[Federal Register Volume 78, Number 18 (Monday, January 28, 2013)]
[Notices]
[Pages 5816-5817]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-01638]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Guidance for Industry on Clinical Pharmacogenomics: Premarket 
Evaluation in Early-Phase Clinical Studies and Recommendations for 
Labeling; 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 ``Clinical 
Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies 
and Recommendations for Labeling.'' This guidance is intended to assist 
the pharmaceutical industry and other investigators engaged in new drug 
development in evaluating how variations in the human genome, 
specifically DNA sequence variants, could affect a drug's 
pharmacokinetics (PK), pharmacodynamics (PD), efficacy, or safety. The 
guidance provides recommendations on when and how genomic principles 
should be considered and applied in early-phase clinical studies to 
address questions arising during drug development and regulatory 
review.

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

ADDRESSES: Submit written requests for single copies of this 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, Rockville, MD 20852-1448. The guidance may also be 
obtained by mail by calling CBER at 1-800-835-4709 or 301-827-1800. 
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 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: Issam Zineh, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 3178, Silver Spring, MD 20993-0002, 301-
796-4756; or Stephen Ripley, Center for Biologics Evaluation and 
Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, 
suite 200N, Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance entitled 
``Clinical Pharmacogenomics: Premarket

[[Page 5817]]

Evaluation in Early-Phase Clinical Studies and Recommendations for 
Labeling.'' This guidance should help sponsors, researchers, and other 
interested persons engaged in new drug development in evaluating how 
variations in the human genome, specifically DNA sequence variants, 
could affect a drug's pharmacokinetics, pharmacodynamics, efficacy, or 
safety. The guidance provides recommendations on when and how genomic 
principles should be considered and applied in early-phase clinical 
studies to address questions arising during drug development and 
regulatory review. The guidance does not address trial design or 
statistical analysis considerations for later-phase randomized 
controlled clinical trials that are intended to draw definitive 
conclusions about treatment effects in a genomic subgroup or 
codevelopment of a drug and in vitro diagnostic. Rather, the 
considerations here are more relevant for exploratory and observational 
studies intended to generate genomic hypotheses that may then be tested 
in confirmatory trials.
    Drug development is commonly described in ``phases'' (21 CFR 
312.21). The first two phases provide initial information about safety 
and efficacy, and ideally examine a broad range of doses, so that the 
larger, later adequate, and well-controlled trials (phase 3) that are 
needed to support marketing approval can be efficiently designed. 
Across the drug development continuum, genomic data may be used for 
several purposes, including: (1) Identifying the basis for PK outliers 
and intersubject variability in clinical response; (2) ruling out the 
role of polymorphic pathways as clinically significant contributors to 
variable PK, PD, efficacy, or safety; (3) estimating the magnitude of 
potential drug-drug interactions; (4) investigating the molecular or 
mechanistic basis for lack of efficacy or occurrence of adverse 
reactions; and (5) designing clinical trials to test for greater 
effects in specific subgroups (i.e., use in study enrichment 
strategies).
    On February 18, 2011 (76 FR 9583), FDA issued a draft of this 
guidance to solicit comments from the public. After carefully reviewing 
received comments and in light of increased regulatory experience and 
the evolution of the science, FDA has revised the guidance. In addition 
to making clarifying changes, FDA added content to describe when 
pharmacogenomics (PGx) studies are warranted, including circumstances 
when full sample ascertainment is expected to evaluate a specific 
hypothesis. In addition, a number of topics were further elaborated, 
including targeted sample collection, sample retention, genotyping 
approaches, pooled analyses, dedicated prospective PGx studies, genetic 
substudies, and safety PGx.
    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 conducting pharmacogenomic studies in 
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 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 have been approved under OMB 
control numbers 0910-0014 and 0910-0572.

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of 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, and will be posted to the docket at http://www.regulations.gov.

IV. Electronic Access

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

    Dated: January 22, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-01638 Filed 1-25-13; 8:45 am]
BILLING CODE 4160-01-P