[Federal Register: June 20, 2005 (Volume 70, Number 117)]
[Notices]
[Page 35447-35448]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr20jn05-55]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2003D-0549]
Guidance for Industry on Clozapine Tablets: In Vivo
Bioequivalence and In Vitro Dissolution Testing; 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 guidance for industry entitled ``Clozapine Tablets:
In Vivo Bioequivalence and In Vitro Dissolution Testing.'' The guidance
was originally published in November 1996. However, because of
potentially significant adverse effects seen in healthy subjects who
had not previously used clozapine, FDA proposed a revision to the
guidance in a draft published in December 2003. FDA did not receive
comments on the draft guidance during the comment period. This final
version of the 2003 draft guidance includes a change in the recommended
patient population as well as other minor changes that are based on
current information available to FDA.
DATES: Submit written or electronic comments on agency guidances at any
time.
ADDRESSES: Submit written requests for single copies of this 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 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments.
See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Lizzie Sanchez, Center for Drug
Evaluation and Research (HFD-650), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-5847.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Clozapine Tablets: In Vivo Bioequivalence and In Vitro
Dissolution Testing.'' This guidance is being issued because of
necessary changes to recommendations provided in a previous guidance on
the same topic that published in November 1996. In the Federal Register
of December 30, 2003 (68 FR 75262), FDA published a document that
proposed revisions to the 1996 guidance and that provided information
to the pharmaceutical industry regarding the design of bioequivalence
studies for generic clozapine products.
In the 1996 guidance, FDA recommended that doses of one-half of a
25 milligram clozapine tablet be administered to healthy subjects in
bioequivalence studies for generic clozapine products. The guidance
also provided an option for conducting studies in the appropriate
patient population. However, in the 2003 draft guidance, FDA proposed
that such studies not be conducted in healthy subjects because a high
number of healthy subjects experienced serious adverse effects such as
hypotension, bradycardia, syncope, and asystole during clozapine
bioequivalence studies. FDA did not receive comments on the 2003 draft
guidance during the comment period.
This final version of the 2003 draft guidance has been further
revised to provide recommendations describing the use of an appropriate
patient population that is already stable on a dose of clozapine. The
use of healthy subjects who had not previously used clozapine is no
longer recommended in this final version of the guidance, which will
ensure the safety of subjects in bioequivalence studies on clozapine.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
agency's current thinking on clozapine tablets: in vivo and in vitro
dissolution testing. It does not create or confer any rights for
[[Page 35448]]
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 regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified 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.
III. Electronic Access
Persons with access to the Internet may obtain the document at
either http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm.
Dated: June 9, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-12039 Filed 6-17-05; 8:45 am]
BILLING CODE 4160-01-S