[Federal Register Volume 76, Number 34 (Friday, February 18, 2011)]
[Notices]
[Pages 9583-9584]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-3679]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0082]


Draft Guidance for Industry on Clinical Pharmacogenomics: 
Premarketing Evaluation in Early Phase Clinical 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availability of a draft guidance for industry entitled ``Clinical 
Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical 
Studies.'' The draft guidance is intended to assist the pharmaceutical 
industry and other investigators engaged in new drug development in 
evaluating how variations in the human genome could affect the clinical 
pharmacology properties and clinical responses of drugs.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by April 19, 2011.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002 or the 
Office of Communication, Outreach and Development (HFM-40), Center for 
Biologics Evaluation and Research (CBER), Food and Drug Administration, 
1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Lawrence J. Lesko, Center for Drug Evaluation and Research, Food and 
Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 3178, 
Silver Spring, MD 20993-0002, 301-796-1565; or
Shiew-Mei Huang, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 3188, Silver 
Spring, MD 20993-0002, 301-796-1541; or
Stephen Ripley, Center for Biologics Evaluation and Research, Food and 
Drug Administration (HFM-17), 1401 Rockville Pike, suite 200N, 
Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance entitled 
``Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase 
Clinical Studies.'' Pharmacogenomics (PGx) broadly refers to the study 
of variations of DNA and RNA characteristics and their relation to drug 
exposure and/or response. Drug exposure refers to either the 
administered dose or levels in a body tissue or fluid (e.g., blood, 
plasma, cerebrospinal fluid). Drug response results from the interplay 
of pharmacokinetics (e.g., drug absorption, metabolism, and excretion), 
and pharmacodynamics (i.e., all of the effects of the drug on various 
physiologic and pathologic processes, including effectiveness and 
adverse effects). Genetic variations can also influence the exposure-
response (E/R) relationship of drugs. PGx studies can enhance the 
understanding of interindividual differences in the efficacy and safety 
of investigational drugs.
    Drug development is commonly described as going through ``phases'' 
(21 CFR 312.21). The first two phases collect information about safety 
and dosing, so that the larger, later (phase 3) studies (the adequate 
and well-controlled studies needed to support marketing approval) can 
gather the additional information about effectiveness and safety that 
is needed to evaluate the overall benefit-risk relationship of the drug 
and to provide an adequate basis for physician labeling. Much of the 
genomic information collected and assessed during the early phases is 
often described as ``exploratory.'' Phase 2 studies that suggest 
genomic influences can lead to phase 3 trials that incorporate findings 
into prespecified hypotheses, such as enriching the study with 
genomically defined individuals, determining dose based on demonstrated 
variability in earlier studies, and defining a priori hypothesis 
testing of a primary endpoint in a genomic subset.
    PGx information obtained from genomic investigations during the 
course of drug development (and from postmarketing studies) can improve 
the effectiveness and safety of drugs by identifying patients at high 
risk for a serious adverse event or absence of benefit; improving the 
benefit/risk relationship of drugs by using genomic tests to identify 
patients most likely to respond, or unable to respond to a drug; and by 
helping to select optimal doses based on genotype-driven differences in 
PK (pharmacodynamics) and/or PD (pharmacodynamics) of a drug. An 
important prerequisite to successful use of genetic information in drug 
development is appropriate collection and storage of DNA samples from 
all clinical trials, both exploratory and the adequate and well-
controlled studies intended to support effectiveness and safety.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance 
represents the Agency's current thinking on conducting pharmacogenomic 
studies in

[[Page 9584]]

early phase clinical studies. 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 
requirement of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR 201.57 have been 
approved under OMB control number 0910-0572.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments 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.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances, or http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances, or http://www.regulations.gov.

    Dated: February 14, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-3679 Filed 2-17-11; 8:45 am]
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