0338 21cfr601 70 2007

Food and Drug Administration, HHS

§ 601.70
(1) Manufacturing methods or processes, including quality control procedures.
(2) Production, sales, distribution,
and similar data and information, except that any compilation of such data
and information aggregated and prepared in a way that does not reveal
data or information which is not available for public disclosure under this
provision is available for public disclosure.
(3) Quantitative or semiquantitative
formulas.
(g) For purposes of this regulation,
safety and effectiveness data include
all studies and tests of a biological
product on animals and humans and all
studies and tests on the drug for identity, stability, purity, potency, and
bioavailability.

unless extraordinary circumstances are
shown:
(1) All safety and effectiveness data
and information.
(2) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets
and confidential commercial or financial information in § 20.61 of this chapter.
(3) Adverse reaction reports, product
experience reports, consumer complaints, and other similar data and information, after deletion of:
(i) Names and any information that
would identify the person using the
product.
(ii) Names and any information that
would identify any third party involved
with the report, such as a physician or
hospital or other institution.
(4) A list of all active ingredients and
any inactive ingredients previously
disclosed to the public, as defined in
§ 20.81 of this chapter.
(5) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and it is
shown to fall within the exemption established in § 20.61 of this chapter.
(6) All correspondence and written
summaries of oral discussions relating
to the biological product file, in accordance with the provisions of part 20
of this chapter.
(7) All records showing the manufacturer’s testing of a particular lot, after
deletion of data or information that
would show the volume of the drug produced, manufacturing procedures and
controls, yield from raw materials,
costs, or other material falling within
§ 20.61 of this chapter.
(8) All records showing the testing of
and action on a particular lot by the
Food and Drug Administration.
(f) The following data and information in a biological product file are not
available for public disclosure unless
they have been previously disclosed to
the public as defined in § 20.81 of this
chapter or they relate to a product or
ingredient that has been abandoned
and they no longer represent a trade
secret or confidential commercial or financial information as defined in § 20.61
of this chapter:

[39 FR 44656, Dec. 24, 1974, as amended at 42
FR 15676, Mar. 22, 1977; 49 FR 23833, June 8,
1984; 55 FR 11013, Mar. 26, 1990; 61 FR 51530,
Oct. 2, 1996; 64 FR 56452, Oct. 20, 1999; 68 FR
24879, May 9, 2003; 69 FR 13717, Mar. 24, 2004;
70 FR 14984, Mar. 24, 2005]

Subpart G—Postmarketing Studies
SOURCE: 65 FR 64618, Oct. 30, 2000, unless
otherwise noted.

§ 601.70 Annual progress reports of
postmarketing studies.
(a) General requirements. This section
applies to all required postmarketing
studies (e.g., accelerated approval clinical benefit studies, pediatric studies)
and postmarketing studies that an applicant has committed, in writing, to
conduct either at the time of approval
of an application or a supplement to an
application, or after approval of an application or a supplement. Postmarketing studies within the meaning
of this section are those that concern:
(1) Clinical safety;
(2) Clinical efficacy;
(3) Clinical pharmacology; and
(4) Nonclinical toxicology.
(b)What to report. Each applicant of a
licensed biological product shall submit a report to FDA on the status of
postmarketing studies for each approved product application. The status
of these postmarketing studies shall be
reported annually until FDA notifies
the applicant, in writing, that the

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§ 601.70

21 CFR Ch. I (4–1–06 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

agency concurs with the applicant’s determination that the study commitment has been fulfilled, or that the
study is either no longer feasible or
would no longer provide useful information. Each annual progress report
shall be accompanied by a completed
transmittal Form FDA–2252, and shall
include all the information required
under this section that the applicant
received or otherwise obtained during
the annual reporting interval which
ends on the U.S. anniversary date. The
report must provide the following information for each postmarketing
study:
(1) Applicant’s name.
(2) Product name. Include the approved product’s proper name and the
proprietary name, if any.
(3) Biologics license application (BLA)
and supplement number.
(4) Date of U.S. approval of BLA.
(5) Date of postmarketing study commitment.
(6) Description of postmarketing study
commitment. The description must include sufficient information to uniquely describe the study. This information
may include the purpose of the study,
the type of study, the patient population addressed by the study and the
indication(s) and dosage(s) that are to
be studied.
(7) Schedule for completion and reporting of the postmarketing study commitment. The schedule should include the
actual or projected dates for submission of the study protocol to FDA,
completion of patient accrual or initiation of an animal study, completion of
the study, submission of the final
study report to FDA, and any additional milestones or submissions for
which projected dates were specified as
part of the commitment. In addition, it
should include a revised schedule, as
appropriate. If the schedule has been
previously revised, provide both the
original schedule and the most recent,
previously submitted revision.
(8) Current status of the postmarketing
study commitment. The status of each
postmarketing study should be categorized using one of the following
terms that describes the study’s status
on the anniversary date of U.S. approval of the application or other
agreed upon date:

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Food and Drug Administration, HHS

§ 601.91

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.

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

[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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