Draft Guidance for Industry on Nonclinical Safety Evaluation of Drug Combinations; Availability, 3714-3715 [05-1394]

Download as PDF 3714 Federal Register / Vol. 70, No. 16 / Wednesday, January 26, 2005 / Notices ESTIMATED ANNUAL REPORTING BURDEN1—Continued No. of Respondents ≤Requests for Tier-Two Dispute Resolution No. of Responses per Respondent 5 Total Annual Responses 1 Hours per Response 5 8 Total 1 There Total Hours 40 790 are no capital costs or operating and maintenance costs associated with this collection. In the Federal Register of September 5, 2003 (68 FR 52777), FDA announced the availability of a draft guidance for industry entitled ‘‘Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP.’’ The notice requested comments on the information collection estimates within 60 days. No comments were received on the information collection estimates. This document requests comments on the information collection burden that FDA estimates will result from the draft guidance. The draft guidance was drafted as part of FDA’s initiative ‘‘Pharmaceutical cGMPs for the 21st Century: A RiskBased Approach,’’ which was announced in August 2002. The initiative focuses on FDA’s current CGMP program and covers the manufacture of veterinary and human drugs, including human biological drug products. The agency formed the DR Working Group comprising representatives from ORA, the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, and the Center for Veterinary Medicine. The working group met weekly on issues related to the DR process and met with stakeholders in December 2002 to seek their input. The draft guidance was initiated in response to industry’s request for a formal DR process to resolve differences related to scientific and technical issues that arise between investigators and pharmaceutical manufacturers during FDA inspections of foreign and domestic manufacturers. In addition to encouraging manufacturers to use currently available DR processes, the draft guidance describes a formal twotiered DR process that provides a formal mechanism for requesting review and decision on issues that arise during inspections: • Tier-one of the DR process provides a mechanism to raise scientific or technical issues to the ORA and center levels. • Tier-two of the DR process provides a mechanism to raise scientific or technical issues to the agency’s DR Panel for Scientific and Technical Issues VerDate jul<14>2003 19:33 Jan 25, 2005 Jkt 205001 Related to Pharmaceutical CGMP (DR Panel). The draft guidance also covers the following topics: • The suitability of certain issues for the formal DR process, including examples of some issues with a discussion of their appropriateness for the DR process. • Instructions on how to submit requests for formal DR and a list of the supporting information that should accompany these requests. • Public availability of decisions reached during the DR process to promote consistent application and interpretation of drug quality-related regulations. Dated: January 18, 2005. Jeffrey Shuren, Assistant Commissioner for Policy. [FR Doc. 05–1396 Filed 1–25–05; 8:45 am] BILLING CODE 4160–01–S 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. 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 fixeddose combination products (FDCs), copackaged products, and adjunctive therapies. Submit written or electronic comments on the draft guidance by April 26, 2005. General comments on agency guidance documents are welcome at any time. DATES: PO 00000 Frm 00045 Fmt 4703 Sfmt 4703 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 selfaddressed 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 https:// 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: ADDRESSES: 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 E:\FR\FM\26JAN1.SGM 26JAN1 Federal Register / Vol. 70, No. 16 / Wednesday, January 26, 2005 / Notices 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 https://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 VerDate jul<14>2003 19:33 Jan 25, 2005 Jkt 205001 3715 for diagnostic and therapeutic purposes. The role of the CRADA collaborator(s) will include, but not be limited to, the National Institutes of Health following: 1. The ability to collaborate with National Heart, Lung, and Blood NHLBI on further research and Institute (NHLBI); Opportunity for a development of this technology. This Cooperative Research and ability can be demonstrated through Development Agreement (CRADA) to experience and expertise in this or Identify and Explore Epigenetic related areas of technology indicating Regulatory Elements for Diagnostic the ability to contribute intellectually to and Therapeutics Purposes on-going research and development. 2. To assist with obtaining specimen/ AGENCY: National Institutes of Health, tissues (patient and normal controls) for Public Health Service, HHS. the Genome-Wide analysis as diagnostic ACTION: Notice. and therapeutic markers. 3. To assist to further developing the SUMMARY: The National Heart, Lung, and epigenetic regulatory elements markers/ Blood Institute (NHLBI) is seeking acetylation islands as new targets for Cooperative Research and Development novel drug-development strategies. Agreement (CRADA) collaborator(s) to The collaborator may also be expected work with investigators in the to contribute financial support under Laboratory of Molecular Immunology this CRADA for personnel, supplies, (LMI) to identify epigenetic regulatory travel, and equipment to support these elements that may be involved in the projects. The collaborator is also disease development of T and/or B cell expected to cooperate with the NHLBI leukemia/lymphoma and other cancers in the timely publication of research via genome-wide analysis of acetylation results and to accept the legal islands using the Genome-Wide provisions and language of the CRADA Mapping Technique (GMAT). with only minor modifcations, if any. Representative disease-specific DATES: CRADA capability statements acetylation islands will be explored for should be submitted to Vincent diagnostic and therapeutic purposes. Kolesnitchenko, Ph.D., Technology SUPPLEMENTARY INFORMATION: Transfer Specialist, National Heart, Epigenetics play a critical role in Lung, and Blood Institute (NHLBI), cellular development and cellular Office of Technology Transfer and transformation in many pathogenic Development, National Institutes of processes. For example, many cancers Health, 6705 Rockledge Drive, Suite are correlated with changes of their 6018, MSC 7992, Bethesda, MD 20892– chromatin structure and are sensitive to 7992; Phone: (301) 594–4115; Fax: (301) drugs that modulate the levels of 594–3080; E-mail: vk5q@nih.gov. histone acetylation. Epigenetic Capability statements must be received regulation refers to the modification of on or before March 28, 2005. chromatin including posttranslational The NHLBI has applied for patents modification of histones, which does claiming the core of the technology. not involve change of DNA sequences of Non-exclusive and/or exclusive licenses target genes. MHLBI investigators have for these patents covering core aspects mapped the genome-wide distribution of this project are available to interested of histone H3 acetylation in human T parties. cells and discovered over 40,000 Licensing inquiries regarding this acetylation islands using a technique technology should be addressed to John called GMAT. This tool combines Stansberry, Ph.D., Technology Licensing Chromatin immunoprecipitation (Chip) Specialist, Office of Technology of hyper-acetylated histones, with Serial Transfer, National Institutes of Health, Analysis of Gene Expression (SAGE). 6011 Executive Boulevard, Suite 325, The acetylation islands are epigenetic Rockville, Maryland 20852–3804, markers for transcriptional regulatory Phone: (301) 435–5236; Fax: (301) 402– elements and chromatin controlling 0220; E-mail: stansbej@od.nih.gov. elements. Changes of the acetylation Information about Patent Applications islands may be correlated with early and pertinent information not yet development of T cell lymphoma or publicly described an be obtained under leukemia. Therefore, this discovery may the terms of a Confidential Disclosure be applied to early diagnosis and/or Agreement. Respondents interested in submitting treatment of these diseases. The NHLBI is seeking capability a CRADA Proposal should be aware that statements from parties interested in it may be necessary to secure a license entering into a CRADA to identify, to the above-mentioned patent rights in explore and further develop epigenetic order to commercialize products arising regulatory elements/acetylation islands from a CRADA. DEPARTMENT OF HEALTH AND HUMAN SERVICES PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 E:\FR\FM\26JAN1.SGM 26JAN1

Agencies

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


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 https://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 https://www.fda.gov/cder/guidance/index.htm or https://
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

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