[Federal Register: September 8, 1999 (Volume 64, Number 173)]
[Notices]
[Page 48842-48843]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08se99-75]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 97D-0433]


Draft Guidance for Industry on Average, Population, and
Individual Approaches to Establishing Bioequivalence; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Average,
Population, and Individual Approaches to Establishing Bioequivalence.''
This draft guidance provides recommendations to sponsors and/or
applicants intending to perform in vivo and in vitro bioequivalence
(BE) studies based on comparisons of in vivo and in vitro

[[Page 48843]]

bioavailability (BA) measures in investigational new drug applications,
new drug applications, abbreviated new drug applications, and their
amendments and supplements. This draft guidance is a modification of a
preliminary draft guidance entitled ``In Vivo Bioequivalence Studies
Based on Population and Individual Bioequivalence Approaches''
published in December 1997, and this draft guidance updates a July 1992
FDA guidance entitled ``Statistical Procedures for Bioequivalence
Studies Using a Standard Two-Treatment Crossover Design''. When
finalized, this draft guidance will replace both the 1992 and 1997
guidances.

DATES: Written comments may be submitted on the draft guidance document
by November 8, 1999. General comments on agency guidance documents are
welcome at any time.

ADDRESSES: Copies of this draft guidance for industry are available on
the Internet at ``http://www.fda.gov/cder/guidance/index.htm''. Submit
written requests for single copies of ``Average, Population, and
Individual Approaches to Establishing Bioequivalence'' to the Drug
Information Branch (HFD-210), Center for Drug Evaluation and Research,
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
Send one self-addressed adhesive label to assist that office in
processing your requests. Submit written comments on the draft guidance
to the Dockets Management Branch (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Mei-Ling Chen, Center for Drug
Evaluation and Research (HFD-870), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-5919.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a
draft guidance for industry entitled ``Average, Population, and
Individual Approaches to Establishing Bioequivalence.'' The draft
guidance provides recommendations to sponsors and/or applicants
intending to perform in vivo and in vitro BE studies based on
comparisons of in vivo and in vitro BA measurements. In an earlier
guidance entitled ``Statistical Procedures for Bioequivalence Studies
Using a Standard Two-Treatment Crossover Design,'' FDA recommended that
an average BE approach be used to establish BE between test and
reference drug products. Because of the limitations in the average BE
approach, and after extensive intramural and extramural discussions,
the Center for Drug Evaluation and Research (CDER) now recommends that
the average BE approach be supplemented by two new approaches,
population and individual BE. This draft guidance focuses on how to use
each approach once a specific criterion has been chosen.
    This draft guidance is one of a set of seven core guidances being
developed to provide recommendations on how to meet provisions of part
320 (21 CFR part 320) for orally administered drug products and drug
products for local action. Taken together, the seven guidances are
designed to clarify the studies needed to document product quality BA/
BE for all drug products regulated by CDER in accordance with the
provisions in part 320. A further intent is to reduce regulatory burden
where feasible.
    This level 1 draft guidance is being issued consistent with FDA's
good guidance practices (62 FR 8961, February 2, 1997). It represents
the agency's current thinking on average, population, and individual
approaches to establishing BE. It does not create or confer any rights
for or on any person and does not operate to bind FDA or the public. An
alternative approach may be used if such an approach satisfies the
requirements of the applicable statutes, regulations, or both.
    Interested persons may, at any time, submit written comments on the
draft guidance to the Dockets Management Branch (address above). Two
copies of any comments are to be submitted, except that individuals may
submit one copy. Comments are to be identified with the docket number
found in brackets in the heading of this document. A copy of the draft
guidance and received comments are available for public examination in
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through
Friday.

    Dated: August 26, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-23228 Filed 9-7-99; 8:45 am]
BILLING CODE 4160-01-F