[Federal Register Volume 67, Number 152 (Wednesday, August 7, 2002)]
[Notices]
[Pages 51284-51285]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-19863]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02D-0307]


Draft Guidance for Industry on Potassium Chloride Modified-
Release Tablets and Capsules: In Vivo Bioequivalence and In Vitro 
Dissolution Testing, Revision; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration is announcing the 
availability of a revised draft guidance for industry entitled 
``Potassium Chloride Modified-Release Tablets and Capsules: In Vivo 
Bioequivalence and In Vitro Dissolution Testing.'' This draft guidance 
document provides recommendations to sponsors of abbreviated new drug 
applications (ANDAs) on the design of bioequivalence studies for 
modified-release dosage forms of potassium chloride.

DATES: Submit written or electronic comments on the draft guidance by 
September 23, 2002. General comments on agency guidance documents are 
welcome at any time.

[[Page 51285]]


ADDRESSES: Submit written requests for single copies of this draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Dockets Management Branch (HFA-305), Food 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 
20857. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Lizzie Sanchez, Center for Drug 
Evaluation and Research (HFD-650), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-5847.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Potassium Chloride Modified-Release Tablets and 
Capsules: In Vivo Bioequivalence and In Vitro Dissolution Testing.'' 
This draft guidance is intended to provide information to sponsors of 
ANDAs on the design of bioequivalence studies for modified-release 
dosage forms of potassium chloride. A document entitled ``Guidance for 
In Vivo Bioequivalence Study for Slow-Release Potassium Chloride 
Tablets/Capsules'' was issued on May 15, 1987, and revised on June 6, 
1994. The guidance is now being revised to incorporate current thinking 
on the bioequivalence requirements for potassium chloride modified-
release products.
    In the previous guidance, the agency recommended a three-way 
crossover study design comparing the reference product (RLD) to the 
generic product and to a solution of potassium chloride. The earlier 
guidance also recommended analysis of covariance (ANCOVA) for the 
pharmacokinetic parameters. The revised draft guidance provides 
recommendations for a two-way crossover study design comparing the 
generic product to the RLD. In addition, in the revision, the use of 
ANCOVA is no longer recommended. The agency has found that the analysis 
of variance (ANOVA) with baseline correction is adequate for 
bioequivalence analysis of pharmacokinetic data obtained following oral 
administration of potassium chloride drug products. The recommendations 
for in vitro dissolution testing and the criteria for waivers of in 
vivo testing for lower strengths have been revised in accordance with 
the guidance entitled ``Bioavailability and Bioequivalence Studies for 
Orally Administered Drug Products--General Considerations,'' issued in 
October 2000.
    The agency is issuing this product-specific draft guidance because 
of special considerations for potassium chloride testing that are not 
covered in other agency guidances.
    This revised draft guidance is being issued consistent with FDA's 
good guidance practices (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on studies to 
demonstrate the bioequivalence of potassium chloride modified-release 
tablets and capsules. 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 
applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic comments on the draft guidance. 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 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.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: July 31, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-19863 Filed 8-6-02; 8:45 am]
BILLING CODE 4160-01-S