[Federal Register Volume 66, Number 33 (Friday, February 16, 2001)]
[Notices]
[Pages 10699-10700]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-3956]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D 0994]


Guidance for Industry on BACPAC I: Intermediates in Drug 
Substance Synthesis; Bulk Actives Postapproval Changes: Chemistry, 
Manufacturing, and Controls Documentation; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``BACPAC I: 
Intermediates in Drug Substance Synthesis; Bulk Actives Postapproval 
Changes: Chemistry, Manufacturing, and Controls Documentation.'' This 
guidance provides recommendations to holders of new drug applications, 
abbreviated new drug applications, new animal drug applications, 
abbreviated new animal drug applications, and drug master files or 
veterinary master files who intend, during the postapproval period, to 
change the site of manufacture, the scale of manufacture, the 
equipment, the specification(s), and/or the manufacturing process of 
intermediates in the synthetic pathway leading to the drug substance.

DATES: Submit written comments on agency guidances at any time.

ADDRESSES: Submit written requests for single copies of this guidance 
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. 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. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.

FOR FURTHER INFORMATION CONTACT: Kasturi Srinivasachar, Center for Drug 
Evaluation and Research (HFD-110), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-5376; or Dennis M. Bensley, 
Center for Veterinary Medicine (HFV-143), Food and Drug Administration, 
7500 Standish Pl., Rockville, MD 20855, 301-827-6956.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``BACPAC I: Intermediates in Drug Substance Synthesis; Bulk 
Actives Postapproval Changes: Chemistry, Manufacturing, and Controls 
Documentation.'' This guidance describes chemistry, manufacturing, and 
controls information and documentation in support of each change and 
provides recommendations on reporting categories. The guidance applies 
to synthetic drug substances and the synthetic steps involved in the 
preparation of semisynthetic drug substances. It is limited to 
structurally well-characterized drug substances where impurities can be 
monitored at the levels recommended. The guidance covers changes as 
follows: (1) Site, scale, and equipment changes involving the synthetic 
steps up to, and including, the step that produces the final 
intermediate; (2) specification changes for raw materials, starting 
materials, and intermediates, excluding the final intermediate; and (3) 
manufacturing process changes involving the synthetic steps up to and 
including the final intermediate. The guidance does not cover 
postapproval changes affecting: (1) Synthetic peptides, (2) 
oligonucleotides, (3) radiopharmaceuticals, (4) drug substances derived 
exclusively by isolation from natural sources or produced by procedures 
involving biotechnology, or (5) nonsynthetic steps for semisynthetic 
drug substances. Also excluded from this guidance are certain changes 
in specification and process associated with the use of raw materials 
or starting materials derived from natural sources or biotechnology.
    In the Federal Register of November 30, 1998 (63 FR 65793), FDA 
announced the availability of a draft version of this guidance. The 
November 1998 guidance gave interested persons an opportunity to submit 
comments through March 31, 1999. All comments received during the 
comment period have been carefully reviewed and incorporated in this 
revised guidance where appropriate. As a result of the public comment, 
the guidance is clearer and more concise than the draft version.
    This Level 1 guidance is being issued consistent with FDA's good 
guidance

[[Page 10700]]

practices regulation (21 CFR 10.115; 65 FR 56468, September 19, 2000). 
The guidance represents the agency's current thinking on intermediates 
in drug substance synthesis, bulk actives postapproval changes, 
chemistry, manufacturing, and controls documentation. 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, at any time, submit written comments on the 
guidance to the Dockets Management Branch (address above). 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 guidance. The 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 
http://www.fda.gov/cder/guidance/index.htm or http://www.fda.gov/cvm.

    Dated: February 8, 2001.
Ann M. Witt,
Acting Associate Commissioner for Policy.
[FR Doc. 01-3956 Filed 2-15-01; 8:45 am]
BILLING CODE 4160-01-F