[Federal Register Volume 64, Number 225 (Tuesday, November 23, 1999)]
[Notices]
[Pages 65716-65717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-30481]


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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

[[Page 65717]]

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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