[Federal Register: November 14, 2003 (Volume 68, Number 220)]
[Notices]
[Page 64628-64629]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr14no03-82]
-----------------------------------------------------------------------
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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.
v/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