[Federal Register: October 4, 2004 (Volume 69, Number 191)]
[Notices]               
[Page 59258-59259]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04oc04-80]                         

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Docket No. 2003D-0382]

Food and Drug Administration

 
Guidance for Industry on Sterile Drug Products Produced by 
Aseptic Processing--Current Good Manufacturing Practice

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Sterile Drug 
Products Produced by Aseptic Processing--Current Good Manufacturing 
Practice.'' This guidance explains FDA's current thinking on 
manufacturing of sterile drug products produced by aseptic processing 
in the context of complying with certain sections of the current good 
manufacturing practice (CGMP) regulations for drug and biological 
products. This guidance is issued with the goal of providing clear and 
consistent communication of regulatory expectations to promote 
voluntary compliance with current FDA requirements.

DATES: General comments on agency guidance documents are welcome at any 
time.

ADDRESSES: 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, Food and Drug Administration, 1401 Rockville Pike, Rockville, 
MD 20852-1448. Send one self-addressed adhesive label to assist that 
office in processing your requests. Submit written comments on the 
draft guidance to the Division of Dockets Management (HFA-305), Food 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.
 See the SUPPLEMENTARY INFORMATION section for electronic 

access to the guidance document.

FOR FURTHER INFORMATION CONTACT:
    Richard Friedman, Center for Drug Evaluation and Research (HFD-
320), Food and Drug Administration, 11919 Rockville Pike, Rockville, MD 
20852, 301-827-9031; or
    Robert Sausville, Center for Biologics Evaluations and Research 
(HFM-624), Food and Drug Administration, 1401 Rockville Pike, 
Rockville, MD 20852-1448, 301-827-6201; or
    Robert Coleman, Office of Regulatory Affairs (HFC-240), Food and 
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 404-253-
1295.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Sterile Drug Products Produced by Aseptic Processing-- 
Current Good Manufacturing Practice.'' This guidance explains FDA's 
current thinking on manufacturing of sterile drug products produced by 
aseptic processing in the context of complying with certain sections of 
the CGMP regulations for drug and biological products (21 CFR parts 
210, 211, and 600 through 680, respectively).
    In the Federal Register of September 5, 2003 (68 FR 52782), FDA 
announced the availability of a draft guidance entitled ``Sterile Drug 
Products Produced by Aseptic Processing-- Current Good Manufacturing 
Practice.'' The draft guidance was finalized after consideration of 
received public comments. Consistent with the objectives of FDA's CGMPs 
for the 21st Century initiative, this guidance provides updated 
information regarding CGMP expectations for aseptic processing 
facilities, reflects the latest science in the area of sterile drug 
quality, and promotes innovations in manufacturing that achieve 
increased sterility assurance. Through this guidance, FDA hopes to 
facilitate a higher assurance of process consistency and promote better 
contamination prevention practices.
    Sterile drug products are a high priority in FDA's risk-based 
inspectional program. These drug products are generally of high 
therapeutic significance. Clarifying relevant regulatory standards for 
sterile drug products will help reduce the incidence of manufacturing 
problems with this class of pharmaceuticals, thus facilitating the 
ready availability of these therapeutically significant pharmaceuticals 
and avoiding drug shortages.
    This guidance document is the product of extensive public input. 
FDA first published a preview of its current thinking in the form of a 
concept paper on September 23, 2003. We presented our CGMP approach for 
aseptic processing at the Advisory Committee for Pharmaceutical Science 
on October 22, 2002. At this meeting, the concept paper was discussed 
in a public forum and critiqued by the advisory committee's members as 
well as a panel of invited aseptic processing experts. The advisory 
committee meeting yielded a number of issues that provided impetus for 
further discussion. In December 2002, an aseptic processing working 
group was formed under Product Quality Research Institute (PQRI) to 
address these issues. The working group, composed of 41 prominent 
aseptic processing experts from industry, academia, and FDA, prepared 
technical recommendations on the guidance document. The PQRI Steering 
Committee forwarded the working group's final report to FDA on March 
19, 2003, and it was subsequently posted on PQRI's Web site 
(http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.pqri.org).\1\ The draft guidance was published on September 3, 

2003.
---------------------------------------------------------------------------

    \1\ FDA has verified the Web site address, but FDA is not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.
---------------------------------------------------------------------------

    The advisory committee and PQRI Working Group recommendations 
provided valuable contributions and many of these recommendations have 
been adopted in the guidance.

II. Comments Received on the Draft Guidance

    A number of comments were received on the draft guidance, most of 
which concerned the need to further enhance the precision of guidance 
provided on certain topics. As a result, many clarifying changes were 
made. Major changes include the revision of the Sterility Testing 
section of the guidance to clearly emphasize and reference the United 
States Pharmacopeial Sterility Test <71>. In the guidance, table 1 
entitled ``Air Classifications,'' which

[[Page 59259]]

summarizes clean area air classifications and recommended 
microbiological action levels, has been modified to acknowledge that 
alternate action levels can be justified depending on the method of 
analysis used. Further clarifications have been made regarding process 
simulations. In addition, the guidance recommends ``building quality 
into products'' through science-based facility, equipment, and systems 
design for sterile drug manufacture. We underscore our encouragement of 
alternate approaches and innovations to achieve increased sterility 
assurance.
    This level 1 guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The guidance represents 
the agency's current thinking. 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 the approach satisfies the 
requirements of the applicable statute and regulations.

III. Paperwork Reduction Act of 1995

    This guidance contains information collection provisions that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520). The 
collection of information in this guidance was approved under OMB 
control number 0910-0139, until August 31, 2005.

IV. Electronic Access

    Persons with access to the Internet may obtain the guidance at 
either 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm.
    Dated: September 28, 2004.

Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-22207 Filed 9-29-04; 2:14 pm]

BILLING CODE 4160-01-S