[Federal Register Volume 64, Number 173 (Wednesday, September 8, 1999)]
[Notices]
[Pages 48842-48843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-23228]


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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Draft Guidance for Industry on Average, Population, and 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availability of a draft guidance for industry entitled ``Average, 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This draft guidance provides recommendations to sponsors and/or 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 This draft guidance is a modification of a 
preliminary draft guidance entitled ``In Vivo Bioequivalence Studies 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published in December 1997, and this draft guidance updates a July 1992 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finalized, this draft guidance will replace both the 1992 and 1997 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DATES: Written comments may be submitted on the draft guidance document 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ADDRESSES: Copies of this draft guidance for industry are available on 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 Submit written comments on the draft guidance 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]
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