03-8010. Draft Guidance for Industry: Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action; Availability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The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action.” This draft document provides recommendations to applicants planning product quality studies to document bioavailability (BA) or bioequivalence (BE) in support of new drug applications (NDAs), or abbreviated new drug applications (ANDAs) for locally acting drugs in nasal aerosols (metered-dose inhalers) and nasal sprays (metered-dose spray pumps). The draft guidance was originally issued for comment on June 24, 1999. Since many substantive changes have been made to the guidance, it is being reissued for comment as a level 1 draft guidance.

DATES:

Submit written or electronic comments on the draft guidance by July 2, 2003. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the draft guidance for industry to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane,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 Submit written comments on the draft guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.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

Wallace P. Adams, Center for Drug Evaluation and Research (HFD-350), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-594-5651.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action.” This draft guidance provides recommendations to applicants planning product quality studies to document BA or BE in support of NDAs or ANDAs for locally acting drugs in nasal aerosols and nasal sprays. This guidance addresses BA and BE studies of prescription corticosteroids, antihistamines, anticholinergic drug products, and the over-the-counter (OTC) mast-cell stabilizer cromolyn sodium. The guidance does not address studies of nasal sprays included in applicable OTC monographs or studies of: (1) Metered-dose products intended to deliver drugs systemically via the nasal route, or (2) drugs in nasal nonmetered dose atomizer (squeeze) bottles that require premarket approval.

Because many substantive changes were made to the guidance after it issued in 1999, the guidance is being reissued at this time for comment as a level 1 draft guidance. We encourage applicants to submit any evidence that supports or refutes the approaches outlined in this guidance to the docket number given in brackets in the heading of this document.

The changes made were based on the following: (1) Public comments submitted to the original docket, (2) the outcome of April 2000 and July 2001 meetings of the Orally Inhaled and Nasal Drug Products Subcommittee of the FDA Advisory Committee for Pharmaceutical Science (ACPS), (3) a July 2001 meeting of the ACPS, and (4) internal discussions within the Center for Drug Evaluation and Research. Changes include reduction in the recommended extent of in vitro testing, elimination of two of the three options for rhinitis study design, and elimination of the recommendation to demonstrate a dose-response relationship from the recommended rhinitis study design (traditional 2-week study). The latter two changes are based on ACPS recommendations. A section on reserve samples for BA and BE testing has also been added. The statistical information that was previously part of the original draft has now been consolidated into appendices that will be published at a later date.

This level 1 draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency's current thinking on BA and BE product quality information related to nasal inhalation aerosols and nasal metered-dose spray pumps. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. Alternative approaches to documentation of BA and BE may be used if such approaches satisfy the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit to the Dockets Management Branch written or electronic comments regarding this document. Submit a single copy of electronic comments to http://www.fda.gov/​dockets/​ecomments or two hard copies of any written comments, except that individuals may submit one hard copy. Comments are to be indentified with the docket number found in brackets in the heading of this document. The draft guidance and received comments may be seen 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 either http://www.fda.gov/​cder/​guidance/​index.htm or http://www.fda.gov/​ohrms/​dockets/​default.htm.

Dated: March 25, 2003.

Jeffrey Shuren,

Assistant Commissioner for Policy.