[Federal Register Volume 78, Number 18 (Monday, January 28, 2013)]
[Notices]
[Pages 5816-5817]
From the Federal Register Online via the Government Printing 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