when the research was conducted. This approach acknowledges that
ethical standards have changed over time, and will surely change in the
future. It would also be inequitable to apply contemporary ethical
standards retroactively to research conducted in the past. Before the
effective date of the rule, sponsors or investigators would have had no
notice of the specific standard EPA would apply to their data.
Moreover, they can be assumed to have regarded the ethical standards
prevailing at the time the study was conducted as the most appropriate
benchmark for guiding their conduct. While the proposed rule would,
strictly speaking, only govern EPA's behavior, it provides the basis
for judgment of others' past conduct. It seems inherently unfair to
hold researchers to a standard about which they had no notice and
which, after the fact, they would be unable to comply with through any
further action. But it does seem reasonable and fair to judge their
behavior against the standards of which they should have been aware. We
believe this is the essence of NAS Recommendation 5-7.
    The Agency has refined the language of the standard in NAS
Recommendation 5-7 in two ways. EPA has retained the evidentiary
presumption recommended by the NAS committee, but has modified their
suggested requirement for ``clear and convincing evidence'' to ``clear

evidence.'' The Agency simply cannot imagine ``clear but unconvincing''
evidence that research was fundamentally unethical, and has opted for
brevity. EPA has further modified the recommended standard to specify
that the Agency will consider refusing to rely on a past study when it
is ``significantly deficient'' compared to prevailing ethical
standards. This is intended to acknowledge that minor recordkeeping or
administrative deficiencies with respect to the prevailing ethical
standard should not in themselves force the Agency to set aside an
otherwise ethically conducted and scientifically meritorious study.
    For judging the ethical acceptability of covered human studies
initiated after a final rule becomes effective, EPA proposes the Common
Rule as the primary standard. In general terms, the approach to human
research covered under the extension of EPA's Common Rule would seem
very straightforward. Once EPA completes rulemaking to extend to
certain third-party research the requirements of EPA's Common Rule and
these proposed additional subparts, it seems entirely appropriate to
expect all research within the scope of these subparts and conducted
after they take effect to comply with the rule. If the Agency were to
become aware of covered research that does not comply, EPA should
consider the measures in proposed subpart E of the regulatory text and
discussed in Unit IX., including whether it would be appropriate to
refuse to rely on the data. We believe this is the essence of NAS
Recommendation 5-6.
    EPA is not, of course, proposing to establish FIFRA section
12(a)(2)(P) as a standard. FIFRA section 12(a)(2)(P) was enacted in
1972 and implementing regulations were promulgated in 1980. Thus FIFRA
section 12(a)(2)(P) already applies to human subjects research with
pesticides, and no additional rulemaking is necessary to make it
applicable.
    EPA also agrees with the NAS Recommendation 5-6 that the researcher
should bear the burden of demonstrating compliance with the standard.
Proposed Sec.  26.602 of the regulatory text provides that the Agency
would accept data from a study covered by the rule ``only if EPA has
adequate information to determine that the research was conducted in a
manner that substantially complies with subpart A and, as applicable,
subparts B and D of this part.'' EPA has listed in proposed Sec.
26.124(c) of the regulatory text the kinds of information documenting
the ethical conduct of completed human research that EPA would expect
to see in a submitted report of such research. (Note that this
documentation would be additional to records required by 40 CFR
169.2(j), implementing FIFRA section 12(a)(2)(P) recordkeeping
requirements.) This range of documentation is derived from the Common
Rule criteria for IRB approval of proposed research at 40 CFR 26.111.
It will thus have been gathered for presentation to the IRB and for
submission to EPA with the proposed protocol for the research, and it
should not be a burden to provide the same information to the Agency
with the report on the completed study.
    Today's proposal slightly modifies the standard in NAS
recommendation 5-6 to make it clear that EPA would consider refusing to
rely on a completed human study only if the study fails to
``substantially'' comply with the applicable ethical standards. This
addition reflects EPA's judgment that relatively minor administrative
or recordkeeping deficiencies in a researcher's compliance with a rule
as complex as the Common Rule would not in themselves justify rejecting
otherwise scientifically valuable and ethically conducted research. The
experience of HHS shows that many studies conducted under the Common
Rule fail to meet every applicable provision of the Common Rule, yet
many of these deficiencies are deemed minor. See ``Compliance Oversight
in Human Subjects Protection'' by Dr. Kristina C. Borror, Director,
Division of Compliance Oversight in the Office of Human Research
Protections (February 1, 2005), available at: http://www.hhs.gov/ohrp/sachrp/mtgings/mtg01-05/
 present2/borror--files/frame.htm.

    EPA's proposed subpart F covers all intentional human dosing
studies that EPA is considering under FIFRA or FFDCA. Some of these
studies might not be covered by the proposed extension of EPA's Common
Rule. The exceptions would include any intentional exposure human
studies for pesticides that were not, at the time they were conducted,
intended to be submitted to EPA under FIFRA or FFDCA. Such studies
might be retrieved from the public literature by EPA, conducted by U.S.
States or by foreign governments, or conducted by third parties for
regulatory purposes in other countries. For studies like these, covered
by proposed subpart F but not by the proposed extension of EPA's Common
Rule, the question of what ethical standard to apply is more difficult.
    On the one hand, since the Agency proposes not to subject this
research to the extension of EPA's Common Rule, it could be argued that
it would be inconsistent and unfair to apply the standard of the Common
Rule to the Agency's later decisions about whether to rely on that
research. Sometimes the person submitting a report of research to EPA
will have had no relationship with the sponsor or investigator of the
research; a submitter in this situation could argue that they could be
penalized for actions taken by someone else with no connection to them,
who was not legally required to follow the Common Rule and who for
whatever reason chose not to.
    On the other hand, once EPA promulgates a final rule, researchers
would have notice of the ethical standards EPA would apply in deciding
whether to rely on a completed intentional dosing human study. With
such notice, researchers could make an informed decision whether or not
to comply with the requirements of EPA's Common Rule. They would have
adequate and timely warning about the consequences of noncompliance.
Furthermore, it is EPA's judgment that it is fair to consider the
``prevailing ethical standard'' for research conducted after the
effective date of new rules to be the Common Rule or a foreign
equivalent. These considerations argue for subjecting all research
conducted after the effective date of the new rule to the more
demanding ethical standards defined by that new rule. If EPA took this
approach, its rules might influence the conduct of a larger universe of
research and thereby provide greater protection for human subjects.
    EPA proposes therefore, in deciding whether to rely on data from a
completed study, to apply the Common Rule to all studies conducted
after a final rule becomes effective and which are covered by EPA's new
subpart F, whether or not the research was required to comply with
EPA's Common Rule under EPA's new subpart A. The primary argument
against using the Common Rule as the ethical benchmark for all future
intentional exposure human studies is that researchers will not have
had adequate notice. EPA disagrees; publication of a final rule in the
Federal Register will constitute adequate notice. Given the widespread
awareness of and consensus on the Common Rule as the appropriate guide
for ethical conduct of human research, EPA therefore expects that very
few, if any, sponsors or investigators could credibly claim ignorance
of their ethical responsibilities to protect human subjects. Finally,
the Agency believes its use of the Common Rule as the ethical benchmark
for deciding whether to rely

on a human study would provide additional incentive for researchers to
act ethically.
    Finally, EPA proposes an extraordinary procedure applicable if
scientifically sound but ethically deficient human research is found to
be crucial to EPA's fulfilling its mission to protect public health.
This procedure would also apply if a scientifically sound study covered
by proposed Sec.  26.221 or Sec.  26.421--i.e., an intentional dosing
study involving pregnant women or children as subjects--were found to
be crucial to the protection of public health. The Agency accepts the
NAS advice to make these decisions on a case-by-case basis, taking into
account the particular circumstances of the study and the way it could
affect the regulatory action, and seeking the best possible advice. EPA
agrees such decisions should consider the importance of the research to
a potential regulatory decision, and particularly whether it would
support a regulatory position more protective of public health than
would be justified without reliance on the data. Proposed Sec.  26.603
would require EPA, before deciding not to rely on such data, to seek
the advice of the Human Studies Review Board and comment from the
public.

C. Topics for Public Comment

    The Agency has considered a number of alternatives to the positions
described and invites public comment on whether EPA should adopt any of
these alternatives for the final rule:
    1. Should EPA continue the case-by-case approach articulated in the
February 8, 2005, Federal Register Notice, not adopting by rule ethical
standards to guide decision-making with respect to completed, ethically
problematic human studies?
    2. Should a final rule establish the standard that EPA would rely
on all scientifically sound data from covered intentional exposure
human studies relevant to EPA decision-making, without regard to any
ethical deficiencies in the studies?
    3. Should a final rule establish a different criterion for
acceptance of research conducted before the effective date of the rule
than the criterion proposed in Sec.  26.601 of the regulatory text?
Should a final rule identify specific factors to be considered or
criteria to be applied in determining whether research was
``fundamentally unethical'' or ``significantly deficient with respect
to prevailing standards''?
    4. Should a final rule establish the standard that, in making
decisions under FIFRA and FFDCA, EPA would never rely on data from a
study involving intentional exposure of any human subject to a
pesticide when a purpose of the study was to identify or measure toxic
effects?
    5. Should a final rule establish the standard that EPA would not
rely on an intentional exposure human study covered under proposed
subpart F if the study did not comply with the Common Rule, without
regard to when the research was conducted?
    6. Should a final rule establish the standard in NAS Recommendation
5-7 for all three categories of completed research covered by proposed
subpart F of the regulatory text--i.e., (1) Research conducted before
the rule becomes effective; (2) research conducted after the rule
becomes effective and required to comply with EPA's Common Rule; and
(3) research conducted after the rule becomes effective but not
required to comply with EPA's Common Rule?
    7. Should a final rule apply a different standard to research
conducted after the effective date of the final rule, depending on
whether the research was subject to the requirements of EPA's proposed
subparts A through D?
    8. Should a final rule apply proposed subpart F to a different
range of third-party human research, including any of the categories
discussed in Unit IV., or apply different ethical standards to research
in different categories within an altered scope?
    9. Should a final rule apply a standard other than ``substantial''
compliance with the requirements in EPA's proposed subparts A through
D, perhaps requiring ``full'' or ``complete'' compliance with those
requirements? How should minor, administrative deficiencies be treated
under an alternative standard?
    10. Should a final rule permit use of the exception procedure in
proposed Sec.  26.603 when research falling within the prohibitions of
proposed Sec.  26.221 or Sec.  26.421--i.e., research involving
intentional exposure of pregnant women or children--is deemed crucial
to the protection of public health?
    11. Should a final rule identify additional factors EPA will
consider in deciding whether to rely on a completed human study that
does not meet the appropriate standard in proposed Sec.  26.601 or
Sec.  26.602 of the regulatory text?

XI. EPA's 2006 Appropriations Act

    This unit discusses how this proposed rule meets the requirements
of the Department of the Interior, Environment, and Related Agencies
Appropriations Act, 2006, (Appropriations Act) relating to intentional
dosing human toxicity studies for pesticides. This unit contains six
sections. Section A reviews the provisions of the 2006 Appropriations
Act and summarizes EPA's approach to implementation of its provisions.
Section B addresses the proposed rule's prohibition of intentional
dosing human studies for pesticides when the subjects are pregnant
women, infants, or children. Section C addresses its consistency with
the 2004 NAS report. Section D addresses its consistency with the
Nuremberg Code. Section E addresses its establishment of an independent
Human Studies Review Board. Section F identifies subjects on which EPA
invites public comment.

A. Introduction

    On August 2, 2005, the President signed into law the Department of
the Interior, Environment, and Related Agencies Appropriations Act,
2006, Public Law No. 109-54 (Appropriations Act), which provides
appropriated funds for the Environmental Protection Agency and other
federal departments and agencies. Section 201 of the Appropriations Act
addresses EPA activities regarding intentional dosing human toxicity
studies for pesticides as follows:
    None of the funds made available by this Act may be used by the
Administrator of the Environmental Protection Agency to accept,
consider or rely on third-party intentional dosing human toxicity
studies for pesticides, or to conduct intentional dosing human
toxicity studies for pesticides until the Administrator issues a
final rulemaking on this subject. The Administrator shall allow for
a period of not less than 90 days for public comment on the Agency's
proposed rule before issuing a final rule. Such rule shall not
permit the use of pregnant women, infants or children as subjects;
shall be consistent with the principles proposed in the 2004 report
of the National Academy of Sciences on intentional human dosing and
the principles of the Nuremberg Code with respect to human
experimentation; and shall establish an independent Human Subjects
Review Board. The final rule shall be issued no later than 180 days
after enactment of this Act.

    Consistent with its interpretation of the intent of Congress, EPA
has not waited for the beginning of FY 2006 to discontinue reliance on
third-party intentional human dosing toxicity studies in its decision-
making under FIFRA and FFDCA. In addition, EPA is taking the necessary
steps to ensure such studies will not be accepted or considered after
the beginning of FY 2006 and before a final rule is promulgated. The
Agency has not conducted or supported any intentional dosing human
toxicity studies for pesticides in the past, and has no

intention to conduct them at any time in the future.
    The Agency will concentrate its attention on developing and
promulgating a final rule. As required by the Appropriations Act, EPA
is providing a period of 90 days for the public to comment on this
proposed rule. Because the Appropriations Act directs the Agency to
promulgate a final rule no later than 180 days after enactment (i.e.,
by January 29, 2006), the Agency does not expect to extend the comment
period or to review public comments received after the close of the
comment period.

B. Prohibition of Intentional Dosing Human Studies for Pesticides when
the Subjects are Pregnant Women, Infants, or Children

    This proposed rule would ban third party intentional dosing human
studies for pesticides when the subjects are pregnant women, infants or
children, without regard to whether the studies were intended to
identify or measure a toxic effect. Proposed Sec.  26.220 of the
regulatory text would prohibit, without exception, any third party
performing research covered by the proposed extension of EPA's Common
Rule from ``conducting or supporting research involving intentional
dosing of any pregnant woman, fetus, or newborn.'' Proposed Sec.
26.420 of the regulatory text would prohibit, without exception, any
third party performing research covered by the proposed extension of
EPA's Common Rule from ``conducting or supporting research involving
intentional dosing of any child.'' The same passages would apply the
same prohibitions to EPA, similarly without exception, in any research
it conducts or supports.
    The Agency interprets the phrase ``third-party intentional dosing
human toxicity study for pesticides'' as used in the Appropriations Act
to refer to a subset of all third-party intentional dosing studies
intended for submission to EPA under the pesticide laws, and thus
covered by proposed Sec.  26.101(j) of the regulatory text. Further,
the Agency interprets the phrase ``pregnant women, infants or
children'' as used in the Appropriations Act to have the same scope and
meaning as the phrases ``any pregnant woman, fetus, or newborn'' and
``any child'' in the sections cited above, when taken together. EPA
also notes that the prohibitions in proposed Sec. Sec.  26.220 and
26.420 of the regulatory text reference proposed Sec.  26.101(j), and
therefore make the prohibitions applicable to research that was
conducted with the intent to submit the results to EPA (or hold them
for possible future inspection) under either of the pesticide laws,
FIFRA or FFDCA. EPA interprets the phrase, ``for pesticides'' as used
in the Appropriations Act to mean research that is intended for
consideration by EPA under the pesticide laws, and thus which falls
within the scope of proposed Sec.  26.101(j). EPA invites public
comment on these interpretations of the meaning of the phrase
``intentional dosing human toxicity studies for pesticides'' as it is
used in the Appropriations Act, particularly as it relates to the scope
of the requirement for a prohibition on such studies with subjects who
are ``pregnant women, infants, or children.''

C. Consistency with the 2004 NAS Report

    The Appropriations Act directs EPA to promulgate a rule addressing
third party intentional dosing human toxicity studies for pesticides
that is ``consistent with the principles proposed in the 2004 report of
the National Academy of Sciences on intentional human dosing.''
    Based on a careful review of the NAS report, EPA has concluded that
the underlying principles intended by the NAS committee to be reflected
in its recommendations are the three ``fundamental ethical principles''
identified by the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research (National Commission) in
its report, Ethical Principles and Guidelines for the Protection of
Human Subjects of Research (the ``Belmont Report''). These three
fundamental principles are respect for persons, beneficence, and
justice. See NAS Report at pp. 49-50, 98, and 113-14.
    The NAS committee makes the point clearly that they did not propose
new principles: ``the committee was not required to invent the basic
standards that govern human research in the United States. These
standards are already embodied in the Federal Policy for the Protection
of Human Subjects (the Common Rule.)'' NAS Report pp. 4, 33.
    The NAS committee further stated that the fundamental principles
articulated in the Belmont Report both undergird and are made
operational by the procedural requirements of the Common Rule. The
following quotations express this view:
    Federal regulations incorporate the obligation of beneficence by
requiring IRBs to ensure that risks are minimized to the extent
possible, given the research question, and are reasonable in
relation to potential benefits to the participant or to the
importance of the knowledge to be gained through the research (40
CFR Sec.  26.111(a)(1)-(2)). NAS Report at 56.
    [D]etermining whether the principle of beneficence has been
satisfied requires balancing the anticipated risks to study
participants against the anticipated benefits of the study to
society. The risks to participants must be reasonable in relation to
the societal benefit. In the words of the Common Rule, the risks
must be reasonable in relation to the importance of the knowledge
that may reasonably be expected to result (40 CFR Sec.  26.111
(a)(2)). NAS Report at 107.

    According to the Common Rule, IRBs should not approve a research
protocol involving humans unless `selection of subjects is
equitable' (40 CFR Sec.  26.111(3)). This requirement derives from
the principle of justice identified in the Belmont Report. NAS
Report at 114.
    Voluntary, informed consent by research participants . . . is a
major element in the system of protection of research participants.
The consent requirement expresses the principle of respect for
persons, including respect for and promotion of autonomous choices.
The Common Rule stresses this requirement, as do other codes of
research ethics, including the Nuremberg Code (1949), the
Declaration of Helsinki, and the Good Clinical Practice guidelines.
NAS Report at 120.

    Accordingly, EPA concludes that the ``principles proposed in the
2004 report of the National Academy of Sciences on intentional human
dosing'' are, in fact, the ``three fundamental principles'' of respect
for persons, beneficence, and justice articulated in the Belmont
Report, and that the Common Rule rests on the foundation of those
principles. This proposal to extend the coverage of EPA's Common Rule
to additional categories of regulated third-party research is thus
entirely consistent with those principles.

D. Consistency with the Nuremberg Code

    The Appropriations Act directs EPA to promulgate a rule addressing
third-party intentional dosing human toxicity studies for pesticides
that is ``consistent with . . . the principles of the Nuremberg Code
with respect to human experimentation.''
    The NAS report (p. 47) explains the history of the Nuremberg Code
as follows:
    Public policies regarding the ethical treatment of humans in
research began forming in the late 1940s, largely in response to the
atrocities committed by Nazi investigators who were tried before the
Nuremberg Military Tribunal (United States v. Karl Brandt, et al.)
In 1946, the American Medical Association adopted its first code of
research ethics, which ultimately influenced the Nuremberg
Tribunal's standards for ethical research, embodied in the ten
``basic principles'' for human research now know as the Nuremberg
Code. [footnotes and references omitted]

    The Agency has carefully reviewed this proposed rule, using the 10
principles of the Nuremberg Code as a guide, and has concluded that it
is consistent with them. A full report of this analysis has been placed
in the docket for this proposal.

E. Establishment of a Human Studies Review Board

    The Appropriations Act directs EPA to promulgate a rule that
``shall establish an independent Human Subjects Review Board.''
    EPA believes that the entity required by the Appropriations Act is
intended to be substantially identical to the ``Human Studies Review
Board'' recommended by the NAS in Recommendations 6-1, 6-2, and 6-3 of
the NAS Report. (See discussion in Unit V. of this preamble.)
Consistent with both the requirement of the Appropriations Act and the
recommendations of the NAS, EPA proposes, in proposed Sec.  26.124(b)
of the regulatory text, to establish an independent HSRB. Under this
proposed rule, the review of proposed research by the HSRB would occur
after review by a local IRB and EPA staff. This sequence would be
consistent both with EPA's current practice for reviewing first- and
second-party human research proposals and with the practice of FDA for
reviewing third-party human research proposals. The NAS Report,
however, recommended that the EPA and HSRB reviews come before the IRB
review. EPA believes it has discretion to adopt an approach that
differs in this respect from the NAS recommendation, but seeks public
comment on whether HSRB review would be more effective before or after
local IRB review.

F. Additional Topics for Public Comment

    Although EPA thinks that today's proposal satisfies the provisions
in the Appropriations Act and, in particular, is consistent with the
principles of both the Nuremberg Code and the 2004 NAS Report, the
Agency recognizes that, as a matter of policy, it might be appropriate
to include in the final rule additional provisions arising from either
the Nuremberg Code or the 2004 NAS Report. Therefore, in addition to
the topics identified above, the Agency invites the public to comment
on any specific provisions of either the Nuremberg Code or the 2004 NAS
report that may be appropriate for inclusion in the final rule.

XII. FIFRA Review Requirements

    Pursuant to FIFRA section 25(a), the Agency submitted a draft of
this proposed regulation to the FIFRA Scientific Advisory Panel (SAP),
the U.S. Department of Agriculture (USDA), the Committee on Agriculture
in the House of Representatives, and the Committee on Agriculture,
Nutrition, and Forestry in the United States Senate. In addition, the
Agency submitted a draft of this proposed rule to the Department of
Health and Human Services (HHS).
    The FIFRA SAP waived its review of this proposal because the
significant scientific and ethical issues involved have already been
reviewed by the SAP. (See the report of the SAB/SAP Data from Testing
of Human Subjects Subcommittee in the docket for this proposal and on
the web at: http://www.epa.gov/science1/pdf/ec0017.pdf.) The Agency met

with the staff of the Congressional Committees, and where warranted,
has made changes to the draft proposal based upon those discussions.
    USDA, the U.S. Department of Veterans Affairs, and HHS provided
many helpful comments through the interagency review process, leading
to numerous changes in the draft proposal. In addition, comments dated
August 15, 2005, and August 26, 2005, which EPA received from Cristina
V. Beato, M.D., Acting Assistant Secretary for Health at HHS, have been
placed in the docket for this rulemaking, and are summarized here with
EPA's responses.
    EPA thanks HHS for providing very helpful comments very quickly. In
summary, HHS expressed strong support for EPA's effort to extend the
protections of EPA's Common Rule to research regulated by EPA under
FIFRA. HHS welcomes EPA's decision to adopt additional regulatory
protections of pregnant women, fetuses, newborns, and children,
formalizing EPA's longstanding practice. HHS also welcomes EPA's
proposal to prohibit EPA involvement in or consideration of intentional
exposure studies done to investigate toxic effects.
    HHS made four ``major'' comments. First, HHS stated that it could
not support changes to the content of subpart A, the Common Rule, and
recommended that EPA revise its proposal to incorporate all changes
proposed to Sec. Sec.  26.101, 26.102, and 26.124 in a separate
subpart. EPA appreciates and shares HHS's concern for maintaining
uniformity in subpart A--the regulation common to all the Common Rule
departments and agencies--and promises that the final rule will
accomplish the extension of EPA's Common Rule without altering the
common text. We have not made the requested change in this proposal
because we want first to solicit public comment on how best to achieve
clarity in our codification of these new requirements. Would the
requirements applicable to regulated third parties be best expressed as
HHS has suggested, in a separate subpart of 40 CFR part 26, or would it
be clearer if all the requirements applying to regulated third parties
were codified together in an entirely separate part, after the model of
the FDA rules at 21 CFR parts 50 and 56?
    Second, HHS notes in their August 15 written comment that FDA may
have additional comments, but did not have time to complete them in the
greatly compressed scheduled imposed by the demands of the
Appropriations Act. FDA's comments were received on August 26, and this
proposal has been amended to reflect all their suggested clarifications
and changes. The Agency would also welcome additional comments from HHS
and FDA, and will address them in the final rule.
    Third, HHS recommends that EPA modify its proposal to incorporate a
ban on research involving intentional exposure of prisoners, parallel
to the bans proposed on similar research involving pregnant women,
fetuses, newborns, and children. EPA has specifically requested public
comment on this suggestion in Unit VIII., and will seriously consider
adopting such a ban in the final rule.
    The final major HHS comment expresses concern that the ethical
standard proposed in Sec.  26.601 of the regulatory text, to be applied
to research conducted before the effective date of new EPA rules, may
be too permissive, and ``fails to provide helpful guidance on what
would separate an acceptable study from an unacceptable one.'' The
standard EPA has proposed, as explained in Unit X., is based on the
advice of the NAS committee, which thought long and hard about this
issue. EPA, too, has thought a great deal about this criterion, and has
identified several topics for public comment at the end of Unit X.,
including the specific points raised by HHS in this comment. We will
consider all these comments in deciding on a standard for the final
rule.
    In addition to the four ``major'' comments discussed above, HHS
provided 23 additional ``specific'' comments. Although some of the
passages HHS cited in the draft proposal they reviewed do not appear in
this published proposal, EPA has adopted all the specific suggestions
for clarifications and rewording suggested by HHS. The final HHS
comment, however, questions whether submission to EPA of reports of
completed research

should be made mandatory when the research proposal has been reviewed
and approved by EPA. EPA has not proposed this, because FIFRA section
6(a)(2) already requires any applicant for registration or registrant
of a pesticide to provide to EPA any ``additional factual information
concerning adverse effects of a pesticide'' that it becomes aware of.
It is EPA's interpretation that it would be a violation of this
provision for a regulated third party to refuse to submit a report upon
completion of research which EPA had approved as a proposal in order to
suppress ``additional factual information concerning adverse effects.''

XIII. Statutory and Executive Order Reviews

A. Executive Order 12866

    Under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993), the Office of Management and
Budget (OMB) determined that this proposed rule is a ``significant
regulatory action'' under section 3(f) of the Executive Order because
this action might raise novel legal or policy issues. Accordingly, EPA
submitted this proposed rulemaking to OMB for review under Executive
Order 12866 and any changes made in response to OMB comments have been
documented in the public docket for this rulemaking as required by
section 6(a)(3)(E) of the Executive Order.
    In addition, EPA has prepared an economic analysis of the potential
costs and benefits associated with this proposed action, which is
contained in a document entitled Economic Analysis of Proposed Human
Studies Rule. A copy of this document is available in the public docket
for this proposed rule and is briefly summarized here.
    The analysis describes the benefits of the proposed rulemaking in
qualitative terms. These benefits included greater protections for test
subjects, and a corresponding reduction in their risks, to the extent
that affected researchers are not already following the Common Rule.
The benefits to sponsors of third-party human research include a better
understanding of the standards that EPA will apply in determining
whether to rely on the results of their studies, and thus, the
opportunity to design and perform studies that are more likely to meet
EPA standards, leading to more efficient Agency reviews. The Agency
believes the general public will benefit from the proposed rule because
the rule will strengthen the protections for human subjects and
reinforce the Agency's strong commitment to base its decisions on
scientifically sound information.
    The analysis also estimates the costs of the proposed rule by
focusing on the costs to third parties of complying with the new
requirements and the costs to EPA of implementing the new requirements.
In general, EPA believes that most, if not all, third-party research
intended for submission to EPA that involves intentional exposure of
human subjects already complies with the Common Rule or an equivalent
foreign standard. For purposes of this analysis, EPA assumed that
current practice was in full compliance with the Common Rule. In
contrast, EPA assumed that other types of third-party human research do
not comply with the Common Rule, although it is likely that many
responsible for such research are aware of and do follow Common Rule
principles relating to informed consent and IRB review.
    After reviewing the history of EPA's consideration of research
involving human subjects in its various program offices, EPA estimates
that the proposed rule would affect only a limited number of third-
party studies involving human subjects each year. EPA also collected
data on the cost per study of compliance with the Common Rule. These
costs include preparing documents to support review by an IRB and the
expense associated with the IRB review. These costs are very minor
relative to the overall cost of conducting the studies. For EPA, the
costs are associated with the review of protocols and the review of
completed human studies by EPA staff and the Human Studies Review
Board.
    EPA evaluated a range of options, from no action to an expansive
rule. The first option was not to promulgate any rule, thereby
continuing the current practice. All other options evaluated would
apply to third-party human research that was conducted with the intent
to submit the results to EPA under either FIFRA or FFDCA. The second
option consisted of extending the requirements of EPA's Common Rule to
such third-party human research only when it involved intentional
exposure studies for the purpose of identifying or quantifying a toxic
effect. The third option, which reflects the rule being proposed, would
extend the requirements of EPA's Common Rule to all third-party
intentional exposure human studies intended for submission under FIFRA
or FFDCA. Option 4 would extend the requirements of EPA's Common Rule
to all third-party human research intended for submission under the
pesticide laws. All of the latter three options include a requirement
for third parties to submit protocols for review prior to initiating
the types of human research covered by the Common Rule. Finally,
options 2-4 include a provision prohibiting the Agency and third
parties from conducting covered human research with pregnant women or
children as subjects.
    For all of the options, the potential costs of the proposed rule to
third-party researchers and EPA are estimated to be very low, both
because the number of affected studies is relatively small and because
the costs of compliance with the Common Rule are low. Where the option
simply reflects the current practice (option 1) the added total
incremental costs to third-party sponsors of human research are zero.
EPA assumes that currently the pesticide industry is already spending
$159,000 to $196,000 annually to comply with the Common Rule for
intentional exposure human studies and the Agency is currently spending
$113,000 a year to review, on a case-by-case basis, the ethical aspects
of such studies. Option 2 would add an estimated total annual
incremental cost to third parties of $7,532, and an estimated annual
cost to EPA of $220,894. Option 3 would add an estimated total annual
incremental cost to third parties of $16,140, and an estimated annual
cost to EPA of $327,630. Option 4 would add an estimated total annual
incremental cost to third parties of $202,700 to $242,796, and an
estimated annual cost to EPA of $601,134. The higher estimated costs
for option 4 reflect the Common Rule compliance burden on third-party
researchers who perform human studies not involving intentional
exposure of human subjects, and the costs for EPA to review such
completed studies and protocols for intentional exposure studies.
    The proposed rule, if finalized as proposed, is estimated to result
in a total annual incremental cost to third parties of approximately
$16,000, and an estimated annual cost to EPA of approximately $328,000.

B. Paperwork Reduction Act

    The information collection requirements in this proposed rule have
been submitted to the Office of Management and Budget (OMB) under the
Paperwork Reduction Act, 44 U.S.C. 3501 et seq. The Information
Collection Request (ICR) document prepared by EPA has been assigned EPA
ICR No. 2195.01, and a copy of the ICR has been placed in the public
docket for this proposed rule.
    This new information collection activity is planned to ensure that
sound

and appropriate scientific data are available to EPA when making
regulatory decisions, and to protect the interests, rights and safety
of those individuals that are participants in the type of research
activity that is the subject of this proposed rule. Specifically, this
new information collection activity consists of proposed reporting and
recordkeeping requirements. Whenever respondents intend to conduct
research for submission to EPA under the pesticide laws that involves
intentional dosing of human subjects, they will be required to submit
study protocols to EPA and a cognizant local IRB before such research
is initiated so that the scientific design and ethical standards that
will be employed during the proposed study may be reviewed and
approved. Respondents will also be required to submit information about
the ethical conduct of completed research that involved intentional
dosing of human subjects when such research is submitted to EPA.
    Some responses to this collection of information will be required
in order to obtain or retain a benefit (i.e., a pesticide
registration). Other responses will be voluntarily submitted at the
initiative of the regulated entity. The information collection activity
described in the ICR will be initiated by respondents as a condition of
EPA's consideration of the research when it is subsequently submitted
to EPA.
    FIFRA sections 3(c)(1)(F) and 3(c)(2)(B) authorize EPA to require
various data in support of a pesticide's continued registration or an
application for a new or amended pesticide registration. FIFRA section
12(a)(2)(P) forbids any person ``to use any pesticide in tests on human
beings unless such human beings (i) are fully informed of the nature
and purposes of the test and of any physical and mental health
consequences which are reasonably foreseeable therefrom, and (ii)
freely volunteer to participate in the test.''
    An agency may not conduct or sponsor, and a person is not required
to respond to an information collection request unless it displays a
currently valid OMB control number. The OMB control numbers for EPA's
regulations codified in Chapter 40 of the CFR, after appearing in the
preamble of the final rule, are listed in 40 CFR part 9 for display
purposes, and are also included on any related collection instrument
(e.g., the form or survey instrument).
    EPA anticipates that respondents will submit 30 studies that
involve intentional dosing of human subjects under FIFRA or FFDCA to
EPA per year and that the preparation of the required information will
require about 32 hours per study for a total estimated annual burden
hours for affected entities of 960 hours, representing a total
estimated annual paperwork cost of $440,160. It is important to note
that this total annual paperwork burden and cost estimate includes
activities related to initial rule familiarization, as well as
activities that researchers already perform and would continue to
perform even without the Agency's rulemaking in this area (i.e.,
developing a protocol and maintaining records). The average annual
burden on EPA for reviewing this information for each study submission
is estimated to be 80 hours per study, representing a paperwork related
labor cost of about $14,672 per response and a total annual cost of
$440,160.
    Under the PRA, ``burden'' means the total time, effort, or
financial resources expended by persons to generate, maintain, retain,
or disclose or provide information to or for a Federal agency. This
includes the time needed to review instructions; develop, acquire,
install, and utilize technology and systems for the purposes of
collecting, validating, and verifying information, processing and
maintaining information, and disclosing and providing information;
adjust the existing ways to comply with any previously applicable
instructions and requirements; train personnel to be able to respond to
a collection of information; search data sources; complete and review
the collection of information; and transmit or otherwise disclose the
information.
    Direct your comments on the Agency's need for this information, the
accuracy of the provided burden estimates, and any suggested methods
for minimizing respondent burden, including the use of automated
collection techniques, to EPA using the public docket that has been
established for this proposed rule (docket ID number OPP-2003-0132) at
http://www.epa.gov/edocket/. In addition, send a copy of your comments

about the ICR to OMB at: Office of Information and Regulatory Affairs,
Office of Management and Budget, 725 17th St., NW., Washington, DC
20503, Attention: Desk Office for EPA ICR No. 2195.01. Since OMB is
required to complete its review of the ICR between 30 and 60 days after
September 12, 2005, please submit your ICR comments for OMB
consideration to OMB by October 12, 2005.
    The Agency will consider and address comments received on the
information collection requirements contained in this proposal when it
develops the final rule.

C. Regulatory Flexibility Act

    Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA),
5 U.S.C. 601 et seq., after considering the potential economic impacts
of today's proposed rule on small entities, the Agency hereby certifies
that this proposal will not have a significant adverse economic impact
on a substantial number of small entities. This determination is based
on the Agency's economic analysis performed for this rulemaking, which
is summarized in Unit XIII.A., and a copy of which is available in the
public docket for this rulemaking. The following is a brief summary of
the factual basis for this certification.
    Small entities include small businesses, small organizations, and
small governmental jurisdictions. For purposes of assessing the impacts
of today's proposed rule on small entities, small entity is defined in
accordance with the RFA as: (1) A small business as defined by the
Small Business Administration's (SBA) regulations at 13 CFR 121.201;
(2) a small governmental jurisdiction that is a government of a city,
county, town, school district, or special district with a population of
less than 50,000; and (3) a small organization that is any not-for-
profit enterprise which is independently owned and operated and is not
dominant in its field.
    As discussed in Unit XIII.A., the total annual cost to researchers
covered by this proposed rule is estimated to be $16,000, or under $600
per study. This is a trivially small portion of the overall cost of
performing such studies, each of which is estimated to cost from
$125,000 to $500,000. After reviewing the history of EPA's
consideration on human research in its various program offices, EPA
estimates that the proposed rule would affect only a limited number of
third-party human studies each year. Because both the number of
affected studies is relatively small and the costs of compliance with
the Common Rule are low, the potential overall costs to third parties
are also small. Although we cannot predict whether or how many small
entities might engage in the subject matter research in the future, the
Agency expects that there will be no or minimal impact from this
proposed rule on small entities.
    We continue to be interested in the potential impacts of the
proposed rule on small entities and welcome comments on all aspects
related to such impacts.

D. Unfunded Mandates Reform Act

    Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA)
(Public Law 104-4), EPA has determined that this action does not
contain a Federal mandate that may result in expenditures of $100
million or more for State, local, and tribal governments, in the
aggregate, or the private sector in any one year. As described in Unit
XIII.A., the estimated total costs associated with this action are
approximately $16,000 per year. This cost represents the incremental
cost to researchers attributed to the additional procedural
requirements contained in this proposal. Based on historical
submissions, EPA has determined that State, local, and tribal
governments rarely perform human research intended for submission to
EPA under FIFRA or FFDCA. In addition, the proposed rule is not
expected to significantly or uniquely affect small governments.
Accordingly, this action is not subject to the requirements of sections
202 and 205 of UMRA.

E. Executive Order 13132

    Pursuant to Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999), EPA has determined that this proposed rule
does not have ``federalism implications,'' because it will not have
substantial direct effects on the states, on the relationship between
the national government and the states, or on the distribution of power
and responsibilities among the various levels of government, as
specified in the Order. As indicated earlier, instances where a state
performs human research intended for submission to EPA under FIFRA or
FFDCA are extremely rare. Therefore, this proposed rule may seldom
affect a state government. Thus, Executive Order 13132 does not apply
to this proposed rule. In the spirit of the Order, and consistent with
EPA policy to promote communications between the Agency and State and
local governments, EPA specifically solicits comment on this proposed
rule from State and local officials.

F. Executive Order 13175

    As required by Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (59 FR 22951, November 6,
2000), EPA has determined that this proposed rule does not have tribal
implications because it will not have substantial direct effects on
tribal governments, on the relationship between the Federal government
and the Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes, as
specified in the Order. As indicated previously, instances where a
tribal government performs human research intended for submission to
EPA under FIFRA or FFDCA are extremely rare. Thus, Executive Order
13175 does not apply to this proposed rule. In the spirit of the Order,
and consistent with EPA policy to promote communications between the
Agency and State and local governments, EPA specifically solicits
comment on this proposed rule from tribal officials.

G. Executive Order 13045

    Executive Order 13045, entitled Protection of Children from
Environmental Health Risks and Safety Risks (62 FR 19885, April 23,
1997) does not apply to this proposed rule because this action is not
designated as an ``economically significant'' regulatory action as
defined by Executive Order 12866 (see Unit XIII.A.). Further, this
proposal does not establish an environmental standard that is intended
to have a negatively disproportionate effect on children. To the
contrary, this action will provide added protections for children who
may participate in the research covered by the proposed rule.

H. Executive Order 13211

    This proposed rule is not subject to Executive Order 13211,
entitled Actions Concerning Regulations that Significantly Affect
Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001) because
it is not likely to have any significant adverse effect on the supply,
distribution, or use of energy.

I. National Technology Transfer and Advancement Act

    Section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), 15 U.S.C. 272 note) directs EPA to use voluntary
consensus standards in its regulatory activities unless to do so would
be inconsistent with applicable law or impractical. Voluntary consensus
standards are technical standards (e.g., materials specifications, test
methods, sampling procedures) that are developed or adopted by
voluntary consensus standards bodies. NTTAA directs EPA to provide
Congress, through OMB, with explanations when the Agency decides not to
use available and applicable voluntary consensus standards. This action
does not propose to require specific methods or standards to generate
those data. Therefore, this proposed rule does not impose any technical
standards that would require Agency consideration of voluntary
consensus standards. The Agency invites comment on its conclusion
regarding the applicability of voluntary consensus standards to this
proposed rulemaking.

J. Executive Order 12898

    This proposed rule does not have an adverse impact on the
environmental and health conditions in low-income and minority
communities. Therefore, under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994), the Agency has
not considered environmental justice-related issues. Although not
directly impacting environmental justice-related concerns, the
provisions of the proposed rule would require researchers to use
procedures to ensure equitable selection of test subjects in covered
human research.

XIV. Effective Date

    EPA considers the expeditious application of these new protections
to be in the public interest and accordingly proposes to provide no
longer period than is essential between publication of a final rule and
its effective date. The Agency believes a longer transition period is
not likely to be necessary in light of the relatively few studies
affected by this proposal.
    FIFRA section 25(a)(4), 7 U.S.C. 136w(a)(4), provides that:
    Simultaneously with the promulgation of any rule or regulation
under this Act, the Administrator shall transmit a copy thereof to
the Secretary of the Senate and the Clerk of the House of
Representatives. The rule or regulation shall not become effective
until the passage of 60 calendar days after the rule or regulation
is so transmitted.

    Since this regulation would be issued under the authority of FIFRA,
this requirement defines the minimum time lapse after promulgation
before a final rule could become effective. EPA thus proposes that the
final rule would be effective 60 days after its promulgation and
transmittal to Congress. EPA invites public comment on the timing of
the effective date of the final rule.

List of Subjects in 40 CFR Part 26

    Environmental protection, Human research subjects, Reporting and
recordkeeping requirements.

    Dated: September 6, 2005.
Stephen L. Johnson,
Administrator.

    Therefore, it is proposed that 40 CFR chapter I be amended as
follows:

PART 26--[AMENDED]

    1. By revising the authority citation for part 26 to read as
follows:

    Authority: 5 U.S.C. 301; 7 U.S.C. 136w(a)(1); 21 U.S.C.
346a(e)(1)(C); and 42 U.S.C. 300v-1(b).

    2. By redesignating Sec. Sec.  26.101 through 26.124 as subpart A
and adding a new subpart heading to read as follows:

Subpart A--Basic Federal Policy for Protection of Human Research
Subjects

    3. By amending Sec.  26.101 by adding paragraphs (j) and (k) to
read as follows:

Sec.  26.101  To what does this policy apply?

* * * * *
    (j) Except as provided in paragraphs (a) and (b) of this section,
this policy applies to all research involving intentional exposure of a
human subject if, at any time prior to initiating such research, any
person who conducted or supported such research intended:
    (1) To submit results of the research to EPA for consideration in
connection with any regulatory action that may be performed by EPA
under the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C.
136 et seq.) or section 408 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 346a); or
    (2) To hold the results of the research for later inspection by EPA
under the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C.
136 et seq.) or section 408 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 346a).
    (k) For purposes of determining a person's intent under paragraph
(j) of this section, EPA may consider any available information
relevant to determining the intent of a person who conducts or supports
research with human subjects after the effective date of the rule. EPA
shall rebuttably presume such intent existed if:
    (1) The person or the person's agent has submitted or made
available for inspection the results of such research to EPA; or
    (2) The person is a member of a class of people who, or whose
products or activities, are regulated by EPA under FIFRA or the FFDCA
and, at the time the research was initiated, the results of the
research would be relevant to EPA's exercise of its authority under
FIFRA or the FFDCA with respect to that class of people, products, or
activities.
    4. By amending Sec.  26.102 by adding paragraph (k) to read as
follows:

Sec.  26.102  Definitions.

* * * * *
    (k) Research involving intentional exposure of a human subject
means a study of an environmental substance in which the exposure to
the substance experienced by a human subject participating in the study
would not have occurred but for the human subject's participation in
the study.
    5. By revising Sec.  26.124 to read as follows:

Sec.  26.124  Conditions.

    (a) With respect to any research project or any class of research
projects the department or agency head 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.
    (b) Prior submission and review of proposed human research. Any
person who intends to conduct human research covered by Sec.  26.101(j)
shall, after receiving approval from all appropriate IRBs, submit to
EPA at least 90 days prior to initiating such research all information
relevant to the proposed research specified by Sec.  26.115(a) to be
prepared and maintained by an IRB, and the following additional
information, to the extent not otherwise covered:
    (1) A discussion of:
    (i) The potential risks to human subjects;
    (ii) The measures proposed to minimize risks to the human subjects;
    (iii) The expected benefits of such research, and to whom they
would accrue;
    (iv) Alternative means of obtaining information comparable to what
would be collected through the proposed research; and
    (v) The distribution and balance of risks and benefits of the
proposed research.
    (2) The information for subjects and written informed consent
agreements as provided to the IRB, and as approved by the IRB.
    (3) Information about how subjects will be recruited, including any
advertisements proposed to be used.
    (4) All correspondence between the IRB and the investigators or
sponsors.
    (5) Following initial evaluation of the protocol by Agency staff,
EPA shall submit the protocol and all supporting materials, together
with the staff evaluation, to the Human Studies Review Board. This
Board shall consist of members who are not employed by the Agency, who
meet the ethics requirements for special government employees, and who
have expertise in fields appropriate for review of human research. The
Board shall review and comment on the scientific and ethical aspects of
research proposals and reports of completed intentional dosing research
with human subjects which EPA intends to rely on in its decision-making
under FIFRA or FFDCA, and, on request, advise EPA on ways to strengthen
its programs for protection of human subjects of research.
    (c) Submission of information pertaining to ethical conduct of
completed human research. Any person who submits to EPA data derived
from human research covered by this subpart shall also provide to EPA
information documenting compliance with the requirements of this
subpart. Such information should include:
    (1) Copies of all of the records relevant to the research specified
by Sec.  26.115(a) to be prepared and maintained by an IRB.
    (2) Copies of sample records used to document informed consent as
specified by Sec.  26.117, but not identifying any subjects of the
research.
    (3) Copies of all correspondence, if any, between EPA and the
researcher or sponsor pursuant to paragraph (b) of this section.
    6. By adding new subparts B through F to read as follows:
Subpart B--Additional Protections for Pregnant Women, Fetuses, and
Newborns Involved in Research
Sec.
Sec.  26.201 To what do these regulations apply?
Sec.  26.202 Definitions.
Sec.  26.203 Duties of IRBs in connection with research involving
pregnant women, fetuses, and neonates.
Sec.  26.204 Research involving pregnant women or fetuses.
Sec.  26.205 Research involving neonates.
Sec.  26.206 Research involving, after delivery, the placenta, the
dead fetus, or fetal material.
Sec.  26.207-26.219 [Reserved]
Sec.  26.220 Prohibition of research involving intentional dosing of
pregnant women, fetuses, or newborns.
Sec.  26.221 Prohibition of EPA reliance on research involving
intentional dosing of pregnant women, fetuses, or newborns.
Subpart C--Additional Protections Pertaining to Research Involving
Prisoners as Subjects [Reserved]
Subpart D--Additional Protections for Children Involved as Subjects in
Research
Sec.  26.401 To what do these regulations apply?
Sec.  26.402 Definitions.
Sec.  26.403 IRB duties.
Sec.  26.404 Research not involving greater than minimal risk.
Sec.  26.405 Research involving greater than minimal risk but
presenting the prospect of direct benefit to the individual
subjects.
Sec.  26.406 [Reserved]
Sec.  26.407 [Reserved]

Sec.  26.408 Requirements for permission by parents or guardians and
for assent by children.
Sec.  26.409-26.419 [Reserved]
Sec.  26.420 Prohibition of research involving intentional dosing of
children.
Sec.  26.421 Prohibition of EPA reliance on research involving
intentional dosing of children.
Subpart E--Administrative Actions for Noncompliance
Sec.  26.501 Lesser administrative actions.
Sec.  26.502 Disqualification of an IRB or an institution.
Sec.  26.503 Public disclosure of information regarding revocation.
Sec.  26.504 Reinstatement of an IRB or an institution.
Sec.  26.505 Debarment.
Sec.  26.506 Actions alternative or additional to disqualification.
Subpart F--Ethical Standards for Assessing Whether to Rely on the
Results of Human Research in EPA Regulatory Decisions
Sec.  26.601 Human research conducted prior to [effective date of
the final rule].
Sec.  26.602 Human research conducted after [effective date of the
final rule].
Sec.  26.603 Exceptions for human research.

Subpart B--Additional Protections for Pregnant Women, Fetuses, and
Newborns Involved in Research

Sec.  26.201  To what do these regulations apply?

    (a) Except as provided in paragraph (b) of this section, this
subpart applies to all research involving pregnant women, human
fetuses, neonates of uncertain viability, or nonviable neonates
conducted or supported by the Environmental Protection Agency (EPA).
This includes all research conducted in EPA facilities by any person
and all research conducted in any facility by EPA employees. This
subpart also applies to all research involving pregnant women, human
fetuses, neonates of uncertain viability, or nonviable neonates covered
by Sec.  26.101(j).
    (b) The exemptions at Sec.  26.101(b)(1) through (b)(6) are
applicable to this subpart.
    (c) The provisions of Sec.  26.101(c) through (i) are applicable to
this subpart. Reference to State or local laws in this subpart and in
Sec.  26.101(f) is intended to include the laws of federally recognized
American Indian and Alaska Native Tribal Governments.
    (d) The requirements of this subpart are in addition to those
imposed under the other subparts of this part.

Sec.  26.202  Definitions.

    The definitions in Sec.  26.102 shall be applicable to this subpart
as well. In addition, the definitions at 45 CFR 46.202(a) through (f)
and at 45 CFR 46.202(h) are applicable to this subpart. For purposes of
this part, Administrator means the Administrator of the Environmental
Protection Agency and any other officer or employee of the
Environmental Protection Agency to whom authority has been delegated.

Sec.  26.203  Duties of IRBs in connection with research involving
pregnant women, fetuses, and neonates.

    The provisions of 45 CFR 46.203 are applicable to this section.

Sec.  26.204   Research involving pregnant women or fetuses.

    The provisions of 45 CFR 46.204 are applicable to this section.

Sec.  26.205  Research involving neonates.

    The provisions of 45 CFR 46.205 are applicable to this section.

Sec.  26.206  Research involving, after delivery, the placenta, the
dead fetus, or fetal material.

    The provisions of 45 CFR 46.206 are applicable to this section.

Sec.  26.207-26.219  [Reserved]

Sec.  26.220  Prohibition of research involving intentional dosing of
pregnant women, fetuses, or newborns.

    Notwithstanding any other provision of this part, under no
circumstances shall EPA or a person when covered by Sec.  26.101(j)
conduct or support research involving intentional dosing of any
pregnant woman, fetus, or newborn.

Sec.  26.221  Prohibition of EPA reliance on research involving
intentional dosing of pregnant women, fetuses, or newborns.

    In its regulatory decision-making under the Federal Insecticide,
Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.) or section 408 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a), EPA shall
not rely on any research involving intentional dosing of any pregnant
women, fetuses, or newborns, except when such research is deemed
scientifically sound and crucial to the protection of public health,
under the procedure defined in Sec.  26.603.

Subpart C--Additional Protections Pertaining to Research Involving
Prisoners as Subjects [Reserved]

Subpart D--Additional Protections for Children Involved as Subjects
in Research

Sec.  26.401  To what do these regulations apply?

    (a) This subpart applies to all research involving children as
subjects, conducted or supported by EPA. This subpart also applies to
all research involving children covered by Sec.  26.101(j).
    (1) This includes research conducted by EPA employees, except that
each head of an Office of the Agency may adopt such nonsubstantive,
procedural modifications as may be appropriate from an administrative
standpoint.
    (2) It also includes research conducted or supported by EPA outside
the United States, but in appropriate circumstances, the Administrator
may, under Sec.  26.101(e), waive the applicability of some or all of
the requirements of these regulations for research of this type.
    (b) Exemptions at Sec.  26.101(b)(1) and (b)(3) through (b)(6) are
applicable to this subpart. The exemption at Sec.  26.101(b)(2)
regarding educational tests is also applicable to this subpart.
However, the exemption at Sec.  26.101(b)(2) for research involving
survey or interview procedures or observations of public behavior does
not apply to research covered by this subpart, except for research
involving observation of public behavior when the investigator(s) do
not participate in the activities being observed.
    (c) The exceptions, additions, and provisions for waiver as they
appear in Sec.  26.101(c) through (i) are applicable to this subpart.

Sec.  26.402  Definitions.

    The definitions in Sec.  26.102 shall be applicable to this subpart
as well. In addition, as used in this subpart:
    (a) Children are persons who have not attained the age of 18.
    (b) Assent means a child's affirmative agreement to participate in
research. Mere failure to object should not, absent affirmative
agreement, be construed as assent.
    (c) Permission means the agreement of parent(s) or guardian to the
participation of their child or ward in research.
    (d) Parent means a child's biological or adoptive parent.
    (e) Guardian means an individual who is authorized under applicable
State, Tribal, or local law to consent on behalf of a child to general
medical care.

Sec.  26.403  IRB duties.

    The provisions of 45 CFR 46.403 are applicable to this section.

Sec.  26.404  Research not involving greater than minimal risk.

    EPA will conduct or fund research in which the IRB finds that no
greater than minimal risk to children is presented, only if the IRB
finds that adequate provisions are made for soliciting the assent of
the children and the

permission of their parents or guardians, as set forth in Sec.  26.408.

Sec.  26.405  Research involving greater than minimal risk but
presenting the prospect of direct benefit to the individual subjects.

    EPA will conduct or fund research in which the IRB finds that more
than minimal risk to children is presented by an intervention or
procedure that holds out the prospect of direct benefit for the
individual subject, or by a monitoring procedure that is likely to
contribute to the subject's well-being, only if the IRB finds and
documents that:
    (a) The risk is justified by the anticipated benefit to the
subjects.
    (b) The relation of the anticipated benefit to the risk is at least
as favorable to the subjects as that presented by available alternative
approaches.
    (c) Adequate provisions are made for soliciting the assent of the
children and permission of their parents or guardians, as set forth in
Sec.  26.408.

Sec.  26.406  [Reserved]

Sec.  26.407  [Reserved]

Sec.  26.408  Requirements for permission by parents or guardians and
for assent by children.

    (a) In addition to the determinations required under other
applicable sections of this subpart, the IRB shall determine that
adequate provisions are made for soliciting the assent of the children,
when in the judgment of the IRB the children are capable of providing
assent. In determining whether children are capable of assenting, the
IRB shall take into account the ages, maturity, and psychological state
of the children involved. This judgment may be made for all children to
be involved in research under a particular protocol, or for each child,
as the IRB deems appropriate. If the IRB determines that the capability
of some or all of the children is so limited that they cannot
reasonably be consulted or that the intervention or procedure involved
in the research holds out a prospect of direct benefit that is
important to the health or well-being of the children and is available
only in the context of the research, the assent of the children is not
a necessary condition for proceeding with the research. Even where the
IRB determines that the subjects are capable of assenting, the IRB may
still waive the assent requirement under circumstances in which consent
may be waived in accord with Sec.  26.116(d).
    (b) In addition to the determinations required under other
applicable sections of this subpart, the IRB shall determine, in
accordance with and to the extent that consent is required by Sec.
26.116, that adequate provisions are made for soliciting the permission
of each child's parents or guardian. Where parental permission is to be
obtained, the IRB may find that the permission of one parent is
sufficient for research to be conducted under Sec. 26.404 or
Sec. 26.405.
    (c) In addition to the provisions for waiver contained in Sec.
26.116, if the IRB determines that a research protocol is designed for
conditions or for a subject population for which parental or guardian
permission is not a reasonable requirement to protect the subjects (for
example, neglected or abused children), it may waive the consent
requirements in subpart A of this part and paragraph (b) of this
section, provided an appropriate mechanism for protecting the children
who will participate as subjects in the research is substituted, and
provided further that the waiver is not inconsistent with Federal,
State or local law. The choice of an appropriate mechanism would depend
upon the nature and purpose of the activities described in the
protocol, the risk and anticipated benefit to the research subjects,
and their age, maturity, status, and condition.
    (d) Permission by parents or guardians shall be documented in
accordance with and to the extent required by Sec.  26.117.
    (e) When the IRB determines that assent is required, it shall also
determine whether and how assent must be documented.

Sec. Sec.  26.409-26.419  [Reserved]

Sec.  26.420  Prohibition of research involving intentional dosing of
children.

    Notwithstanding any other provision of this part, under no
circumstances shall EPA or a person when covered by Sec.  26.101(j)
conduct or support research involving intentional dosing of any child.

Sec.  26.421  Prohibition of EPA reliance on research involving
intentional dosing of children.

    In its regulatory decision-making under the Federal Insecticide,
Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.) or section 408 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a), EPA shall
not rely on any research involving intentional dosing of any child,
except when such research is deemed scientifically sound and crucial to
the protection of public health, under the procedure defined in Sec.
26.603.

Subpart E--Administrative Actions for Noncompliance

Sec.  26.501  Lesser administrative actions.

    (a) If apparent noncompliance with the applicable regulations in
subparts A through D of this part concerning the operation of an IRB is
observed by a duly authorized investigator during an inspection, the
inspector will present an oral or written summary of observations to an
appropriate representative of the IRB. EPA may subsequently send a
letter describing the noncompliance to the IRB and to the parent
institution. The agency will require that the IRB or the parent
institution respond to this letter within a time period specified by
EPA and describe the corrective actions that will be taken by the IRB,
the institution, or both to achieve compliance with these regulations.
    (b) On the basis of the IRB's or the institution's response, EPA
may schedule a reinspection to confirm the adequacy of corrective
actions. In addition, until the IRB or the parent institution takes
appropriate corrective action, the Agency may:
    (1) Withhold approval of new studies subject to the requirements of
this part that are conducted at the institution or reviewed by the IRB;
    (2) Direct that no new subjects be added to ongoing studies subject
to this part;
    (3) Terminate ongoing studies subject to this part when doing so
would not endanger the subjects; or
    (4) When the apparent noncompliance creates a significant threat to
the rights and welfare of human subjects, notify relevant State and
Federal regulatory agencies and other parties with a direct interest in
the agency's action of the deficiencies in the operation of the IRB.
    (c) The parent institution is presumed to be responsible for the
operation of an IRB, and EPA will ordinarily direct any administrative
action under this subpart against the institution. However, depending
on the evidence of responsibility for deficiencies, determined during
the investigation, EPA may restrict its administrative actions to the
IRB or to a component of the parent institution determined to be
responsible for formal designation of the IRB.

Sec.  26.502  Disqualification of an IRB or an institution.

    (a) Whenever the IRB or the institution has failed to take adequate
steps to correct the noncompliance stated in the letter sent by the
Agency under Sec.  26.501(a) and the EPA Administrator determines that
this noncompliance may justify the

disqualification of the IRB or of the parent institution, the
Administrator may institute appropriate proceedings.
    (b) The Administrator may disqualify an IRB or the parent
institution if the Administrator determines that:
    (1) The IRB has refused or repeatedly failed to comply with any of
the regulations set forth in this part, and
    (2) The noncompliance adversely affects the rights or welfare of
the human subjects of research.
    (c) If the Administrator determines that disqualification is
appropriate, the Administrator will issue an order that explains the
basis for the determination and that prescribes any actions to be taken
with regard to ongoing human research, covered by subparts A through D
of this part, conducted under the review of the IRB. EPA will send
notice of the disqualification to the IRB and the parent institution.
Other parties with a direct interest, such as sponsors and
investigators, may also be sent a notice of the disqualification. In
addition, the agency may elect to publish a notice of its action in the
Federal Register.
    (d) EPA may refuse to consider in support of a regulatory decision
the data from human research, covered by subparts A through D of this
part, that was reviewed by a disqualified IRB or conducted at a
disqualified institution, unless the IRB or the parent institution is
reinstated as provided in Sec.  26.504, or unless such research is
deemed scientifically sound and crucial to the protection of public
health, under the procedure defined in Sec.  26.603.

Sec.  26.503  Public disclosure of information regarding revocation.

    A determination that EPA has disqualified an institution and the
administrative record regarding that determination are disclosable to
the public under 40 CFR part 2.

Sec.  26.504  Reinstatement of an IRB or an institution.

    An IRB or an institution may be reinstated if the Administrator
determines, upon an evaluation of a written submission from the IRB or
institution that explains the corrective action that the institution or
IRB plans to take, that the IRB or institution has provided adequate
assurance that it will operate in compliance with the standards set
forth in this part. Notification of reinstatement shall be provided to
all persons notified under Sec.  26.501(c).

Sec.  26.505  Debarment.

    If EPA determines that an institution or investigator repeatedly
has not complied with or has committed an egregious violation of the
applicable regulations in subparts A through D of this part, EPA may
recommend that institution or investigator be declared ineligible to
participate in EPA-supported research (debarment). Debarment will be
initiated in accordance with procedures specified at 40 CFR part 32.

Sec.  26.506  Actions alternative or additional to disqualification.

    Disqualification of an IRB or of an institution is independent of,
and neither in lieu of nor a precondition to, other statutorily
authorized proceedings or actions. EPA may, at any time, on its own
initiative or through the Department of Justice, institute any
appropriate judicial proceedings (civil or criminal) and any other
appropriate regulatory action, in addition to or in lieu of, and
before, at the time of, or after, disqualification. The Agency may also
refer pertinent matters to another Federal, State, or local government
agency for any action that that agency determines to be appropriate.

Subpart F--Ethical Standards for Assessing Whether to Rely on the
Results of Human Research in EPA Regulatory Decisions

Sec.  26.601  Human research conducted prior to [effective date of the
final rule].

    Unless there is clear evidence that the conduct of that research
was fundamentally unethical (e.g., the research was intended to
seriously harm participants or failed to obtain informed consent), or
was significantly deficient relative to the ethical standards
prevailing at the time the research was conducted, EPA will generally
accept and rely on relevant, scientifically valid data from research
that:
    (a) Was initiated prior to [effective date of the final rule],
    (b) Involved intentional exposure of a human subject,
    (c) Did not involve intentional exposure of a pregnant woman,
fetus, newborn, or child, and
    (d) Is being considered under the Federal Insecticide, Fungicide,
and Rodenticide Act or the Federal Food, Drug, and Cosmetic Act.

Sec.  26.602  Human research conducted after [effective date of the
final rule].

    EPA will generally accept and rely on relevant, scientifically
valid data from research that:
    (a) Was initiated after [effective date of the final rule],
    (b) Involved intentional exposure of a human subject,
    (c) Did not involve intentional exposure of a pregnant woman,
fetus, newborn, or child, and
    (d) Is being considered under the Federal Insecticide, Fungicide,
and Rodenticide Act or the Federal Food, Drug, and Cosmetic Act only if
EPA has adequate information to determine that the research was
conducted in a manner that substantially complies with subparts A
through D of this part.

Sec.  26.603  Exceptions for human research.

    (a) Before reaching a decision not to rely on scientifically useful
and relevant data derived from research that does not meet the
applicable standards of Sec. Sec.  26.601 through 26.602, or that
involves intentional exposure of a pregnant woman, fetus, newborn, or
child, EPA will consider whether the data are crucial to a regulatory
decision that would be more protective of public health than could be
justified without relying on the data.
    (b) Before making a decision under this section, EPA will solicit
the views of the Human Studies Review Board and provide an opportunity
for public comment.
    (c) If EPA decides to rely on data derived from a study that does
not meet the applicable standards of Sec. Sec.  26.601 through 26.602,
EPA will include in the explanation of its decision a thorough
discussion of the significant ethical deficiencies of the study, as
well as the full rationale for concluding that relying on the study is
crucial to protection of public health.
[FR Doc. 05-18010 Filed 9-8-05; 9:19 am]

BILLING CODE 6560-50-S


[Federal Register Volume 85, Number 246 (Tuesday, December 22, 2020)]
[Notices]
[Pages 83546-83547]
[FR Doc No: 2020-28244]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Project No. 1904-078]

Great River Hydro, LLC; Notice Establishing Procedural Schedule
for Licensing and Deadline for Submission of Final Amendments

    Take notice that the following amended hydroelectric application
has been filed with the Commission and is available for public
inspection.
    a. Type of Application: New Major License.
    b. Project No.: 1904-078.
    c. Date Material Amendments Filed: December 7, 2020.
    d. Applicant: Great River Hydro, LLC (Great River Hydro).
    e. Name of Project: Vernon Hydroelectric Project.
    f. Location: The existing project is located on the Connecticut
River in Windham County, Vermont, and Cheshire County, New Hampshire.
There are no federal lands within the project boundary.
    g. Filed Pursuant to: Federal Power Act, 16 U.S.C. 791(a)-825(r).
    h. Applicant Contact: John Ragonese, FERC License Manager, Great
River Hydro, LLC, 40 Pleasant Street, Suite 202, Portsmouth, NH 03801;
(603) 498-2851 or<EMAIL_ADDRESS>    i. FERC Contact: Steve Kartalia,<PHONE_NUMBER> or
<EMAIL_ADDRESS>    j. This application is not ready for environmental analysis at this
time.
    k. Great River Hydro filed an application for a new license for the
Vernon Hydroelectric Project No. 1904 on May 1, 2017. In the license
application, Great River Hydro stated that it could not develop a
complete licensing proposal for the project since many of the required
environmental studies were not complete as of May 1, 2017. Great River
Hydro indicated that it would amend the license application after
completing additional field work, consultation, and analyses on the
required studies. Great River Hydro filed material amendments to the
final license application on December 7, 2020.
    l. Project Description: The existing Vernon Project consists of:
(1) A 956-foot-long, 58-foot-high concrete dam that includes: (a) 356-
foot-long section integral to the powerhouse; and (b) a 600-foot-long
overflow spillway section that includes: (i) A 9-foot-high, 6-foot-wide
downstream fishway sluice; (ii) a 13-foot-high, 13-foot-wide trash/ice
sluice; (iii) two 20-foot-high, 50-foot-wide tainter gates; (iv) four
10-foot-high, 50-foot-wide tainter gates; (v) two 10-foot-high, 50-
foot-wide hydraulic panel bays; (vi) two 10-foot-high, 50-foot-wide
stanchion bays; (vii) a 10-foot-high, 42.5-foot-wide stanchion bay; and
(viii) eight 7-foot-high, 9-foot-wide hydraulic flood gates; (2) a 26-
mile-long, 2,550-acre impoundment with a useable storage volume of
18,300 acre-feet between elevations 212.13 and 220.13 feet National
Geodetic Vertical Datum of 1929 (NGVD 29); (3) eight approximately 30-
foot-high trashracks with 1.75-inch clear bar spacing and two
approximately 30-foot-high trashracks with 3.625-inch clear bar
spacing; (4) a 356-foot-long, 55-foot-wide, 45-foot-high reinforced
concrete, steel, and brick powerhouse containing four 2-megawatt (MW)
vertical Francis turbine-generator units, four 4-MW vertical Kaplan
turbine-generator units, and two 4.2-MW vertical Francis turbine-
generator units, for a total project capacity of 32.4 MW; (5) ten
concrete draft tubes ranging from 16 to 27 feet in diameter; (6) a 500-
foot-long, 13.8-kilovolt underground generator lead that connects the
turbine-generator units to two step-up transformers; (7) a 984-foot-
long, 15-foot-wide upstream fishway; and (8) appurtenant facilities.
    Great River Hydro operates the project in coordination with its
upstream Wilder Project No. 1892 and Bellows Falls Project No. 1855 and
in a peaking mode. Average annual generation is approximately 158,028
MW-hours. Great River Hydro is proposing changes to project operation
that would reduce impoundment fluctuations and increase the stability
of downstream flow releases relative to current project operation,
including targeted water surface elevation levels and flow ramping
rates. Great River Hydro proposes several protection, mitigation, and
enhancement measures for aquatic, terrestrial, cultural, and recreation
resources, and threatened and endangered species. The specific proposed
changes are described in the amended application.
    m. In addition to publishing the full text of this notice in the
Federal Register, the Commission provides all interested persons an
opportunity to view and/or print the contents of this notice, as well
as other documents in the proceeding (e.g., license application) via
the internet through the Commission's Home Page (http://www.ferc.gov)
using the eLibrary link. Enter the docket number excluding the last
three digits in the docket number field to access the document (P-
1904). At this time, the Commission has suspended access to the
Commission's Public Reference Room due to the proclamation declaring a
National Emergency concerning the Novel Coronavirus Disease (COVID-19)
issued by the President on March 13, 2020. For assistance, contact FERC
at<EMAIL_ADDRESS>or call toll-free,<PHONE_NUMBER> or
(202) 502-8659 (TTY).
    n. You may also register online at https://ferconline.ferc.gov/FERCOnline.aspx to be notified via email of new filings and issuances
related to this or other pending projects. For assistance, contact FERC
Online Support.
    o. Procedural Schedule: The application will be processed according
to the following preliminary Hydro Licensing Schedule. Revisions to the
schedule may be made as appropriate.

------------------------------------------------------------------------
                  Milestone                           Target date
------------------------------------------------------------------------
Commission issues letter identifying           January 2021.
 application deficiencies and requesting
 additional information.
Notice of Acceptance/Notice of Ready for       May 2021.
 Environmental Analysis.
Filing of recommendations, preliminary terms   July 2021.
 and conditions, and fishway prescriptions.

Reply Comments due...........................  August 2021.
------------------------------------------------------------------------

    p. Final amendments to the application must be filed with the
Commission no later than 30 days from the issuance date of the notice
of ready for environmental analysis.

    Dated: December 16, 2020.
Kimberly D. Bose,
Secretary.
[FR Doc. 2020-28244 Filed 12-21-20; 8:45 am]
BILLING CODE 6717-01-P