International Conference on Harmonisation; Guidance on Good Manufacturing Practice for Active Pharmaceutical Ingredients; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled “Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients.” The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes current good manufacturing practice (CGMP) for manufacturing of active pharmaceutical ingredients (APIs). The guidance is intended to help ensure that all APIs meet the standards for quality and purity they purport or are represented to possess.

DATES:

The guidance is effective September 25, 2001. Submit written or electronic comments on agency guidances at any time.

ADDRESSES:

Submit written requests for single copies of the guidance to the Drug Information Branch (HFD-210), 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), 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. Submit written comments on the guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. 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 document.

FOR FURTHER INFORMATION CONTACT:

Regarding the guidance: Edwin Rivera, Center for Drug Evaluation and Research (HFD-320), Food and Drug Administration, 7520 Standish Pl., Rockville, MD 20855, 301-594-0095, Rivera@cder.fda.gov, or John A. Eltermann, Center for Biologics Evaluation and Research (HFM-670), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-3031, Eltermann@cber.fda.gov.

Regarding the ICH: Janet J. Showalter, Office of Health Affairs (HFY-20), 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 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, the Canadian Health Protection Branch, and the European Free Trade Area.

In accordance with the agency’s good guidance practices (GGPs) regulation (21 CFR 10.115), this document is being called a guidance, rather than a guideline.

To facilitate the process of making ICH guidances available to the public, the agency has changed its procedures for publishing ICH guidances. As of April 2000, FDA no longer includes the text of ICH guidances in the Federal Register. Instead, the agency publishes a notice in the Federal Register announcing the availability of an ICH guidance. The ICH guidance is placed in the docket and can be obtained through regular agency sources (see the ADDRESSES section). Draft ICH guidances are left in the original ICH format. Final guidances are reformatted to conform to the GGP style before publication.

In the Federal Register of August 1, 2000 (65 FR 46936), FDA published a notice announcing the availability of the draft guidance entitled “Q7A ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients.” The notice gave interested persons an opportunity to submit comments by October 2, 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 and endorsed by the three participating regulatory agencies in November 2000.

The guidance describes CGMPs for the manufacturing of APIs. The guidance is intended to help ensure that all APIs meet the standards for quality and purity they purport or are represented to possess. The guidance is not intended to define registration or filing requirements or modify pharmacopeial requirements.

In the guidance, “manufacturing” includes all operations, and related controls, of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage, and distribution of APIs. The guidance applies to the manufacture of APIs for use in human drug products, including sterile APIs up to the point immediately before the API is rendered sterile. The sterilization and aseptic processing of sterile APIs are not covered by this guidance. CGMP's described in the guidance should be applied to the API manufacturing process beginning with the use of API starting materials.

The guidance applies to APIs that are manufactured by chemical synthesis, extraction, cell culture/fermentation, recovery from natural sources, or any combination of these processes. APIs manufactured using blood or plasma as raw materials are also covered.

The guidance does not apply to vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation), and gene therapy APIs. The guidance does not apply to cell substrates, medical gases, bulk-packaged drug products, and manufacturing/control aspects specific to radiopharmaceuticals.

This guidance represents the agency's current thinking on CGMPs for manufacturing APIs. 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 Dockets Management Branch (address above) written or electronic comments on the guidance at any time. 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 draft guidance and received comments are available for public examination in the Dockets Management Branch 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 http://www.fda.gov/cber/publications.htm.