03-28045. Draft Guidance for Industry on Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling and Assessment; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Powder Blends and Finished Dosage Units—Stratified In-Process Dosage Unit Sampling and Assessment.” The draft guidance is intended to provide recommendations to manufacturers of human drug products on how to develop a single control procedure to demonstrate the adequacy of mix to ensure uniformity and homogeneity of in-process powder blends and finished dosage units.

DATES:

Submit written or electronic comments on the draft guidance by March 8, 2004. General comments on agency draft guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the draft guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. 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 Submit written comments on the draft guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

Jon Clark, Center for Drug Evaluation and Research (HFD-003), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-5103.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Powder Blends and Finished Dosage Units—Stratified In-Process Dosage Unit Sampling and Assessment.” The draft guidance is intended to respond to industry concerns regarding FDA policies on demonstrating the adequacy of in-process powder mixing and uniform content in finished products under 21 CFR 211.110(a)(3).

In the Federal Register of August 27, 1999 (64 FR 46917), FDA published notice of the availability of a draft guidance for industry on blend uniformity analysis. Although FDA subsequently withdrew the draft guidance on May 17, 2002 (67 FR 35120), comments submitted on the draft guidance led to the formation of the Blend Uniformity Working Group (BUWG). The BUWG, which includes representatives from the agency, industry, and academia, conducted a public meeting on September 7 and 8, 2000, and developed a draft recommendation, “The Use of Stratified Sampling of Blend and Dosage Units to Demonstrate Adequacy of Mix for Powder Blends,” which included the consensus reached by participants in this workshop. The PDA Journal of Pharmaceutical Science and Technology published the recommendation (March/April 2003, pp. 59-74). This draft guidance reflects CDER's effort to incorporate the recommendation into regulatory policy.

Stratified sampling is the selection of in-process dosage unit samples to specifically target locations in the compression/filling operation that have the greatest potential to yield extreme highs and lows in test results. The test results are used to monitor the manufacturing process output that is most responsible for causing finished product variability. These test results can be used to develop a single control procedure to ensure adequate powder mix and uniform content in finished products.

This draft guidance is being issued consistent with FDAs good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency's current thinking on “Powder Blends and Finished Dosage Units—Stratified In-Process Dosage Unit Sampling and Assessment.” 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 submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments on the draft guidance. Two copies of mailed 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 draft 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 document at either http://www.fda.gov/​cder/​guidance/​index.htm or http://www.fda.gov/​ohrms/​dockets/​default.htm.

Dated: October 31, 2003.

Jeffrey Shuren,

Assistant Commissioner for Policy.