[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Draft Guidance for Industry on Safety Testing of Drug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availability of a draft guidance for industry entitled ``Safety Testing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 This draft guidance provides recommendations on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draft guidance is intended to serve as a resource for general testing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DATES: Submit written or electronic comments on the draft guidance by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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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on the draft guidance to the Division of Dockets Management (HFA-305),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access to the draft guidance document.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FDA is announcing the availability of a draft guidance for industry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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