Document Headings

                    Document headings vary by document type but may contain                    the following:                  
                -                       the agency or agencies that issued and signed a document                    
                -                       the number of the CFR title and the number of each part                      the document amends, proposes to amend, or is directly                      related to                    
                -                       the agency docket number / agency internal file number                    
                -                       the RIN which identifies each regulatory action listed in                      the Unified Agenda of Federal Regulatory and Deregulatory                      Actions                    

                    See the                                          Document Drafting Handbook                                        for more details.                  

###### Department of Health and Human Services

###### Food and Drug Administration

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

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# 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The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies.” The draft guidance is intended to assist the pharmaceutical industry and other investigators engaged in new drug development in evaluating how variations in the human genome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any time (                        *see*21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by April 19, 2011.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                        Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201,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                           ( print 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]

BILLING CODE 4160-01-P