[Federal Register Volume 68, Number 225 (Friday, November 21, 2003)]
[Notices]
[Pages 65717-65718]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-29103]


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

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.

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

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://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://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 14, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-29103 Filed 11-20-03; 8:45 am]
BILLING CODE 4160-01-S