[Federal Register Volume 77, Number 34 (Tuesday, February 21, 2012)]
[Notices]
[Pages 9946-9947]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3958]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2006-D-0036] (Formerly Docket No. 2006D-0344)


Draft Guidance for Industry on Drug Interaction Studies--Study 
Design, Data Analysis, Implications for Dosing, and Labeling 
Recommendations; 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availability of a revised draft guidance for industry entitled ``Drug 
Interaction Studies--Study Design, Data Analysis, Implications for 
Dosing, and Labeling Recommendations.'' The revised draft guidance is 
intended to provide recommendations for sponsors of new drug 
applications (NDAs) and biologics license applications (BLAs) for 
therapeutic biologics regarding in vitro and in vivo studies of drug 
metabolism, drug transport, and drug-drug, or drug-therapeutic protein 
interactions.

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 
revised draft guidance before it begins work on the final version of 
the guidance, submit either electronic or written comments on the draft 
guidance by May 21, 2012.

ADDRESSES: Submit written requests for single copies of the revised 
draft guidance to the Division of Drug Information, Center for Drug 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. 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    Submit electronic comments on the draft guidance to http://www.regulations.gov.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:
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
Lei Zhang, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 3106, Silver 
Spring, MD 20993-0002, 301-796-1635.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Drug Interaction Studies--Study Design, Data 
Analysis, Implications for Dosing, and Labeling Recommendations.'' Drug 
interactions can result when one drug alters the pharmacokinetics of 
another drug or its metabolites. Drug interactions also can reflect the 
additive nature of the pharmacodynamic effect of either drug when taken 
with the other drug. The main focus of this draft guidance is 
pharmacokinetic drug interactions. The revised draft guidance reflects 
the Agency's view that the pharmacokinetic interactions between an 
investigational new drug and other drugs should be defined during drug 
development, as part of an adequate assessment of safety and 
effectiveness. It is important to understand the nature and magnitude 
of drug-drug interactions for several reasons. Concomitant medications, 
dietary supplements, and some foods, such as grapefruit juice, may 
alter metabolism and/or drug transport abruptly in individuals who 
previously had been receiving and tolerating a particular dose of a 
drug. Such an abrupt alteration in metabolism or transport can change 
the known safety and efficacy of a drug.
    The revised draft guidance provides recommendations for sponsors of 
NDAs and BLAs regarding in vitro and in vivo studies of drug 
metabolism, drug transport, and drug-drug, or drug-therapeutic protein 
interactions. Namely, the guidance describes in vitro study 
methodologies, criteria for in vivo studies, in vivo study design, and 
data analysis in the context of identifying potential drug 
interactions. The guidance also addresses the implications of drug 
interactions for dosing and labeling.
    In the Federal Register of September 12, 2006 (71 FR 53696), FDA 
announced the availability of a draft guidance entitled ``Drug 
Interaction Studies--Study Design, Data Analysis, and Implications for 
Dosing and Labeling.'' Comments were received and have been considered 
during revision of the draft guidance. In addition, new developments in 
the field have been incorporated to reflect the Agency's current 
thinking. The Agency is publishing the draft guidance as a revised 
draft guidance to collect additional public comments. The revised draft 
guidance includes detailed discussion of several major changes, 
including the following: (1) When transporter-mediated drug interaction 
information is needed (including decision-trees); (2) drug-therapeutic 
protein interactions, (3) the utility of pharmacogenetic data; and (4) 
the use of physiologically based pharmacokinetic modeling.
    This revised draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The draft guidance, 
when

[[Page 9947]]

finalized, will represent the Agency's current thinking on conducting 
drug interaction studies during drug development to support marketing 
approval. 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 revised 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. 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.regulations.gov.

    Dated: February 15, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-3958 Filed 2-17-12; 8:45 am]
BILLING CODE 4160-01-P