Food and Drug Administration, HHS.
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 FDA did not receive comments on the draft guidance during the comment period. This final version of the 2003 draft guidance includes a change in the recommended patient population as well as other minor changes that are based on current information available to FDA.
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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://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.Start Further Info
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.End Further Info End Preamble Start Supplemental Information
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 Start Printed Page 35448or 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.
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 AccessStart Signature
Dated: June 9, 2005.
Assistant Commissioner for Policy.
[FR Doc. 05-12039 Filed 6-17-05; 8:45 am]
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