[Federal Register Volume 63, Number 74 (Friday, April 17, 1998)]
[Notices]
[Pages 19267-19268]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-10312]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98D-0193]


Draft Guidance for Industry on Manufacturing, Processing, or 
Holding 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availability of a draft guidance for industry entitled ``Manufacturing, 
Processing, or Holding Active Pharmaceutical Ingredients.'' This draft 
guidance is intended to provide guidance on current good manufacturing 
practices (CGMP's) for manufacturing, processing, packing, or holding 
active pharmaceutical ingredients (API's). The draft guidance is 
intended to help ensure the quality and suitability of API's for use in 
the manufacture of drug products.

DATES: Written comments may be submitted on the draft guidance by May 
18, 1998. General comments on agency guidances are welcome at any time.

ADDRESSES: Copies of this draft guidance are available on the Internet 
at http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/
cber/guidelines.htm.
    Submit written comments on the draft guidance to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 12420 
Parklawn Dr., rm. 1-23, Rockville, MD 20857. 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.

FOR FURTHER INFORMATION CONTACT: Edwin M. Rivera, Center for Drug 
Evaluation and Research (HFD-322), 7520 Standish Pl., Rockville, MD 
20855, 301-594-0095; John A. Eltermann, Center for Biologics Evaluation 
and Research (HFM-205), 1401 Rockville Pike, Rockville, MD 20852, 301-
827-3031; or Jose R. Laureano, Center for Veterinary Medicine (HFV-
230), 7500 Standish Pl., Rockville, MD 20855, 301-594-1785.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a 
draft guidance for industry entitled ``Manufacturing, Processing, or 
Holding Active Pharmaceutical Ingredients.'' It provides guidance on 
CGMP's for the manufacture, processing, packing, or holding (i.e., 
storage) of API's.
    The draft guidance is a result of extensive efforts that began in 
July 1995 when FDA decided to develop an industry guidance for the 
manufacture and control of API's. An initial draft of this guidance for 
industry was widely distributed during 1996. It was reviewed at a 
September 1996 international conference on API's in Canberra, 
Australia, sponsored by the Pharmaceutical Inspection Convention/
Pharmaceutical Inspection Convention Scheme (PIC-PIC/S), and at the 
October 1996 annual FDA/Parenteral Drug Association Forum in Bethesda, 
MD. It also was distributed to numerous pharmaceutical trade 
associations in a letter from the Center for Drug Evaluation and 
Research's (CDER) Office of Compliance, dated November 8, 1996. The 
initial draft was posted on CDER's website on November 12, 1996, with a 
request for comments by December 10, 1996. On December 9, the deadline 
for comments was extended until January 31, 1997. This draft guidance 
incorporates recommendations received at the two conferences and 
comments from 27 organizations, including API manufacturers, dosage 
manufacturers, and pharmaceutical associations.
    At a February 4 and 5, 1998, meeting of the International 
Conference on Harmonisation (ICH) Steering Committee in Tyson's Corner, 
VA, FDA supported the decision to develop internationally harmonized 
guidance on CGMP's for API's through the ICH process. The agency agreed 
to participate in an expert working group that will review numerous 
guidance documents developed by industry and regulatory bodies to 
develop a single harmonized ICH guidance. API/CGMP guidances to be 
reviewed by the working group include those prepared by the European 
Chemical Industry Council/European Federation of Pharmaceutical 
Industries' Association, the Pharmaceutical Research and Manufacturers 
of America, PIC-PIC/S, and the World Health Organization. This draft 
guidance will also be considered by the working group.
    The draft guidance applies to the manufacture and control of drug 
and biologic API's for use in human and veterinary drug products. In 
addition, it applies to the later chemical isolation and purification 
steps of API's derived from biological or fermentation processes and to 
sterile API's, but only up to the point where the API is

[[Page 19268]]

rendered sterile. The document also identifies CGMP's for the 
manufacture of API's used in the production of drug products for 
clinical trials.
    The draft guidance incorporates the following two fundamental 
concepts in API production: (1) Application of CGMP controls to all 
steps in the manufacturing process, beginning with the use of starting 
materials; and (2) validation of those steps determined to be critical 
to the quality and purity of the final API. The guidance clarifies the 
agency's expectations regarding application of CGMP's (i.e., extent of 
written instructions, in-process controls, sampling, testing, 
monitoring, and documentation) to different steps of an API process.
    This draft guidance represents the agency's current thinking on the 
manufacture and control of API's. 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 requirement of the applicable statute, regulations, or both.
    Written requests for single copies of the guidance ``Manufacturing, 
Processing, or Holding Active Pharmaceutical Ingredients'' should be 
submitted to the Drug Information Branch (HFD-210), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to 
assist that office in processing your requests. Requests should be 
identified with the docket number found in brackets in the heading of 
this document. A copy 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.

    Dated: April 14, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-10312 Filed 4-15-98; 11:29 am]
BILLING CODE 4160-01-F