Guidance for Industry on Changes to an Approved NDA or ANDA; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 99D-0529]

Guidance for Industry on Changes to an Approved NDA or ANDA;

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 ``Changes to an

Approved NDA or ANDA.'' This guidance is intended to assist applicants

in determining how they should report changes to an approved new drug

application (NDA) or abbreviated new drug application (ANDA).

DATES: Written comments may be submitted at any time.

ADDRESSES: Copies of this guidance are available on the Internet at

http://www.fda.gov/cder/guidance/index.htm. Submit written requests for

single copies of this guidance for industry 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 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.

FOR FURTHER INFORMATION CONTACT: Nancy B. Sager, Center for Drug

Evaluation and Research (HFD-357), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-594-5633; e-mail:

[email protected], for questions about content of the guidance.

SUPPLEMENTARY INFORMATION: On November 21, 1997, the President signed

the Food and Drug Administration Modernization Act (the Modernization

Act) (Public Law 105-115). Section 116 of the Modernization Act amended

the Food, Drug, and Cosmetic Act (the act) by adding section 506A (21

U.S.C. 356a), which provides requirements for making and reporting

manufacturing changes to an approved application and for distributing a

drug product made with such changes.

FDA is announcing the availability of a guidance for industry

entitled ``Changes to an Approved NDA or ANDA Application.'' The

purpose of this guidance is to provide recommendations to holders of

NDA's and ANDA's who intend to make postapproval changes in accordance

with section 506A of the act. This guidance covers recommended

reporting categories for postapproval changes for drugs, other than

specified biotechnology and specified synthetic biological products.

Recommendations are provided for postapproval changes in: (1)

Components and composition, (2) manufacturing sites, (3) manufacturing

process, (4) specifications, (5) package, (6) labeling, (7)

miscellaneous changes, and (8) multiple related changes. This guidance

does not provide recommendations on the specific information that

should be developed by the applicant to assess the effect of the change

on the identity, strength (e.g., assay, content uniformity), quality

(e.g., physical, chemical, and biological properties), purity (e.g.,

impurities and degradation products), or potency (e.g., biological

activity, bioavailability, and bioequivalence) of a product as they may

relate to the safety or effectiveness of the product.

In the Federal Register of June 28, 1999 (64 FR 34660), FDA

announced the availability of a draft version of this guidance and gave

interested persons an opportunity to submit comments through August 27,

1999. All comments received during the comment period have been

carefully reviewed and incorporated in this revised guidance, where

appropriate.

The agency received multiple comments on three specific issues.

First, some comments objected to the agency's proposal to include as an

example of an annual report change ``Any change made to comply with an

official compendium that is consistent with FDA requirements and that

provides the same or greater level of assurance of the identity,

strength, quality, purity, or potency of the material being tested as

the analytical procedure described in the approved application.'' The

agency has revised this example as recommended in the comments to state

``Any change made to comply with an official compendium.'' Second, the

agency has removed from the guidance the recommendation ``list all

changes included in the supplement or annual report in the cover

letter.'' These issues, however, are still under consideration with

regard to FDA's proposal to amend its regulations entitled Supplements

and other changes to an approved application at Sec. 314.70 (21 CFR

314.70), which published in the Federal Register of June 28, 1999 (64

FR 34608). If necessary, FDA will revise this guidance to make it

consistent with the final rule for Sec. 314.70.

Third, the agency received comments requesting that the phrase

``change that may affect sterility assurance,'' which is used

throughout the guidance, be revised to, for example, ``change that may

significantly affect sterility assurance'' or ``change that may

adversely affect sterility assurance.'' FDA did not revise the guidance

as suggested because the phrase as proposed in the guidance is

consistent with the phrasing used in existing regulations (e.g., 21 CFR

601.12(b)(2)(vi)). If during the review of the comments on the proposed

rule to amend Sec. 314.70 FDA decides to revise this phrasing, this

guidance will be revised to make it consistent with the final rule for

Sec. 314.70.

This guidance is being issued consistent with FDA's good guidance

practices (62 FR 8961, February 27, 1997). It represents the agency's

current thinking on how it will apply the requirements of section 506A

of the act for NDA and ANDA products. 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 statute, regulations, or both.

FDA has established an e-mail address where an applicant can send

questions about the content of the guidance, such as requesting

clarification of information in the guidance or requesting guidance on

the reporting category of particular change it wants to implement. The

e-mail address is: [email protected].

This guidance document contains collections of information that

require clearance by the Office of Management

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and Budget (OMB) under the Paperwork Reduction Act of 1995. In a notice

published in the Federal Register (64 FR 59776; November 3, 1999), FDA

announced that this collection of information has been submitted to OMB

for emergency processing. This notice also solicited comments on the

collection of information. An agency may not conduct or sponsor, and a

person is not required to respond to, a collection of information

unless a currently valid OMB control number has been displayed.

Interested persons may, at any time, submit to the Dockets

Management Branch (address above) written comments on the guidance. 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 guidance and

received comments may be seen in the office above between 9 a.m. and 4

p.m., Monday through Friday.

Dated: November 16, 1999.

Margaret M. Dotzel,

Acting Associate Commissioner for Policy.

[FR Doc. 99-30481 Filed 11-18-99; 1:55 pm]

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