E9-16868. Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Substances; Availability

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 “ANDAs: Impurities in Drug Substances,” which is a revision of a guidance for industry of the same name that published in November 1999. The guidance provides recommendations for applicants on what chemistry, manufacturing, and controls (CMC) information to include regarding the reporting, identification, and qualification of impurities in drug substances produced by chemical synthesis when submitting original abbreviated new drug applications (ANDAs); drug master files (DMFs), including type II DMFs; and ANDA supplements for changes in the synthesis or processing of a drug substance.

DATES:

Submit written or electronic comments on agency guidances 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, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. 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.regulations.gov. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Lawrence Yu, Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276-9310.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a revised guidance for industry entitled “ANDAs: Impurities in Drug Substances.” The guidance provides revised recommendations on what CMC information to include regarding the reporting, identification, and qualification of impurities in drug substances produced by chemical synthesis when submitting: (1) Original ANDAs; (2) DMFs, including type II DMFs; and (3) ANDA supplements for changes in the synthesis or processing of a drug substance. The guidance also provides recommendations for establishing acceptance criteria for impurities in drug substances.

In November 1999, FDA published the first version of this guidance. In 2003, the International Conference on Harmonisation made changes to recommendations on impurities in drug substances for new drug applications in the guidance for industry entitled “Q3A Impurities in New Drug Substances” (Revision 1) (Q3A(R)). As a result of these changes, FDA began an effort to revise this guidance for ANDAs. FDA has revised the guidance to update information on listing impurities, setting acceptance criteria, and qualifying impurities (thresholds and procedures) in ANDAs to make it consistent with Q3A(R).

On January 31, 2005 (70 FR 4857), FDA announced the availability of the draft revision for public comment. The comment period closed on May 2, 2005. A number of comments were received, which the agency considered carefully as it began the process of finalizing the guidance.

This 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 impurities in drug substances for generic drugs. 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 an approach satisfies the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments regarding this document. 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 brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

III. Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information in 21 CFR part 314 have been approved under OMB Control No. 0910-0001.

IV. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm or http://www.regulations.gov.

Dated: July 7, 2009.

Jeffrey Shuren,

Associate Commissioner for Policy and Planning.