[Federal Register Volume 66, Number 23 (Friday, February 2, 2001)]
[Notices]
[Pages 8805-8806]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-2789]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01D-0027]


Guidance for Industry on Statistical 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 guidance for industry entitled ``Statistical 
Approaches to Establishing Bioequivalence.'' This guidance provides 
recommendations to sponsors and/or applicants who intend to use 
equivalence criteria in analyzing in vivo or in vitro bioequivalence 
(BE) studies for investigational new drug applications (IND's), new 
drug applications (NDA's), abbreviated new drug applications (ANDA's) 
and supplements to these applications. The guidance discusses the use 
of average, population, and individual BE approaches to compare in vivo 
and in vitro bioavailability (BA) measures. (This guidance replaces the 
draft guidance that was issued in 1999 entitled ``Average, Population, 
and Individual Approaches to Establishing Bioequivalence.'')

DATES: Submit written comments on agency guidances at any time.

ADDRESSES: Copies of this guidance for industry are available on the 
Internet at http://www.fda.gov/cder/guidance/index.htm. Submit written 
requests for single copies of this guidance 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 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-350), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-5688.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a 
guidance for industry entitled ``Statistical Approaches to Establishing 
Bioequivalence.'' This guidance provides information on statistical 
approaches for sponsors and/or applicants intending to provide BA and 
BE information to the agency in IND's, NDA's, ANDA's, and their 
supplements.
    Over the years, BA/BE data have been analyzed using an average BE 
approach. This statistical guidance describes two new approaches for 
analysis, population and individual BE. This guidance does not provide 
information about when an approach should be used; that information is 
provided in other FDA BA/BE guidances. Instead, the guidance provides 
recommendations on how to use each of these approaches once one has 
been selected.
    This guidance is a final revision of a document that began with the 
publication of a preliminary draft guidance on this subject entitled 
``In Vivo Bioequivalence Studies Based on Population and Individual 
Bioequivalence Approaches'' in 1997 (62 FR 67880, December 30, 1997), 
and was followed by a draft guidance entitled ``Average, Population, 
and Individual Approaches to Establishing Bioequivalence,'' published 
in 1999 (64 FR 48842, September 8, 1999). This final guidance replaces 
both of these draft guidances and a 1992 FDA guidance entitled 
``Statistical Procedure for Bioequivalence Studies Using a Standard 
Two-Treatment Crossover Design.''
    In September 1999, FDA announced the availability of a draft 
guidance entitled ``BA and BE Studies for Orally Administered Drug 
Products--General Considerations'' (64 FR 48409, September 3, 1999). 
That draft guidance was intended to provide general information on how 
to comply with the BA and BE requirements in part 320 (21 CFR part 320) 
for orally administered dosage forms. When that draft guidance was 
published, FDA received a total of 16 public comments, a number of 
which

[[Page 8806]]

expressed concern about the use of the individual BE approach.
    FDA acknowledged the public concerns about the use of the 
individual BE approach when the final guidance entitled ``BA and BE 
Studies for Orally Administered Drug Products--General Considerations'' 
(65 FR 64449, October 27, 2000) was issued. In that guidance, FDA 
recommends the continued use of the average BE approach for both 
replicated and nonreplicated studies. However, that guidance states 
that sponsors have the option to choose another approach, e.g., an 
individual BE approach for highly variable drugs. The final statistical 
guidance being made available today provides recommendations on how to 
use this approach if it is chosen.
    This statistical guidance is one of a set of core guidances being 
developed to provide recommendations on how to meet the provisions of 
part 320. Taken together, these guidances are designed to address the 
studies that should be provided to document product quality BA/BE for 
all drug products regulated by CDER in accordance with the provisions 
of part 320.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (65 FR 56468, September 19, 2000). This Level 1 
guidance document represents the agency's current thinking on the 
statistical approaches used in BA and BE studies. 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 
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. The guidance and received 
comments are available for public examination in the Documents 
Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: January 24, 2001.
Ann M. Witt,
Acting Associate Commissioner for Policy.
[FR Doc. 01-2789 Filed 2-1-01; 8:45 am]
BILLING CODE 4160-01-S