[Federal Register Volume 80, Number 148 (Monday, August 3, 2015)]
[Notices]
[Pages 46019-46020]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-18968]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-1997-D-0187]


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Classification System Class 1 and 3 Drugs; Draft Guidance for Industry; 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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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the availability of a draft guidance for industry entitled 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 This draft guidance has been developed to 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 The draft guidance is intended to define when a 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substances that meet the criteria in this draft guidance.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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by October 2, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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.

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.

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.

[[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.

    Dated: July 29, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-18968 Filed 7-31-15; 8:45 am]
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