[Federal Register Volume 70, Number 107 (Monday, June 6, 2005)]
[Notices]
[Page 32839]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-11205]



[[Page 32839]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0203]


Draft Guidance for Industry on Safety Testing of Drug 
Metabolites; 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availability of a draft guidance for industry entitled ``Safety Testing 
of Drug Metabolites.'' This draft guidance provides recommendations on 
the safety assessment of unique or major human metabolites of small 
molecule (nonbiologic) therapeutic products under development. This 
draft guidance is intended to serve as a resource for general testing 
considerations as well as provide recommendations on the timing of 
these studies in relation to the clinical development.

DATES: Submit written or electronic comments on the draft guidance by 
August 5, 2005. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Division of Dockets Management (HFA-305), 
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852. 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access to the draft guidance document.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: Aisar Atrakchi, Center for Drug 
Evaluation and Research (HFD-120), Food and Drug Administration, 1451 
Rockville Pike, Rockville, MD 20852, 301-594-2850.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Safety Testing of Drug Metabolites.'' There are quantitative 
and qualitative differences in metabolic profiles across species. These 
differences become important when exposure parameters of a drug in a 
nonclinical species are used to assess safety in humans during risk 
assessment. In the past, contribution of metabolites to the overall 
toxicological potential of the parent drug was generally unknown or not 
considered; analytical technologies to identify and measure metabolites 
have only become available over the past decade.
    Although in general there is adequate correlation in metabolic 
profiles between humans and those obtained in standard nonclinical 
safety studies, there are, however, cases when these studies do not 
adequately evaluate clinically relevant and/or biologically active 
metabolites. This may be due to such metabolites being unique to humans 
or present at very low levels in the animal species used in the 
standard toxicity studies. As a result, FDA has developed a draft 
guidance to provide recommendations on the safety assessment of unique 
or major human metabolites of small molecule (nonbiologic) therapeutic 
products. These recommendations should help applicants conduct adequate 
safety assessments of metabolites.
    This draft guidance provides general testing considerations for 
unique or major drug metabolites including study design, identification 
of metabolites, structure activity relationship, and types of 
nonclinical studies needed to assess metabolite toxicity. It also 
addresses the timing of these studies in relation to the clinical 
development.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on safety 
testing of drug metabolites. 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 statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management 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: May 27, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-11205 Filed 6-3-05; 8:45 am]
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