[Federal Register Volume 70, Number 16 (Wednesday, January 26, 2005)]
[Notices]
[Pages 3714-3715]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-1394]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0004]


Draft Guidance for Industry on Nonclinical Safety Evaluation of 
Drug Combinations; 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availability of a draft guidance for industry entitled ``Nonclinical 
Safety Evaluation of Drug Combinations.'' The guidance provides 
recommendations on nonclinical approaches to support the clinical study 
and approval of fixed-dose combination products (FDCs), copackaged 
products, and adjunctive therapies.

DATES: Submit written or electronic comments on the draft guidance by 
April 26, 2005. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to 
assist that office in processing your requests. Submit written comments 
on the draft guidance to the Division of Dockets Management (HFA-305), 
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Abby Jacobs, Center for Drug 
Evaluation and Research (HFD-540), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2020.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Nonclinical Safety Evaluation of Drug Combinations.'' Drug 
combinations include FDCs, copackaged products, and adjunctive 
therapies. An FDC is a product in which two or more separate drug 
components (active pharmaceutical ingredients) are combined in a single 
dosage form. A copackaged product consists of two or more separate drug 
products in their final dosage form, packaged together with appropriate 
labeling to support the combination use. An adjunctive therapy refers 
to the situation in which a patient is maintained on a second drug 
product that is used together with (i.e., in adjunct to) the primary 
treatment, although the relative doses are not fixed and the drugs need 
not be given at the same time. Adjunctive therapy products may or may 
not be labeled for concomitant use. The guidance discusses all three 
types of drug combinations. However, it is only intended to describe 
general guiding principles. To receive more detailed

[[Page 3715]]

advice regarding a particular drug combination development program, a 
sponsor should contact the appropriate review division before 
submitting an Investigational New Drug application. In addition, FDA is 
in the process of publishing more specific guidance for certain 
categories of drug combinations.
    The guidance discusses drug combinations involving the following 
items: (1) Previously marketed drugs, (2) one or more new molecular 
entities (NMEs) and one or more previously marketed drugs, and (3) more 
than one NME. The nonclinical studies considered important for each 
type of combination may differ, depending upon the information 
available on each drug component (active pharmaceutical ingredient). 
The nonclinical studies that would be appropriate to adequately 
characterize the combination depend on the toxicologic and 
pharmacokinetic profiles of the individual drugs, the treatment 
indication or indications, and the intended population.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on nonclinical 
safety evaluation of drug combinations. 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 requirements of the applicable statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the draft guidance. 
Two copies of mailed comments are to be submitted, except that 
individuals may submit one copy. Comments are to be identified with the 
docket number found in brackets in the heading of this document. The 
draft guidance and received comments are available for public 
examination in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/ohrms/dockets/default.htm.

    Dated: January 18, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-1394 Filed 1-25-05; 8:45 am]
BILLING CODE 4160-01-S