0338 21cfr601 91 2007

§ 601.90

21 CFR Ch. I (4–1–05 Edition)

(i) Pending. The study has not been
initiated, but does not meet the criterion for delayed.
(ii) Ongoing. The study is proceeding
according to or ahead of the original
schedule described under paragraph
(b)(7) of this section.
(iii) Delayed. The study is behind the
original schedule described under paragraph (b)(7) of this section.
(iv) Terminated. The study was ended
before completion but a final study report has not been submitted to FDA.
(v) Submitted. The study has been
completed or terminated and a final
study report has been submitted to
FDA.
(9) Explanation of the study’s status.
Provide a brief description of the status of the study, including the patient
accrual rate (expressed by providing
the number of patients or subjects enrolled to date, and the total planned
enrollment), and an explanation of the
study’s status identified under paragraph (b)(8) of this section. If the study
has been completed, include the date
the study was completed and the date
the final study report was submitted to
FDA, as applicable. Provide a revised
schedule, as well as the reason(s) for
the revision, if the schedule under
paragraph (b)(7) of this section has
changed since the previous report.
(c) When to report. Annual progress
reports for postmarketing study commitments entered into by applicants
shall be reported to FDA within 60 days
of the anniversary date of the U.S. approval of the application for the product.
(d) Where to report. Submit two copies
of the annual progress report of postmarketing studies to the Center for
Biologics Evaluation and Research or
Center for Drug Evaluation and Research (see mailing addresses in § 600.2
of this chapter).
(e) Public disclosure of information. Except for the information described in
this paragraph, FDA may publicly disclose any information concerning a
postmarketing study, within the meaning of this section, if the agency determines that the information is necessary to identify an applicant or to establish the status of the study including the reasons, if any, for failure to
conduct, complete, and report the

study. Under this section, FDA will not
publicly disclose trade secrets, as defined in § 20.61 of this chapter, or information, described in § 20.63 of this chapter, the disclosure of which would constitute an unwarranted invasion of personal privacy.
[65 FR 64618, Oct. 30, 2000, as amended at 70
FR 14984, Mar. 24, 2005]

Subpart H—Approval of Biological
Products When Human Efficacy Studies Are Not Ethical
or Feasible
SOURCE: 67 FR 37996, May 31, 2002, unless
otherwise noted.

§ 601.90 Scope.
This subpart applies to certain biological products that have been studied
for their safety and efficacy in ameliorating or preventing serious or lifethreatening conditions caused by exposure to lethal or permanently disabling
toxic
biological,
chemical,
radiological, or nuclear substances. This
subpart applies only to those biological
products for which: Definitive human
efficacy studies cannot be conducted
because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substance; and
field trials to study the product’s efficacy after an accidental or hostile exposure have not been feasible. This subpart does not apply to products that
can be approved based on efficacy
standards described elsewhere in FDA’s
regulations (e.g., accelerated approval
based on surrogate markers or clinical
endpoints other than survival or irreversible morbidity), nor does it address
the safety evaluation for the products
to which it does apply.
§ 601.91 Approval based on evidence of
effectiveness from studies in animals.
(a) FDA may grant marketing approval for a biological product for
which safety has been established and
for which the requirements of § 601.90
are met based on adequate and wellcontrolled animal studies when the results of those animal studies establish

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Food and Drug Administration, HHS

§ 601.92

that the biological product is reasonably likely to produce clinical benefit
in humans. In assessing the sufficiency
of animal data, the agency may take
into account other data, including
human data, available to the agency.
FDA will rely on the evidence from
studies in animals to provide substantial evidence of the effectiveness of
these products only when:
(1) There is a reasonably well-understood pathophysiological mechanism of
the toxicity of the substance and its
prevention or substantial reduction by
the product;
(2) The effect is demonstrated in
more than one animal species expected
to react with a response predictive for
humans, unless the effect is demonstrated in a single animal species
that represents a sufficiently wellcharacterized animal model for predicting the response in humans;
(3) The animal study endpoint is
clearly related to the desired benefit in
humans, generally the enhancement of
survival or prevention of major morbidity; and
(4) The data or information on the kinetics and pharmacodynamics of the
product or other relevant data or information, in animals and humans, allows
selection of an effective dose in humans.
(b) Approval under this subpart will
be subject to three requirements:
(1) Postmarketing studies. The applicant must conduct postmarketing
studies, such as field studies, to verify
and describe the biological product’s
clinical benefit and to assess its safety
when used as indicated when such studies are feasible and ethical. Such postmarketing studies would not be feasible until an exigency arises. When
such studies are feasible, the applicant
must conduct such studies with due
diligence. Applicants must include as
part of their application a plan or approach to postmarketing study commitments in the event such studies become ethical and feasible.
(2) Approval with restrictions to ensure
safe use. If FDA concludes that a biological product shown to be effective
under this subpart can be safely used
only if distribution or use is restricted,
FDA will require such postmarketing
restrictions as are needed to ensure

safe use of the biological product, commensurate with the specific safety concerns presented by the biological product, such as:
(i) Distribution restricted to certain
facilities or health care practitioners
with special training or experience;
(ii) Distribution conditioned on the
performance of specified medical procedures, including medical followup; and
(iii) Distribution conditioned on
specified recordkeeping requirements.
(3) Information to be provided to patient
recipients. For biological products or
specific indications approved under
this subpart, applicants must prepare,
as part of their proposed labeling, labeling to be provided to patient recipients. The patient labeling must explain
that, for ethical or feasibility reasons,
the biological product’s approval was
based on efficacy studies conducted in
animals alone and must give the biological product’s indication(s), directions for use (dosage and administration), contraindications, a description
of any reasonably foreseeable risks, adverse reactions, anticipated benefits,
drug interactions, and any other relevant information required by FDA at
the time of approval. The patient labeling must be available with the product
to be provided to patients prior to administration or dispensing of the biological product for the use approved
under this subpart, if possible.
§ 601.92 Withdrawal procedures.
(a) Reasons to withdraw approval. For
biological products approved under this
subpart, FDA may withdraw approval,
following a hearing as provided in part
15 of this chapter, as modified by this
section, if:
(1) A postmarketing clinical study
fails to verify clinical benefit;
(2) The applicant fails to perform the
postmarketing study with due diligence;
(3) Use after marketing demonstrates
that postmarketing restrictions are inadequate to ensure safe use of the biological product;
(4) The applicant fails to adhere to
the postmarketing restrictions applied
at the time of approval under this subpart;
(5) The promotional materials are
false or misleading; or

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