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Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs; Draft Guidance for Industry; Availability

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AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs.” This draft guidance has been developed to provide manufacturers with recommendations for submission of new drug applications (NDAs), investigational new drug applications (INDs), and/or abbreviated new drug applications (ANDAs), as appropriate, for immediate-release (IR) tablets and capsules that contain highly soluble drug substances. The draft guidance is intended to define when a standard release test and criteria may be used in lieu of extensive method development and specification-setting exercises. When final, this guidance will supersede the guidance for industry on “Dissolution Testing of Immediate Release Solid Oral Dosage Forms” (August 1997) for biopharmaceutics classification system (BCS) class 1 and 3 drug substances that meet the criteria in this draft guidance. For class 2 and 4 drug substances, applicants should still refer to the August 1997 guidance mentioned previously.

DATES:

Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by October 2, 2015.

ADDRESSES:

Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

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FOR FURTHER INFORMATION CONTACT:

Richard Lostritto, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, 301-796-1667.

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SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs.” Drug absorption from a solid dosage form after oral administration depends on the release of the drug substance from the drug product, the dissolution or solubilization of the drug under physiological conditions, and the permeation across the gastrointestinal membrane. NDAs and ANDAs submitted to FDA contain bioavailability (BA) or bioequivalence (BE) data and in vitro dissolution data that, together with chemistry, manufacturing, and controls (CMC) data, characterize the quality and performance of the drug product. In vitro dissolution data are generally obtained from batches that have been used in pivotal clinical and/or bioavailability studies and from other human studies conducted during product development. Knowledge about the solubility, permeability, dissolution, and pharmacokinetics of a drug product is considered when defining dissolution test specifications for the drug approval process.

The BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. The definitions of high and low solubility and high and low permeability are used as described in FDA's Biopharmaceutics Classification System (BCS) Guidance. The different classifications are:

Class 1: High Solubility—High Permeability Drugs

Class 2: Low Solubility—High Permeability Drugs

Class 3: High Solubility—Low Permeability Drugs

Class 4: Low Solubility—Low Permeability Drugs

This classification can be used as a basis for determining when in vivo bioavailability and bioequivalence studies are needed and can be used to determine when a successful in vivo-in vitro correlation (IVIVC) is likely. The BCS suggests that, for certain high solubility drugs, dissolution testing can be standardized or may not be needed. Owing to their high solubility, BCS class 1 and 3 drugs are considered to be relatively low risk regarding the impact of dissolution on performance, provided the in vitro performance meets or exceeds the recommendations discussed in the guidance.Start Printed Page 46020

This draft guidance establishes standard dissolution methodology and specifications that are appropriate for BCS class 1 and class 3 drugs. The availability of these standards will facilitate the rapid development of dissolution methodology and related specifications for these classes during drug development and application review.

This 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 Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 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 approach satisfies the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.

III. The Paperwork Reduction Act of 1995

This draft guidance refers to previously approved collections of information that 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 parts 312 and 314 have been approved under OMB control numbers 0910-0014 and 0910-0001, respectively.

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.

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Dated: July 29, 2015.

Leslie Kux,

Associate Commissioner for Policy.

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[FR Doc. 2015-18968 Filed 7-31-15; 8:45 am]

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