59258 Federal Register / Vol. 69, No. 191 / Monday, October 4, 2004 / Notices 

1FDA 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.

approach may be used if the approach 

satisfies the requirements of the 

applicable statutes and regulations.

III. Electronic Access

Persons with access to the Internet 

may obtain the guidance at either http:/

/www.fda.gov/cder/guidance/index.htm

or http://www.fda.gov/ohrms/dockets/

default.htm.

Dated: September 28, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–22203 Filed 9–29–04; 1:51 pm]

BILLING CODE 4160–01–S

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://

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 

(www.pqri.org).1 The draft guidance was 

published on September 3, 2003.

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 

Federal Register / Vol. 69, No. 191 / Monday, October 4, 2004 / Notices 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:/

/www.fda.gov/cder/guidance/index.htm

or 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

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D–0414]

Guidance for Industry on Food and 

Drug Administration Review of Vaccine 

Labeling Requirements for Warnings, 

Use Instructions, and Precautionary 

Information; Availability

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a document entitled 

‘‘Guidance for Industry: FDA Review of 

Vaccine Labeling Requirements for 

Warnings, Use Instructions, and 

Precautionary Information,’’ dated 

September 2004. The guidance 

document provides to vaccine 

manufacturers, medical practitioners, 

and consumers an overview of the 

vaccine labeling review process, a 

description of FDA’s review of 

childhood vaccine labeling, and a 

discussion of the type of data FDA 

examines when determining the 

adequacy of vaccine labeling.

DATES: Submit written or electronic 

comments on agency guidances at any 

time.

ADDRESSES: Submit written requests for 

single copies of the guidance to 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. Send one 

self-addressed adhesive label to assist 

the office in processing your requests. 

The guidance may also be obtained by 

mail by calling the CBER Voice 

Information System at 1–800–835–4709 

or 301–827–1800. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the guidance 

document.

Submit written comments on the 

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://

www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT:

Astrid Szeto, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, suite 

200N, 1401 Rockville Pike, Rockville, 

MD 20852–1448, 301–827–6210.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of 

a document entitled ‘‘Guidance for 

Industry: FDA Review of Vaccine 

Labeling Requirements for Warnings, 

Use Instructions, and Precautionary 

Information,’’ dated September 2004. 

The guidance document provides to 

vaccine manufacturers, medical 

practitioners, and consumers an 

overview of the vaccine labeling review 

process, a description of FDA’s review 

of childhood vaccine labeling under 

section 314 of the National Childhood 

Vaccine Injury Act (NCVIA), and a 

discussion of the type of data FDA 

examines when determining the 

adequacy of vaccine labeling. The 

processes described represent current 

FDA practices and do not represent any 

new interpretation of existing labeling 

statutes, regulations, or guidances.

The guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the agency’s 

current thinking on this topic. 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 statutes and regulations.

II. Comments

In accordance with 21 CFR 

10.115(g)(4)(i), FDA is immediately 

implementing this guidance. Interested 

persons may, at any time, submit 

written or electronic comments to the 

Division of Dockets Management (see 

ADDRESSES) regarding this guidance. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in the brackets in 

the heading of this document. A copy of 

the guidance and received comments 

are available for public examination in 

the Division of Dockets Management 

between 9 a.m. and 4 p.m., Monday 

through Friday.

III. Electronic Access

Persons with access to the Internet 

may obtain the guidance at either http:/

/www.fda.gov/cber/guidelines.htm or 

http://www.fda.gov/ohrms/dockets/

default.htm.

Dated: September 20, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–22213 Filed 10–1–04; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Children’s Hospitals Graduate Medical 

Education Payment Program (CHGME 

PP)

AGENCY: Health Resources and Services 

Administration, HHS.

ACTION: Notice of Children’s Hospitals 

Graduate Medical Education Payment 

Program (CHGME PP) conference call. 

SUMMARY: This document announces a 

scheduled CHGME PP conference call 

for Federal fiscal year (FY) 2005. The