[Federal Register: November 21, 2003 (Volume 68, Number 225)]
[Notices]
[Page 65717-65718]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr21no03-79]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2002D-0231 and 1993D-0139]
International Conference on Harmonisation; Stability Data Package
for Registration Applications in Climatic Zones III and IV; Stability
Testing of New Drug Substances and Products; 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 two guidances prepared under the auspices of the
International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH). The first is a
guidance entitled ``Q1F Stability Data Package for Registration
Applications in Climatic Zones III and IV'' (the Q1F guidance). The
second is a revised guidance entitled ``Q1A(R2) Stability Testing of
New Drug Substances and Products'' (the Q1A guidance). The Q1F
guidance, which is an annex to the Q1A guidance, defines an approach
for broader use of the Q1A guidance for territories in climatic zones
III and IV. The revised Q1A guidance incorporates relevant Q1F
recommendations.
DATES: The guidance is effective November 21, 2003. Submit written
comments at any time.
ADDRESSES: Submit written comments on the guidances 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 guidances 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 requests. 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 guidance documents.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidances: Chi-wan Chen, Center for Drug Evaluation
and Research (HFD-830), Food and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857, 301-827-2001; 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 harmonisation of regulatory requirements. FDA has
participated in many meetings designed to enhance harmonisation 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.
[[Page 65718]]
ICH was organized to provide an opportunity for tripartite
harmonisation 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
harmonisation 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; 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 (WHO), Health Canada's Health Products and Food
Branch, and the European Free Trade Area.
In the Federal Register of June 14, 2002 (67 FR 40951), FDA
published a notice announcing the availability of a draft tripartite
guidance entitled ``Q1F Stability Data Package for Registration in
Climatic Zones III and IV.'' In the same notice, the agency announced
that when the Q1F guidance was finalized, the Q1A guidance, originally
published in the Federal Register of September 22, 1994 (59 FR 48754),
and revised (as Q1A(R)) in 2001 (66 FR 56332, November 7, 2001), would
be revised to incorporate the relevant information from the Q1F
guidance. The notice gave interested persons an opportunity to submit
comments by August 20, 2002.
After consideration of the comments received and revisions to the
guidance, a final draft of the Q1F guidance was submitted to the ICH
Steering Committee and endorsed by the three participating regulatory
agencies on February 6, 2003. On the same date, the ICH Steering
Committee endorsed the revised Q1A guidance incorporating the Q1F
recommendations.
II. The Guidances
There are four climatic zones in the world that are distinguished
by their characteristic prevalent annual climatic conditions, based on
the concept described by P. Schumacher (Pharmazeutische Zeitung,
119:321-324, 1974). The Q1A guidance defines the stability data package
for the ICH tripartite regions (the EU, Japan, and the United States),
which are in climatic zones I or II. The WHO has published a guideline
on ``Stability testing of pharmaceutical products containing well
established drug substances in conventional dosage forms'' (WHO
technical report series, no. 863, annex 5), updated in the ``Report of
the thirty-seventh meeting of the WHO Expert Committee on
Specifications for Pharmaceutical Preparations,'' Geneva, October 22-
26, 2001. The WHO guideline defines stability testing recommendations,
including storage conditions, for all four climatic zones.
A. The Q1F Guidance
The Q1F guidance establishes harmonized global stability testing
recommendations based on the Q1A guidance and the WHO guideline and
defines an approach for broader use of Q1A recommendations for
territories in climatic zones III and IV. For territories in climatic
zones III and IV, the data package as described in the Q1A guidance can
be considered applicable except for certain storage conditions. The Q1F
guidance recommends the ``room termperature'' long-term storage
conditions and other considerations as part of the data package
considered sufficient for a registration application for drug
substances and products intended to be marketed in climatic zones III
and IV.
B. The Revised Q1A Guidance
In concert with the Q1F recommendations, the intermediate storage
condition for the ``general case'' in the Q1A guidance has been changed
from 30 [deg]C +/- 2 [deg]C/60 percent relative humidity (RH) +/- 5
percent RH. The new intermediate storage condition for the general case
is now 30 [deg]C +/- 2 [deg]C/65 percent RH +/- 5 percent RH. This
change, from 60 percent RH to 65 percent RH, is intended to harmonize
the intermediate storage condition for zones I and II with the long-
term condition for zones III and IV. Furthermore, this modified
intermediate condition can be used as an alternative long-term
condition to 25 [deg]C +/- 2 [deg]C/60 percent RH +/- 5 percent RH for
zones I and II.
These guidance documents represent the agency's current thinking on
this topic. They do not create or confer any rights for or on any
person and do 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.
III. Comments
Interested persons may, at any time, submit to the Division of
Dockets Management (see ADDRESSES) written comments on the guidances.
Two copies of any 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 guidances
and received comments may be seen in the office above between 9 a.m.
and 4 p.m., Monday through Friday.
IV. Electronic Access
Persons with access to the Internet may obtain the documents 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 14, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-29103 Filed 11-20-03; 8:45 am]
BILLING CODE 4160-01-S