description of the types of biospecimens or information
that were or will be collected and the period of time during which
biospecimen or information collection will occur. This may include all
biospecimens and information from the subject's medical record or other
records existing at the institution at the time informed consent is
sought; and
    (B) For purposes of paragraph (c)(1)(ii)(A) of this section, the
period of time during which biospecimen or information collection will
occur cannot exceed 10 years from the date of consent. For research
involving children as subjects, that time period cannot exceed 10 years
after parental permission is obtained or until the child reaches the
legal age for consent to the treatments or procedures involved in the
research, whichever time period is shorter. The time limitations
described do not apply to biospecimens or information that initially
will be collected for research purposes.
    (iii) A description of the period of time during which an
investigator can continue to conduct research using the subject's
biospecimens and information described in paragraph (c)(1)(ii)(A) of
this section (e.g., a certain number of years, or indefinitely);
    (iv) A statement that participation is voluntary, refusal to
participate will involve no penalty or loss of benefits to which the
subject is otherwise entitled, and that the subject may withdraw
consent, if feasible, for research use or distribution of the subject's
information or biospecimens at any time without penalty or loss of
benefits to which the subject is otherwise entitled, and information
about whom to contact in order for the subject to withdraw consent. The
statement must make clear that information or biospecimens that already
have been distributed for research use may not be retrieved;
    (v) If applicable, a statement notifying the subject or the
representative that the subject or the representative will not be
informed of the details of any specific research studies that might be
conducted, including the purposes of the research, that will use the
subject's information and biospecimens;
    (vi) If applicable, a statement notifying the subject or the

representative of the expectation that the subject's information and
biospecimens are likely to be used by multiple investigators and
institutions and shared broadly for many types of research studies in
the future, and this information and the biospecimens might be
identifiable when shared;
    (vii)The names of the institution or set of institutions at which
the subject's biospecimens or information were or will be collected, to
the extent possible (in recognition that institutions might change
names or cease to exist); and
    (viii) If relevant, an option for an adult subject or the
representative to consent, or refuse to consent, to the inclusion of
the subject's data, with removal of the identifiers listed in 45 CFR
164.514(b)(2)(i)(A) through (Q), in a database that is publicly and
openly accessible to anyone. This option must be prominently noted, and
must include a description of risks of public access to the data.
    (2) [Reserved]
    (d)(1) The Secretary of HHS will establish, and publish in the
Federal Register for public comment, templates for consent that will
contain all of the required elements of informed consent under
paragraph (c) of this section. IRB review of the broad secondary use
informed consent form obtained in accordance with paragraph (c) of this
section is required unless the consent is obtained using only this
template, without any changes.
    (2) If Sec.  __.104(f)(1) requires written consent, the consent for
research use of biospecimens or identifiable private information must
be documented by the use of a written consent form signed by the
subject or the representative. The template for consent for research
use established by the Secretary may serve as the written consent form.
A copy shall be given to the person signing the form.
    (3) If Sec.  __.104(f)(1) allows for oral consent, a subject's or
the representative's oral consent for research use of identifiable
private information must be documented such that the consent is
associated with the subject's identifiable private information. If this
requirement is met through the use of written documentation, the
subject or the representative is not required to sign the
documentation.
    (4) If the subject or the representative declines to consent to the
research use of biospecimens or identifiable private information, this
must be documented appropriately.
    (e)(1) Waiver or alteration of consent in research involving public
benefit and service programs conducted by or subject to the approval of
state or local officials. An IRB may approve a consent procedure that
does not include, or that alters, some or all of the elements of
informed consent set forth above, or waive the above requirement to
obtain informed consent, provided the IRB finds and documents that:
    (i) The research or demonstration project is to be conducted by or
subject to the approval of state or local government officials and is
designed to study, evaluate, or otherwise examine:
    (A) Public benefit or service programs;
    (B) Procedures for obtaining benefits or services under those
programs;
    (C) Possible changes in or alternatives to those programs or
procedures; or
    (D) Possible changes in methods or levels of payment for benefits
or services under those programs; and
    (ii) The research could not practicably be carried out without the
waiver or alteration.
    (2) Additional criteria for waiver or alteration of consent for
biospecimens. For research involving the use of biospecimens, an IRB
may approve a consent procedure that does not include, or that alters,
some or all of the elements of informed consent set forth above, or
waive the above requirements to obtain informed consent, provided the
IRB finds and documents the criteria in paragraph (e)(1) of this
section, and the following additional criteria:
    (i) There are compelling scientific reasons to conduct the
research; and
    (ii) The research could not be conducted with other biospecimens
for which informed consent was obtained or could be obtained.
    (3) If an individual was asked to consent to the storage or
maintenance for secondary research use of biospecimens or identifiable
private information in accordance with the requirements of this section
at paragraph (c) of this section, and refused to consent, an IRB cannot
waive consent for either the storage or maintenance for secondary
research use, or for the secondary research use, of those biospecimens
or information.
    (f)(1) Waiver or alteration of consent. An IRB may approve a
consent procedure that does not include, or that alters, some or all of
the elements of informed consent set forth above, or waive the above
requirements to obtain informed consent, provided the IRB finds and
documents that:
    (i) The research involves no more than minimal risk to the
subjects;
    (ii) The research could not practicably be carried out without the
requested waiver or alteration;
    (iii) If the research involves accessing or using identifiable
biospecimens or identifiable information, the research could not
practicably be carried out without accessing or using identifiers;
    (iv) The waiver or alteration will not adversely affect the rights
and welfare of the subjects; and
    (v) Whenever appropriate, the subjects will be provided with
additional pertinent information after participation.
    (2) Additional criteria for waiver or alteration of consent for
research involving biospecimens. For research involving the use of
biospecimens, an IRB may approve a consent procedure that does not
include, or that alters, some or all of the elements of informed
consent set forth above, or waive the above requirements to obtain
informed consent, provided the IRB finds and documents the criteria in
paragraph (f)(1) of this section, and the following additional
criteria:
    (i) There are compelling scientific reasons for the research use of
the biospecimens; and
    (ii) The research could not be conducted with other biospecimens
for which informed consent was obtained or could be obtained.
    (3) If an individual was asked to consent to the storage or
maintenance for secondary research use of biospecimens or identifiable
private information, in accordance with the requirements of paragraph
(c) of this section, and refused to consent, an IRB cannot waive
consent for either the storage or maintenance for secondary research
use, or for the secondary research use, of those biospecimens or
information.
    (g) An IRB may approve a research proposal in which investigators
obtain, through oral or written communication or by accessing records,
identifiable private information without individuals' informed consent
for the purpose of screening, recruiting, or determining the
eligibility of prospective human subjects of research, provided that
the research proposal includes an assurance that the investigator will
implement standards for protecting the information obtained, in
accordance with and to the extent required by Sec.  __.105.
    (h)(1) A copy of the final version of the informed consent form for
each clinical trial conducted or supported by a Federal department or
agency must be posted by the awardee or the Federal department or
agency component conducting the trial on a publicly available federal
Web site that will be established as a repository for such informed
consent forms . The informed consent form must be posted in such form
and manner as the department or agency head may prescribe, which will

include at a minimum posting, in addition to the informed consent form,
the name of the clinical trial and information about whom to contact
for additional details about the clinical trial.
    (2) The informed consent form must be posted on the federal Web
site within 60 days after the trial is closed to recruitment.
    (i) The informed consent requirements in this policy are not
intended to preempt any applicable Federal, state, or local laws that
require additional information to be disclosed in order for informed
consent to be legally effective.
    (j) Nothing in this policy is intended to limit the authority of a
physician to provide emergency medical care, to the extent the
physician is permitted to do so under applicable federal, state, or
local law.

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.117  Documentation of informed consent.

    (a) Except as provided in paragraph (c) of this section, and except
for research for which consent is obtained in accordance with Sec.
__.116(c), informed consent shall be documented by the use of a written
informed consent form approved by the IRB and signed by the subject or
the subject's legally authorized representative. A copy shall be given
to the person signing the informed consent form.
    (b) Except as provided in paragraph (c) of this section, the
informed consent form may be either of the following:
    (1) A written informed consent form that includes a form containing
only the information required by Sec.  __.116, and appendices that
include any other information. The investigator shall give either the
subject or the subject's legally authorized representative adequate
opportunity to read the informed consent form before it is signed;
alternatively, this form may be read to the subject or the subject's
legally authorized representative.
    (2) A short form written informed consent form stating that the
elements of informed consent required by Sec.  __.116 have been
presented orally to the subject or the subject's legally authorized
representative, and that the information required by Sec.  __.116 was
presented first to the subject, before other information, if any, was
provided. The IRB shall approve a written summary of what is to be said
to the subject or the representative. When this method is used, there
shall be a witness to the oral presentation. Only the short form itself
is to be signed by the subject or the representative. However, the
witness shall sign both the short form and a copy of the summary, and
the person actually obtaining consent shall sign a copy of the summary.
A copy of the summary shall be given to the subject or the
representative, in addition to a copy of the short form.
    (c)(1) An IRB may waive the requirement for the investigator to
obtain a signed informed consent form for some or all subjects if it
finds any of the following:
    (i) That the only record linking the subject and the research would
be the informed consent form and the principal risk would be potential
harm resulting from a breach of confidentiality. Each subject will be
asked whether the subject wants documentation linking the subject with
the research, and the subject's wishes will govern;
    (ii) That the research presents no more than minimal risk of harm
to subjects and involves no procedures for which written consent is
normally required outside of the research context; or
    (iii) If the subjects are members of a distinct cultural group or
community in which signing forms is not the norm, that the research
presents no more than minimal risk of harm to subjects and provided
there is an appropriate alternative mechanism for documenting that
informed consent was obtained. Documentation must include a description
as to why signing forms is not the norm for the distinct cultural group
or community.
    (2) In cases in which the documentation requirement is waived, the
IRB may require the investigator to provide subjects with a written
statement regarding the research.
    (3) This waiver does not apply to research for which consent is
required to be documented in accordance with Sec.  __.116(d)(2), (3),
or (4).
    (4) Documentation of informed consent may not be waived under
paragraphs (c)(1)(i) or (iii) of this section for research subject to
regulation by the Food and Drug Administration unless otherwise
authorized by 21 CFR 56.109(c)(1).

(Approved by the Office of Management and Budget under Control Number.)

Sec.  __.118  Applications and proposals lacking definite plans for
involvement of human subjects.

    Certain types of applications for grants, cooperative agreements,
or contracts are submitted to Federal departments or agencies with the
knowledge that subjects may be involved within the period of support,
but definite plans would not normally be set forth in the application
or proposal. These include activities such as institutional type grants
when selection of specific projects is the institution's
responsibility; research training grants in which the activities
involving subjects remain to be selected; and projects in which human
subjects' involvement will depend upon completion of instruments, prior
animal studies, or purification of compounds. Except for research
excluded under Sec.  __.101(b), waived under Sec.  __.101(i), or
exempted under Sec.  __.104(d), (e), or (f)(2), no human subjects may
be involved in any project supported by these awards until the project
has been reviewed and approved by the IRB, as provided in this policy,
and certification submitted, by the institution, to the Federal
department or agency component supporting the research.

Sec.  __.119  Research undertaken without the intention of involving
human subjects.

    Except for research excluded under Sec.  __.101(b), waived under
Sec.  __.101(i), or exempted under Sec.  __.104(d), (e), or (f)(2), in
the event research is undertaken without the intention of involving
human subjects, but it is later proposed to involve human subjects in
the research, the research shall first be reviewed and approved by an
IRB, as provided in this policy, a certification submitted by the
institution to the Federal department or agency component supporting
the research, and final approval given to the proposed change by the
Federal department or agency component.

Sec.  __.120  Evaluation and disposition of applications and proposals
for research to be conducted or supported by a Federal department or
agency.

    (a) The department or agency head will evaluate all applications
and proposals involving human subjects submitted to the Federal
department or agency through such officers and employees of the Federal
department or agency and such experts and consultants as the department
or agency head determines to be appropriate. This evaluation will take
into consideration the risks to the subjects, the adequacy of
protection against these risks, the potential benefits of the research
to the subjects and others, and the importance of the knowledge gained
or to be gained.
    (b) On the basis of this evaluation, the department or agency head
may approve or disapprove the application or proposal, or enter into
negotiations to develop an approvable one.

Sec.  __.121  [Reserved]

Sec.  __.122  Use of Federal funds.

    Federal funds administered by a Federal department or agency may
not be expended for research involving human subjects unless the
requirements of this policy have been satisfied.

Sec.  __.123  Early termination of research support: Evaluation of
applications and proposals.

    (a) The department or agency head may require that Federal
department or agency support for any project be terminated or suspended
in the manner prescribed in applicable program requirements, when the
department or agency head finds an institution has materially failed to
comply with the terms of this policy.
    (b) In making decisions about supporting or approving applications
or proposals covered by this policy the department or agency head may
take into account, in addition to all other eligibility requirements
and program criteria, factors such as whether the applicant has been
subject to a termination or suspension under paragraph (a) of this
section and whether the applicant or the person or persons who would
direct or has/have directed the scientific and technical aspects of an
activity has/have, in the judgment of the department or agency head,
materially failed to discharge responsibility for the protection of the
rights and welfare of human subjects (whether or not the research was
subject to federal regulation).

Sec.  __.124  Conditions.

    With respect to any research project or any class of research
projects the department or agency head of either the conducting or the
supporting Federal department or agency may impose additional
conditions prior to or at the time of approval when in the judgment of
the department or agency head additional conditions are necessary for
the protection of human subjects.

DEPARTMENT OF HOMELAND SECURITY

6 CFR Part 46

List of Subjects in 6 CFR Part 46

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Department of Homeland
Security proposes to add 6 CFR part 46, as set forth at the end of the
common preamble of this document.

PART 46--PROTECTION OF HUMAN SUBJECTS

Sec.
46.101 To what does this policy apply?
46.102 Definitions for purposes of this policy.
46.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
46.104 Exempt research.
46.105 Protection of biospecimens and identifiable private
information.
46.106 [Reserved]
46.107 IRB membership.
46.108 IRB functions and operations.
46.109 IRB review of research.
46.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
46.111 Criteria for IRB approval of research.
46.112 Review by institution.
46.113 Suspension or termination of IRB approval of research.
46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking definite plans for
involvement of human subjects.
46.119 Research undertaken without the intention of involving human
subjects.
46.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support: Evaluation of
applications and proposals.
46.124 Conditions.

    Authority: 5 U.S.C. 301; Pub. L. 107-296, sec. 102, 306(c); Pub.
L. 108-458, sec. 8306.

Reginald Brothers,
Under Secretary for Science and Technology, DHS.

DEPARTMENT OF AGRICULTURE

7 CFR Part 1c

List of Subjects in 7 CFR Part 1c

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Department of
Agriculture proposes to revise 7 CFR part 1c, as set forth at the end
of the common preamble of this document.

PART 1c--PROTECTION OF HUMAN SUBJECTS

Sec.
1c.101 To what does this policy apply?
1c.102 Definitions for purposes of this policy.
1c.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
1c.104 Exempt research.
1c.105 Protection of biospecimens and identifiable private
information.
1c.106 [Reserved]
1c.107 IRB membership.
1c.108 IRB functions and operations.
1c.109 IRB review of research.
1c.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
1c.111 Criteria for IRB approval of research.
1c.112 Review by institution.
1c.113 Suspension or termination of IRB approval of research.
1c.114 Cooperative research.
1c.115 IRB records.
1c.116 General requirements for informed consent.
1c.117 Documentation of informed consent.
1c.118 Applications and proposals lacking definite plans for
involvement of human subjects.
1c.119 Research undertaken without the intention of involving human
subjects.
1c.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
1c.121 [Reserved]
1c.122 Use of Federal funds.
1c.123 Early termination of research support: Evaluation of
applications and proposals.
1c.124 Conditions.

    Authority:  5 U.S.C. 301.

Catherine Woteki
Under Secretary for Research, Education, and Economics, USDA.

DEPARTMENT OF ENERGY

10 CFR Part 745

List of Subjects in 10 CFR Part 745

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Department of Energy
proposes to revise 10 CFR part 745, as set forth at the end of the
common preamble of this document.

PART 745--PROTECTION OF HUMAN SUBJECTS

Sec.
745.101 To what does this policy apply?
745.102 Definitions for purposes of this policy.
745.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
745.104 Exempt research.
745.105 Protection of biospecimens and identifiable private
information.
745.106 [Reserved]
745.107 IRB membership.
745.108 IRB functions and operations.
745.109 IRB review of research.
745.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.

745.111 Criteria for IRB approval of research.
745.112 Review by institution.
745.113 Suspension or termination of IRB approval of research.
745114 Cooperative research.
745.115 IRB records.
745.116 General requirements for informed consent.
745.117 Documentation of informed consent.
745.118 Applications and proposals lacking definite plans for
involvement of human subjects.
745.119 Research undertaken without the intention of involving human
subjects.
745.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
745.121 [Reserved]
745.122 Use of Federal funds.
745.123 Early termination of research support: Evaluation of
applications and proposals.
745.124 Conditions.

    Authority:  5 U.S.C. 301; 42 U.S.C. 7254.

Elizabeth Sherwood-Randall,
Deputy Secretary of Energy.

NATIONAL AERONAUTICS AND SPACE ADMINISTRATION

14 CFR Part 1230

List of Subjects in 14 CFR Part 1230

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the National Aeronautics
and Space Administration proposes to revise 14 CFR part 1230, as set
forth at the end of the common preamble of this document.

PART 1230--PROTECTION OF HUMAN SUBJECTS

Sec.
1230.101 To what does this policy apply?
1230.102 Definitions for purposes of this policy.
1230.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
1230.104 Exempt research.
1230.105 Protection of biospecimens and identifiable private
information.
1230.106 [Reserved]
1230.107 IRB membership.
1230.108 IRB functions and operations.
1230.109 IRB review of research.
1230.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
1230.111 Criteria for IRB approval of research.
1230.112 Review by institution.
1230.113 Suspension or termination of IRB approval of research.
1230.114 Cooperative research.
1230.115 IRB records.
1230.116 General requirements for informed consent.
1230.117 Documentation of informed consent.
1230.118 Applications and proposals lacking definite plans for
involvement of human subjects.
1230.119 Research undertaken without the intention of involving
human subjects.
1230.120 Evaluation and disposition of applications and proposals
for research to be conducted or supported by a Federal department or
agency.
1230.121 [Reserved]
1230.122 Use of Federal funds.
1230.123 Early termination of research support: Evaluation of
applications and proposals.
1230.124 Conditions.

    Authority:  5 U.S.C. 301.

Richard S. Williams,
Chief Health and Medical Officer.

DEPARTMENT OF COMMERCE

15 CFR Part 27

List of Subjects in 15 CFR Part 27

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Department of Commerce
proposes to revise 15 CFR part 27, as set forth at the end of the
common preamble of this document.

PART 27--PROTECTION OF HUMAN SUBJECTS

Sec.
27.101 To what does this policy apply?
27.102 Definitions for purposes of this policy.
27.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
27.104 Exempt research.
27.105 Protection of biospecimens and identifiable private
information.
27.106 [Reserved]
27.107 IRB membership.
27.108 IRB functions and operations.
27.109 IRB review of research.
27.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
27.111 Criteria for IRB approval of research.
27.112 Review by institution.
27.113 Suspension or termination of IRB approval of research.
27.114 Cooperative research.
27.115 IRB records.
27.116 General requirements for informed consent.
27.117 Documentation of informed consent.
27.118 Applications and proposals lacking definite plans for
involvement of human subjects.
27.119 Research undertaken without the intention of involving human
subjects.
27.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
27.121 [Reserved]
27.122 Use of Federal funds.
27.123 Early termination of research support: Evaluation of
applications and proposals.
27.124 Conditions.

    Authority: 5 U.S.C. 301.

James Hock,
Chief of Staff, Department of Commerce.

SOCIAL SECURITY ADMINISTRATION

20 CFR Part 431

List of Subjects in 20 CFR Part 431

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Social Security
Administration proposes to add 20 CFR part 431, as set forth at the end
of the common preamble of this document.

PART 431--PROTECTION OF HUMAN SUBJECTS

Sec.
431.101 To what does this policy apply?
431.102 Definitions for purposes of this policy.
431.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
431.104 Exempt research.
431.105 Protection of biospecimens and identifiable private
information.
431.106 [Reserved]
431.107 IRB membership.
431.108 IRB functions and operations.
431.109 IRB review of research.
431.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
431.111 Criteria for IRB approval of research.
431.112 Review by institution.
431.113 Suspension or termination of IRB approval of research.
431.114 Cooperative research.
431.115 IRB records.
431.116 General requirements for informed consent.
431.117 Documentation of informed consent.
431.118 Applications and proposals lacking definite plans for
involvement of human subjects.
431.119 Research undertaken without the intention of involving human
subjects.
431.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
431.121 [Reserved]
431.122 Use of Federal funds.
431.123 Early termination of research support: Evaluation of
applications and proposals.
431.124 Conditions.

    Authority: 5 U.S.C. 301; 42 U.S.C. 289(a).

Carolyn W. Colvin,
Acting Commissioner of Social Security.

AGENCY FOR INTERNATIONAL DEVELOPMENT

22 CFR Part 225

List of Subjects in 22 CFR Part 225

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Agency for
International Development proposes to revise 22 CFR part 225, as set
forth at the end of the common preamble of this document.

PART 225--PROTECTION OF HUMAN SUBJECTS

Sec.
225.101 To what does this policy apply?
225.102 Definitions for purposes of this policy.
225.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
225.104 Exempt research.
225.105 Protection of biospecimens and identifiable private
information.
225.106 [Reserved]
225.107 IRB membership.
225.108 IRB functions and operations.
225.109 IRB review of research.
225.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
225.111 Criteria for IRB approval of research.
225.112 Review by institution.
225.113 Suspension or termination of IRB approval of research.
225.114 Cooperative research.
225.115 IRB records.
225.116 General requirements for informed consent.
225.117 Documentation of informed consent.
225.118 Applications and proposals lacking definite plans for
involvement of human subjects.
225.119 Research undertaken without the intention of involving human
subjects.
225.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
225.121 [Reserved]
225.122 Use of Federal funds.
225.123 Early termination of research support: Evaluation of
applications and proposals.
225.124 Conditions.

    Authority:  5 U.S.C. 301.

Wade Warren,
Senior Deputy Assistant Administrator for Global Health, U.S. Agency
for International Development.

DEPARTMENT OF JUSTICE

28 CFR Part 46

AG Order No. 3553-2015

List of Subjects in 28 CFR Part 46

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Department of Justice
proposes to revise 28 CFR part 46, as set forth at the end of the
common preamble of this document.

PART 46--PROTECTION OF HUMAN SUBJECTS

Sec.
46.101 To what does this policy apply?
46.102 Definitions for purposes of this policy.
46.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
46.104 Exempt research.
46.105 Protection of biospecimens and identifiable private
information.
46.106 [Reserved]
46.107 IRB membership.
46.108 IRB functions and operations.
46.109 IRB review of research.
46.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.
46.111 Criteria for IRB approval of research.
46.112 Review by institution.
46.113 Suspension or termination of IRB approval of research.
46.114 Cooperative research.
46.115 IRB records.
46.116 General requirements for informed consent.
46.117 Documentation of informed consent.
46.118 Applications and proposals lacking definite plans for
involvement of human subjects.
46.119 Research undertaken without the intention of involving human
subjects.
46.120 Evaluation and disposition of applications and proposals for
research to be conducted or supported by a Federal department or
agency.
46.121 [Reserved]
46.122 Use of Federal funds.
46.123 Early termination of research support: Evaluation of
applications and proposals.
46.124 Conditions.

    Authority: 5 U.S.C. 301; 28 U.S.C. 509-510.

Sally Quillian Yates,
Deputy Attorney General.

DEPARTMENT OF LABOR

29 CFR Part 21

List of Subjects in 29 CFR Part 21

    Human research subjects, Reporting and record-keeping requirements,
Research.

    For the reasons stated in the preamble, the Social Security
Administration proposes to add 29 CFR part 21, as set forth at the end
of the common preamble of this document.

PART 21--PROTECTION OF HUMAN SUBJECTS

Sec.
21.101 To what does this policy apply?
21.102 Definitions for purposes of this policy.
21.103 Assuring compliance with this policy--research conducted or
supported by any Federal department or agency.
21.104 Exempt research.
21.105 Protection of biospecimens and identifiable private
information.
21.106 [Reserved]
21.107 IRB membership.
21.108 IRB functions and operations.
21.109 IRB review of research.
21.110 Expedited review procedures for certain kinds of research
involving no more than minimal risk, and for minor changes in
approved research.