Draft Guidance for Industry on Topical Dermatological Drug Product NDA's and ANDA'sIn Vivo Bioavailability, Bioequivalence, In Vitro Release and Associated Studies; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D-0388]

Draft Guidance for Industry on Topical Dermatological Drug

Product NDA's and ANDA's--In Vivo Bioavailability, Bioequivalence, In

Vitro Release and Associated Studies; 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availability of a draft guidance for industry entitled ``Topical

Dermatological Drug Product NDA's and ANDA's--In Vivo Bioavailability,

Bioequivalence, In Vitro Release and Associated Studies.'' The draft

guidance is intended to provide recommendations to sponsors of new drug

applications (NDA's), abbreviated new drug applications (ANDA's), and

supplements who intend to perform bioavailability and bioequivalence

studies for topically applied dermatological drug products during

either the preapproval or postapproval period. The agency is seeking

comments on the draft guidance.

DATES: Written comments may be submitted on the draft guidance by

August 17, 1998. General comments on the agency guidances are welcome

at any time.

ADDRESSES: Copies of this draft guidance are available on the Internet

at ``http://www.fda.gov/cder/guidance/index.htm'' .

Submit written comments on this draft guidance to the Dockets

Management Branch (HFD-305), Food and Drug Administration, 12420

Parklawn Dr., rm 1-23, Rockville, MD. 20857. 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.

FOR FURTHER INFORMATION CONTACT: Vinod P. Shah, Center for Drug

Evaluation and Research (HFD-350), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-594-5635.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a

draft guidance for industry entitled ``Topical Dermatological Drug

Product NDA's and ANDA's--In Vivo Bioavailability, Bioequivalence, In

Vitro Release and Associated Studies.'' The draft guidance

[[Page 33376]]

is intended to provide recommendations to sponsors of NDA's, ANDA's,

and supplements who intend to perform, during either the preapproval or

postapproval period, bioavailability and bioequivalence studies for

topical dermatological drug products.

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 CFR part

320. These regulatory definitions and requirements reflect requirements

in the Federal Food, Drug, and Cosmetic Act and other agency

regulations.

Generally, bioavailability and bioequivalence of a drug product can

be assessed through measurement of the active moiety(ies)/active

ingredient(s) in an accessible biologic fluid such as blood, plasma,

and urine. For some drug products, including topical dermatological

drug products, it is not possible to use pharmacokinetic measurements

of the active moiety(ies)/active ingredient(s) in blood, plasma, or

urine to document bioequivalence because topical dermatological

products generally do not produce measurable concentrations in

extracutaneous biological fluids. This draft guidance document proposes

other methods to establish bioavailability and bioequivalence,

including the following types of studies: (1) Clinical studies; (2)

pharmacodynamic studies; (3) dermatopharmacokinetic studies; and (4) in

vitro studies. These approaches are discussed at 21 CFR 320.24,

although these regulations do not provide specific methodologic

approaches. In addition to general comments, FDA welcomes the

submission of data that support or refute the use of any of these

approaches, especially dermatopharmacokinetic approaches, in the

documentation of bioavailiability and bioequivalence of topical

dermatological drug products. FDA also welcomes the submission of

relevant clinical, dermatopharmacokinetic, and in vitro release data

for further evaluation of these approaches in the guidance. At some

time following receipt of public comments and other information to this

draft guidance, FDA intends to discuss the guidance and the public

response to the guidance before a joint meeting of the Advisory

Committee for Pharmaceutical Science and the Dermatologic and

Ophthalmic Drugs Advisory Committee.

This draft guidance is a level 1 draft guidance document consistent

with FDA's good guidance practices (62 FR 8961, February 27, 1997). It

represents the agency's current thinking on bioavailability and

bioequivalence approaches for topical dermatological drug products. 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.

Submit written requests for single copies of the draft 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. Requests should be identified with the

docket number found in brackets in the heading of this document. Copies

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: June 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-16141 Filed 6-17-98; 8:45 am]

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