[Federal Register Volume 62, Number 249 (Tuesday, December 30, 1997)]
[Notices]
[Pages 67880-67881]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-33795]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 97D-0433]
Preliminary Draft Guidance for Industry on In Vivo Bioequivalence
Studies Based on Population and Individual Bioequivalence Approaches;
Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a preliminary draft guidance for industry entitled ``In
Vivo Bioequivalence Studies Based on Population and Individual
Bioequivalence Approaches.'' If this preliminary draft guidance becomes
final, it will provide recommendations to sponsors of investigational
new drug applications (IND's), new drug applications (NDA's),
abbreviated new drug applications (ANDA's), and abbreviated antibiotic
drug applications (AADA's) who intend to perform studies based on a
comparison of pharmacokinetic metrics. If finalized, the guidance would
replace a prior guidance entitled ``Statistical Procedures for
Bioequivalence Studies Using a Standard Two-Treatment Crossover
Design,'' which was published in July 1992. Because a transition to the
approaches delineated in this document will require careful
consideration, FDA is making it available as a preliminary draft.
DATES: Written comments may be submitted on the preliminary draft
guidance document by March 2, 1998. General comments on agency guidance
documents are welcome at any time.
ADDRESSES: Copies of this preliminary draft guidance are available on
the Internet at ``http://www.fda.gov/cder/guidance/index.htm.'' Written
requests for single copies of the preliminary draft guidance for
industry should be submitted 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Submit written comments on the preliminary draft guidance to the
Dockets Management Branch (HFD-305), Food and Drug Administration,
12420 Parklawn Dr., rm 1-23, Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT:
Mei-Ling Chen, Office of Clinical Pharmacology and
Biopharmaceutics, Center for Drug Evaluation and Research (HFD-870),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
301-827-5919, or
Rabindra N. Patnaik, Office of Generic Drugs, Center for Drug
Evaluation and Research (HFD-651), 7500 Standish Pl., Food and Drug
Administration, Rockville, MD 20855, 301-827-5847.
SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a
preliminary draft guidance for industry entitled ``In Vivo
Bioequivalence Studies Based on Population and Individual
Bioequivalence Approaches.'' If it becomes final, this guidance for
industry will provide recommendations to sponsors of IND's, NDA's,
ANDA's, and AADA's who intend to perform in vivo bioequivalence studies
based on a comparison of pharmacokinetic metrics, either prior to or
following approval.
The definitions of ``bioavailability'' and ``bioequivalence;'' the
requirements for submitting such data in NDA's, ANDA's, and
supplements; and the types of in vivo studies that are acceptable to
establish bioavailability and bioequivalence are set forth in 21 CFR
part 320. These regulatory definitions and requirements reflect
requirements in the Federal Food, Drug, and Cosmetic Act and other
agency regulations.
Bioavailability and bioequivalence are usually measured by in vivo
studies assessing metrics of a plasma or blood concentration-time curve
to establish the rate and extent of absorption of an appropriate active
drug/metabolite (bioavailability), or to compare the rate and extent of
absorption of a test and reference formulation (bioequivalence).
In the July 1992 guidance for industry entitled ``Statistical
Procedures for Bioequivalence Studies Using a Standard Two-Treatment
Crossover Design,'' FDA recommended that a standard in vivo
bioequivalence study design be based on administration of the test and
reference products on separate occasions to healthy subjects, either in
single or multiple doses, with random assignment to the two possible
sequences of drug product administration.
Based on work performed during the last several years by scientists
within and outside FDA, this preliminary draft guidance for industry
recommends that the approach for determining average bioequivalence
discussed in the 1992
[[Page 67881]]
guidance be replaced by two new statistical approaches termed
``population'' and ``individual'' bioequivalence.
In contrast to the standard bioequivalence approach, which focuses
on assessing and comparing only population averages for a
bioavailability metric of interest for a test and reference product,
the population and individual bioequivalence approaches assess and
compare both population averages and population variances for the
metric.
This preliminary draft guidance recommends that the population
bioequivalence approach be used by NDA sponsors who wish to assess
bioequivalence during the investigational phase of drug development.
The preliminary draft guidance recommends that the individual
bioequivalence approach be used by sponsors of ANDA's and AADA's to
assess bioequivalence between a generic and reference listed drug, or
by sponsors of NDA's, ANDA's, and AADA's who, during the postapproval
period, wish to reassess in vivo bioequivalence when a change of
sufficient magnitude occurs in the formulation and/or manufacturing of
the drug product. If finalized, this guidance would replace the 1992
guidance.
Because transition to the approaches delineated in this preliminary
draft will require careful consideration, FDA is publishing it as a
preliminary draft guidance. The agency hopes to engage the public in a
discussion of the justification for and implications of the
recommendations that are presented. This public discussion may include
a number of activities, such as holding a public workshop, creating an
expert panel, and other discussions and deliberations as appropriate.
At the conclusion of this public discussion, which is expected to take
at least several months, FDA may release the draft document for a
second round of public comment. Despite the possibility that the draft
guidance may be released again for comment, the public is encouraged to
comment now on this preliminary version and, specifically, to provide
information that supports or refutes the importance of its proposals.
Given the need for careful consideration of some of the
recommendations in the preliminary draft, FDA does not recommend
implementation of any of its provisions at this time.
This preliminary draft guidance for industry represents the
agency's current thinking on in vivo bioequivalence studies based on
population and individual bioequivalence approaches. 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 approach
satisfies the requirements of the applicable statute, regulations, or
both.
Interested persons may, at any time, submit written comments on the
preliminary 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 preliminary draft guidance and received comments may be seen in
the office above between 9 a.m. and 4 p.m., Monday through Friday.
Dated: December 17, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-33795 Filed 12-29-97; 8:45 am]
BILLING CODE 4160-01-F
