[Federal Register Volume 68, Number 220 (Friday, November 14, 2003)]
[Notices]
[Pages 64628-64629]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-28457]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 1996D-0009]


International Conference on Harmonisation; Revised Guidance on 
Q3B(R) Impurities in New Drug Products; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a revised guidance entitled ``Q3B(R) Impurities in New 
Drug Products.'' The revised guidance, which updates a guidance on the 
same topic published in the Federal Register of May 19, 1997 (the 1997 
guidance), was prepared under the auspices of the International 
Conference on Harmonisation of Technical Requirements for Registration 
of Pharmaceuticals for Human Use (ICH). The revised guidance is 
intended to provide guidance to applicants for drug marketing 
registration on the content and qualification of impurities in new drug 
products produced by chemically synthesized new drug substances not 
previously registered in a country, region, or member State. The 
revised guidance clarifies the 1997 guidance, adds information, and 
provides consistency with more recently published ICH guidances. The 
revised guidance complements the ICH guidance entitled ``Q3A(R) 
Impurities in New Drug Substances.''

DATES: The guidance is effective November 14, 2003. Submit written or 
electronic comments at any time.

ADDRESSES: Submit written comments on the 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. Submit written requests for 
single copies of the 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, or the Office 
of Communication, Training and Manufacturers Assistance (HFM-40), 
Center for Biologics Evaluation and Research (CBER), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
3844, FAX: 888-CBERFAX. Send two self-addressed adhesive labels to 
assist the office in processing your request. Requests and comments 
should be identified with the docket number found in brackets in the 
heading of this document. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Charles P. Hoiberg, Center for Drug 
Evaluation and Research (HFD-800), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-5918; or
    Andrew Shrake, Center for Biologics Evaluation and Research (HFM-
345), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 
20052-1148, 301-402-4635.
    Regarding the ICH: Michelle Limoli, Office of International 
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-0864.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
harmonization initiatives to be developed with input from both 
regulatory and industry representatives. FDA also seeks input from 
consumer representatives and others. ICH is concerned with 
harmonization of technical requirements for the registration of 
pharmaceutical products among three regions: The European Union, Japan, 
and the United States. The six ICH sponsors are the European 
Commission, the European Federation of Pharmaceutical Industries 
Associations, the Japanese Ministry of Health, Labour, and Welfare, and 
the Japanese Pharmaceutical Manufacturers Association, the Centers for 
Drug Evaluation and Research and Biologics Evaluation and Research, 
FDA, and the Pharmaceutical Research and Manufacturers of America. The 
ICH Secretariat, which coordinates the preparation of documentation, is 
provided by the International Federation of Pharmaceutical 
Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization, the Health Canada's Health Products and Food 
Branch, and the European Free Trade Area.
    In the Federal Register of February 11, 2003 (68 FR 6924), the 
agency published an ICH guidance entitled ``Q3A(R) Impurities in New 
Drug Substances,'' which revised Q3A. The guidance Q3A(R) provides 
recommendations to applicants for drug marketing registration on the 
content and qualification of impurities in new drug substances produced 
by chemical synthesis and not previously registered in a country, 
region, or member state.
    In the Federal Register of July 19, 2000 (65 FR 44791), FDA 
published a draft tripartite guidance entitled ``Q3B(R) Impurities in 
New Drug Products.'' The notice gave interested persons an opportunity 
to submit comments by September 18, 2000.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee; the three participating regulatory agencies 
endorsed it in February 2003.
    This revised guidance complements the ICH Q3A(R) guidance and 
provides recommendations for registration or marketing applications on 
the content and qualification of impurities in new drug products 
produced from chemically synthesized new drug substances not previously 
registered in a region or member state. The revised guidance addresses 
only those impurities in new drug products

[[Page 64629]]

classified as degradation products of the drug substance or reaction 
products of the drug substance with an excipient and/or immediate 
container closure system. Impurities arising from excipients present in 
the new drug product or extracted or leached from the container closure 
system are not addressed in this revised guidance.
    The Q3B(R) guidance has been revised to add information to certain 
sections and to provide clarification to other sections of the previous 
guidance. The most important sections that have been revised are:
    [sbull] The text on reporting, identification, and qualification 
thresholds.
    [sbull] The text on the listing of impurities in specifications and 
a clear distinction between ICH Q3B (listing impurities) and Q6A 
(setting specifications).
    [sbull] The deletion of the exception to conventional rounding 
practice, i.e., the provision recommending no rounding up to 0.1 
percent for values between 0.05 and 0.09 percent.
    [sbull] Attachment 2--an illustration of reporting degradation 
product results for identification and qualification in an application.
    [sbull] Attachment 3--a decision tree for identification and 
qualification of a degradation product.
    [sbull] Additions and revisions to the previous glossary including 
definitions for the terms ``unspecified degradation product,'' 
``reporting threshold,'' ``identification threshold,'' and 
``qualification threshold.''
    [sbull] References to more recently published ICH guidances (e.g., 
``Q3A(R) Impurities in New Drug Substances,'' Q3C Impurities: Residual 
Solvents,'' and ``Q6A Specifications: Test Procedures and Acceptance 
Criteria for New Drug Substances and New Drug Products: Chemical 
Substances'').
    In addition, minor editorial changes were made to improve the 
clarity and consistency of the document.
    This guidance represents the agency's current thinking on this 
topic. 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 guidance at any 
time. Two copies of any mailed comments are to be submitted, except 
individuals may submit one copy. Comments are to be identified with the 
docket number found in brackets in the heading of this document. The 
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 
http://www.fda.gov/ohrms/dockets/default.htm, http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.

    Dated: November 4, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy
[FR Doc. 03-28457 Filed 11-13-03; 8:45 am]
BILLING CODE 4160-01-S