Document ID: FDA-2015-D-1378-0001
Agency: fda
Document Type: Notice
Title: Bioequivalence Recommendations for Clozapine Orally Disintegrating
Tablets/Oral; Draft Guidance for Industry; Availability
Posted Date: 2015-05-06T04:00Z

[Federal Register Volume 80, Number 87 (Wednesday, May 6, 2015)]
[Notices]
[Pages 26063-26064]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-10478]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-1378]

Bioequivalence Recommendations for Clozapine Orally 
Disintegrating Tablets/Oral; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Bioequivalence 
Recommendations for Clozapine,'' for the orally disintegrating tablets 
(ODTs). The recommendations provide specific guidance on the design of 
bioequivalence (BE) studies to support abbreviated new drug 
applications (ANDAs) for clozapine ODTs.

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 the 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by July 6, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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section for electronic access to the draft guidance documents.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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: Xiaoqiu Tang, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4730, Silver Spring, MD 20993-0002, 301-
796-5850.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of June 11, 2010 (75 FR 33311), FDA 
announced the availability of a guidance for industry, ``Bioequivalence 
Recommendations for Specific Products,'' which explained the process 
that would be used to make product-specific BE recommendations 
available to the public on FDA's Web site at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. As 
described in that guidance, FDA adopted this process as a means to 
develop and disseminate product-specific BE recommendations and provide 
a meaningful opportunity for the public to consider and comment on 
those recommendations. This notice announces the availability of one 
draft BE recommendation for clozapine ODTs.
    Clozapine tablets, marketed under the name CLOZARIL, are the 
subject of new drug application (NDA) 19-758, held by Novartis 
Pharmaceuticals Corporation and approved by FDA on September 26, 1989. 
FazaClo ODTs were approved by FDA on February 19, 2004, under NDA 21-
590, currently held by Jazz Pharmaceuticals III International LTD, 
based upon a finding that FazaClo ODTs were bioequivalent to CLOZARIL 
immediate-release tablets. FazaClo ODTs are available as yellow, orally 
disintegrating tablets of 12.5, 25, 100, 150, and 200 \1\ milligrams 
(mg) of clozapine for oral administration without water. They are 
formulated to disintegrate once exposed to saliva and then are easily 
swallowed.
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    \1\ FDA approved the supplemental NDA for the 150 and 200 mg 
strengths on July 9, 2010.
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    In June 2005, FDA published a guidance for industry entitled 
``Clozapine Tablets: In Vivo Bioequivalence and In Vitro Dissolution 
Testing'' (Clozapine Guidance) (70 FR 35447, June 20, 2005), which 
replaced a 1996 product-specific bioequivalence guidance for clozapine 
tablets. The 2005 Clozapine Guidance recommends that ANDA applicants 
employ multiple-dose, steady-state studies to evaluate the

[[Page 26064]]

bioequivalence of clozapine products.\2\ FDA recommends that such 
studies be performed only in patients who have not responded well to 
standard antipsychotic drug treatment and who have been receiving a 
maintenance dose of an approved clozapine product for at least 3 
months. FDA is now issuing a draft guidance for industry on BE 
recommendations for generic clozapine that applies specifically to the 
ODTs.
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    \2\ The formatting of this guidance was updated in March 2011, 
but the content is unchanged. The March 2011 version is available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM249219.pdf.
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    Beckloff Associates, Inc., filed a citizen petition in December 
2007, a citizen petition supplement in February 2009, and a second 
citizen petition in November 2010, requesting that FDA impose certain 
requirements for bioequivalence testing for ANDAs referencing FazaClo 
(clozapine) ODTs and modify the Clozapine Guidance (Docket Nos. FDA-
2007-P-0188 and FDA-2010-P-0574). FDA is denying these petitions today.
    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 current thinking of FDA on bioequivalence 
recommendations for clozapine. It does not establish any rights for any 
person and is not binding on FDA or the public. You can use an 
alternative approach if it 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. Electronic Access

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

    Dated: April 30, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-10478 Filed 5-5-15; 8:45 am]
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