[Federal Register Volume 71, Number 2 (Wednesday, January 4, 2006)]
[Notices]
[Pages 350-351]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E5-8224]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D-0493]


Guidance for Industry and Review Staff on Recommended Approaches 
to Integration of Genetic Toxicology Study Results; 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

[[Page 351]]

and review staff entitled ``Recommended Approaches to Integration of 
Genetic Toxicology Study Results.'' This guidance is intended to inform 
industry and the review staff in the Center for Drug Evaluation and 
Research (CDER) on how CDER views positive findings in genetic 
toxicology assays during drug development. The guidance provides 
recommendations on how to proceed with clinical studies while ensuring 
the safety of study participants when results in genotoxicity studies 
suggest a potential cancer or genetic hazard.

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.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: David Jacobson-Kram, Center for Drug 
Evaluation and Research (6411), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 6488, Silver Spring, MD 20993, 301-796-
0175.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry and 
review staff entitled ``Recommended Approaches to Integration of 
Genetic Toxicology Study Results.'' Pharmaceuticals administered 
through oral, intravenous, topical, and other routes, as appropriate, 
are subject to this guidance.
    In the Federal Register of December 2, 2004 (69 FR 70153), FDA 
announced the availability of a draft version of the guidance entitled 
``Recommended Approaches to Integration of Genetic Toxicology Study 
Results.'' When the draft guidance was published, FDA requested 
comments on the document. Some changes were made to the draft document 
based on comments submitted to the docket including the following 
changes: (1) The guidance now suggests that for a compound giving 
positive results in a genetic toxicology assay, an alternative to 
demonstrating ``mechanism of action'' would be ruling out mechanisms 
involving direct interaction with dexoyribonucleic acid (DNA) and (2) 
alkaline elution is included as an example of an assay for measuring 
DNA damage. Other editorial changes were also made.
    A number of comments to the docket suggested that the fourth test 
in the International Conference on Harmonisation (ICH) battery should 
be an option for compounds giving a positive response in one of the 
initial assays. This change was not included. Positive responses are 
primarily seen in the in vitro chromosomal aberration assay and/or the 
mouse lymphoma assay. Because these two tests measure common genetic 
lesions and have similar drug exposure protocols, the data from the two 
assays can be used to corroborate results.
    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 recommended approaches to integration of 
genetic toxicology study results. 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 on the guidance at any 
time. 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. The guidance and 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: December 21, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E5-8224 Filed 1-3-06; 8:45 am]
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