[Federal Register: February 15, 2008 (Volume 73, Number 32)]
[Notices]               
[Page 8884-8885]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15fe08-65]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0065 (formerly Docket No. 2005D-0203)]

 
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 guidance for industry entitled ``Safety Testing of 
Drug Metabolites.'' This guidance provides recommendations to industry 
on when and how to identify and characterize drug metabolites whose 
nonclinical toxicity needs to be evaluated. It also provides 
recommendations on the timing and type of nonclinical studies that 
should be conducted to investigate the potential for clinical toxicity 
of drug metabolites. This guidance applies to small molecule 
nonbiologic drug products under development. This guidance finalizes 
the draft guidance published on June 6, 2005.

DATES: Submit written or electronic comments on agency guidances at any 
time.

ADDRESSES: Submit written requests for single copies of this 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 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.regulations.gov. See 

the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.

FOR FURTHER INFORMATION CONTACT:  Aisar Atrakchi, Center for Drug 
Evaluation and Research (HFD-130), Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 22, rm. 4384, Silver Spring, MD 20993-0002, 
301-796-1036.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Safety Testing of Drug Metabolites.'' This guidance 
addresses drug metabolites of small molecule nonbiologic drug products 
and does not apply to some cancer products. It applies to drug 
metabolites that are not adequately evaluated in standard toxicology 
testing with the parent drug. This can happen if the metabolite is 
present only in humans or if it is present at higher levels (referred 
to in the guidance as ``disproportionate drug metabolite'') in humans 
than in any of the animal toxicology test species. The guidance 
provides recommendations on the timing and types of nonclinical safety

[[Page 8885]]

studies that should be conducted for drug metabolites that are present 
at greater than 10 percent of the parent drug systemic exposure as 
measured in plasma.
    A draft version of this guidance was made available for public 
comment in 2005 (70 FR 32839, June 6, 2005). All of the public comments 
we received have been considered and the guidance was revised as 
appropriate.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
agency's current thinking on the 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 this 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.
    Please note that on January 15, 2008, the FDA Web site transitioned 
to the Federal Dockets Management System (FDMS). FDMS is a Government-
wide, electronic docket management system. Electronic submissions will 
be accepted by FDA through FDMS only.

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: February 8, 2008.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E8-2827 Filed 2-14-08; 8:45 am]

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