80 FR 26063 - Bioequivalence Recommendations for Clozapine Orally Disintegrating Tablets/Oral; Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 87 (May 6, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 87 (May 6, 2015)
| Page Range | 26063-26064 | |
| FR Document | 2015-10478 |
[Federal Register Volume 80, Number 87 (Wednesday, May 6, 2015)] [Notices] [Pages 26063-26064] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-10478] ----------------------------------------------------------------------- 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[Docket No. FDA-2015-D-1378] Bioequivalence Recommendations for Clozapine Orally Disintegrating Tablets/Oral; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS.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. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Bioequivalence Recommendations for Clozapine,'' for the orally disintegrating tablets (ODTs).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comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on the draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by July 6, 2015. ADDRESSES: Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th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 See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance documents. Submit electronic comments on the draft guidance to http://www.regulations.gov.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. --------------------------------------------------------------------------- \1\ FDA approved the supplemental NDA for the 150 and 200 mg strengths on July 9, 2010. --------------------------------------------------------------------------- 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. --------------------------------------------------------------------------- \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. --------------------------------------------------------------------------- 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] BILLING CODE 4164-01-P
![Federal Register / Vol. 80, No. 87 / Wednesday, May 6, 2015 / Notices 26063
Veterinary Medicine (CVM), as part of will be posted to the docket at http:// Administration, 5630 Fishers Lane, Rm.
an NADA or ANADA, respectively. www.regulations.gov. 1061, Rockville, MD 20852.
CVM encourages sponsors to submit
data for review at the most appropriate V. Electronic Access FOR FURTHER INFORMATION CONTACT:
and productive times in the drug Persons with access to the Internet Xiaoqiu Tang, Center for Drug
development process. Rather than may obtain the guidance at either Evaluation and Research, Food and
submitting all data for review as part of http://www.fda.gov/AnimalVeterinary/ Drug Administration, 10903 New
a complete application, we have found GuidanceComplianceEnforcement/ Hampshire Ave., Bldg. 75, Rm. 4730,
that the submission of data supporting GuidanceforIndustry/default.htm or Silver Spring, MD 20993–0002, 301–
discrete technical sections during the http://www.regulations.gov. 796–5850.
investigational phase of the new animal Dated: April 30, 2015. SUPPLEMENTARY INFORMATION:
drug is the most appropriate and Leslie Kux,
productive. This ‘‘phased review’’ of I. Background
Associate Commissioner for Policy.
data submissions has created
[FR Doc. 2015–10480 Filed 5–5–15; 8:45 am] In the Federal Register of June 11,
efficiencies for CVM and the animal
BILLING CODE 4164–01–P 2010 (75 FR 33311), FDA announced the
pharmaceutical industry. These
increased efficiencies have facilitated availability of a guidance for industry,
the approval of both pioneer and generic ‘‘Bioequivalence Recommendations for
DEPARTMENT OF HEALTH AND Specific Products,’’ which explained the
new animal drugs.
This guidance defines what an HUMAN SERVICES process that would be used to make
administrative (A)NADA is, defines and product-specific BE recommendations
Food and Drug Administration available to the public on FDA’s Web
describes the phased review process,
and briefly discusses how sponsors [Docket No. FDA–2015–D–1378] site at http://www.fda.gov/Drugs/
should submit an administrative GuidanceComplianceRegulatory
(A)NADA and the time frame for review. Bioequivalence Recommendations for Information/Guidances/default.htm. As
Clozapine Orally Disintegrating described in that guidance, FDA
II. Significance of Guidance Tablets/Oral; Draft Guidance for adopted this process as a means to
This level 1 guidance is being issued Industry; Availability develop and disseminate product-
consistent with FDA’s good guidance specific BE recommendations and
AGENCY: Food and Drug Administration,
practices regulation (21 CFR 10.115). provide a meaningful opportunity for
HHS.
The guidance represents the current the public to consider and comment on
thinking of FDA on Administrative ACTION: Notice. those recommendations. This notice
Applications and the Phased Review SUMMARY: The Food and Drug announces the availability of one draft
Process. It does establish any rights for Administration (FDA) is announcing the BE recommendation for clozapine
any person and is not binding on FDA availability of a draft guidance for ODTs.
or the public. You can use an alternative industry entitled ‘‘Bioequivalence Clozapine tablets, marketed under the
approach if it satisfies the requirements Recommendations for Clozapine,’’ for name CLOZARIL, are the subject of new
of the applicable statutes and the orally disintegrating tablets (ODTs). drug application (NDA) 19–758, held by
regulations. The recommendations provide specific Novartis Pharmaceuticals Corporation
III. Paperwork Reduction Act of 1995 guidance on the design of and approved by FDA on September 26,
bioequivalence (BE) studies to support 1989. FazaClo ODTs were approved by
This guidance refers to previously
abbreviated new drug applications FDA on February 19, 2004, under NDA
approved collections of information
(ANDAs) for clozapine ODTs. 21–590, currently held by Jazz
found in FDA regulations. These
collections of information are subject to DATES: Although you can comment on Pharmaceuticals III International LTD,
review by the Office of Management and any guidance at any time (see 21 CFR based upon a finding that FazaClo ODTs
Budget (OMB) under the Paperwork 10.115(g)(5)), to ensure that the Agency were bioequivalent to CLOZARIL
Reduction Act of 1995 (44 U.S.C. 3501– considers your comment on the draft immediate-release tablets. FazaClo
3520). The collections of information in guidance before it begins work on the ODTs are available as yellow, orally
21 CFR part 514 have been approved final version of the guidance, submit disintegrating tablets of 12.5, 25, 100,
under OMB control number 0910–0032. either electronic or written comments 150, and 200 1 milligrams (mg) of
The collections of information in on the draft guidance by July 6, 2015. clozapine for oral administration
section 512(n)(1) of the FD&C Act have ADDRESSES: Submit written requests for without water. They are formulated to
been approved under OMB control single copies of the draft guidance to the disintegrate once exposed to saliva and
number 0910–0669. Division of Drug Information, Center for then are easily swallowed.
Drug Evaluation and Research, Food In June 2005, FDA published a
IV. Comments and Drug Administration, 10001 New guidance for industry entitled
Interested persons may submit either Hampshire Ave., Hillandale Building, ‘‘Clozapine Tablets: In Vivo
electronic comments regarding this 4th Floor, Silver Spring, MD 20993– Bioequivalence and In Vitro Dissolution
document to http://www.regulations.gov 0002. Send one self-addressed adhesive Testing’’ (Clozapine Guidance) (70 FR
or written comments to the Division of label to assist that office in processing 35447, June 20, 2005), which replaced a
Dockets Management (see ADDRESSES). It your requests. See the SUPPLEMENTARY 1996 product-specific bioequivalence
tkelley on DSK3SPTVN1PROD with NOTICES
is only necessary to send one set of INFORMATION section for electronic guidance for clozapine tablets. The 2005
comments. Identify comments with the access to the draft guidance documents. Clozapine Guidance recommends that
docket number found in brackets in the Submit electronic comments on the ANDA applicants employ multiple-
heading of this document. Received draft guidance to http:// dose, steady-state studies to evaluate the
comments may be seen in the Division www.regulations.gov. Submit written
of Dockets Management between 9 a.m. comments to the Division of Dockets 1 FDA approved the supplemental NDA for the
and 4 p.m., Monday through Friday, and Management (HFA–305), Food and Drug 150 and 200 mg strengths on July 9, 2010.
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![26064 Federal Register / Vol. 80, No. 87 / Wednesday, May 6, 2015 / Notices
bioequivalence of clozapine products.2 Dated: April 30, 2015. Place: National Institutes of Health; 6701
FDA recommends that such studies be Leslie Kux, Rockledge Drive; Bethesda, MD 20892;
performed only in patients who have (Virtual Meeting).
Associate Commissioner for Policy.
Contact Person: Jane A. Doussard-
not responded well to standard [FR Doc. 2015–10478 Filed 5–5–15; 8:45 am] Roosevelt, Ph.D.; Scientific Review Officer;
antipsychotic drug treatment and who BILLING CODE 4164–01–P Center for Scientific Review; National
have been receiving a maintenance dose Institutes of Health; 6701 Rockledge Drive,
of an approved clozapine product for at Room 3184, MSC 7848; Bethesda, MD 20892;
least 3 months. FDA is now issuing a DEPARTMENT OF HEALTH AND (301) 435–4445; doussarj@csr.nih.gov.
draft guidance for industry on BE HUMAN SERVICES Name of Committee: Brain Disorders and
recommendations for generic clozapine Clinical Neuroscience Integrated Review
National Institutes of Health Group; Pathophysiological Basis of Mental
that applies specifically to the ODTs.
Disorders and Addictions Study Section.
Beckloff Associates, Inc., filed a Center for Scientific Review; Notice of Date: June 3–4, 2015.
citizen petition in December 2007, a Closed Meetings Time: 8:00 a.m. to 5:00 p.m.
citizen petition supplement in February Agenda: To review and evaluate grant
2009, and a second citizen petition in Pursuant to section 10(d) of the applications.
Federal Advisory Committee Act, as Place: The Warwick Allerton Hotel; 701
November 2010, requesting that FDA North Michigan Avenue; Chicago, IL 60611.
impose certain requirements for amended (5 U.S.C. App.), notice is
Contact Person: Boris P Sokolov, Ph.D.;
bioequivalence testing for ANDAs hereby given of the following meetings. Scientific Review Officer; Center for
referencing FazaClo (clozapine) ODTs The meetings will be closed to the Scientific Review; National Institutes of
and modify the Clozapine Guidance public in accordance with the Health; 6701 Rockledge Drive, Room 5217A,
(Docket Nos. FDA–2007–P–0188 and provisions set forth in sections MSC 7846; Bethesda, MD 20892; 301–408–
552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 9115; bsokolov@csr.nih.gov.
FDA–2010–P–0574). FDA is denying
as amended. The grant applications and Name of Committee: Vascular and
these petitions today. Hematology Integrated Review Group;
the discussions could disclose
This draft guidance is being issued confidential trade secrets or commercial Molecular and Cellular Hematology Study
consistent with FDA’s good guidance Section.
property such as patentable material, Date: June 3–4, 2015.
practices regulation (21 CFR 10.115). and personal information concerning Time: 8:00 a.m. to 5:00 p.m.
The draft guidance, when finalized, will individuals associated with the grant Agenda: To review and evaluate grant
represent the current thinking of FDA applications, the disclosure of which applications.
on bioequivalence recommendations for would constitute a clearly unwarranted Place: Embassy Suites at the Chevy Chase
clozapine. It does not establish any invasion of personal privacy. Pavilion; 4300 Military Road NW.;
rights for any person and is not binding Washington, DC 20015.
Name of Committee: Center for Scientific Contact Person: Luis Espinoza, Ph.D.;
on FDA or the public. You can use an Review Special Emphasis Panel; PAR Panel:
alternative approach if it satisfies the Scientific Review Officer; Center for
Selected Topics and Transfusion Medicine. Scientific Review; National Institutes of
requirements of the applicable statutes Date: June 1–2, 2015. Health; 6701 Rockledge Drive, Room 6183,
and regulations. Time: 8:00 a.m. to 6:00 p.m. MSC 7804; Bethesda, MD 20892; 301–495–
Agenda: To review and evaluate grant 1213; espinozala@mail.nih.gov.
II. Comments applications. Name of Committee: Biobehavioral and
Place: National Institutes of Health; 6701 Behavioral Processes Integrated Review
Interested persons may submit either Rockledge Drive; Bethesda, MD 20892;
electronic comments regarding this Group; Cognition and Perception Study
(Virtual Meeting). Section.
document to http://www.regulations.gov Contact Person: Bukhtiar H Shah, DVM, Date: June 4–5, 2015.
or written comments to the Division of Ph.D.; Scientific Review Officer; Center for Time: 8:00 a.m. to 5:00 p.m.
Dockets Management (see ADDRESSES). It Scientific Review; National Institutes of Agenda: To review and evaluate grant
is only necessary to send one set of Health; 6701 Rockledge Drive, Room 4120, applications.
comments. Identify comments with the MSC 7802; Bethesda, MD 20892; 301–806– Place: Historic Inns of Annapolis; 58 State
7314; shahb@csr.nih.gov. Circle; Annapolis, MD 21401.
docket number found in brackets in the
heading of this document. Received Name of Committee: Center for Scientific Contact Person: Dana Jeffrey Plude, Ph.D.;
Review Special Emphasis Panel; PAR Panel: Scientific Review Officer; Center for
comments may be seen in the Division Selected Topics and Transfusion Medicine. Scientific Review; National Institutes of
of Dockets Management between 9 a.m. Date: June 1–2, 2015. Health; 6701 Rockledge Drive, Room 3176,
and 4 p.m., Monday through Friday, and Time: 8:00 a.m. to 6:00 p.m. MSC 7848; Bethesda, MD 20892; (301) 435–
will be posted to the docket at http:// Agenda: To review and evaluate grant 2309; pluded@csr.nih.gov.
www.regulations.gov. applications. Name of Committee: Biology of
Place: National Institutes of Health; 6701 Development and Aging Integrated Review
III. Electronic Access Rockledge Drive; Bethesda, MD 20892; Group; International and Cooperative
(Virtual Meeting). Projects—1 Study Section.
Persons with access to the Internet Contact Person: Katherine M Malinda, Date: June 4, 2015.
may obtain the documents at either Ph.D.; Scientific Review Officer; Center for Time: 8:00 a.m. to 6:00 p.m.
http://www.fda.gov/Drugs/ Scientific Review; National Institutes of Agenda: To review and evaluate grant
GuidanceCompliance Health; 6701 Rockledge Drive, Room 4140, applications.
RegulatoryInformation/Guidances/ MSC 7814; Bethesda, MD 20892; 301–435– Place: Villa Florence Hotel; 225 Powell
default.htm or http:// 0912; Katherine_Malinda@csr.nih.gov. Street; San Francisco, CA 94102.
Name of Committee: Center for Scientific Contact Person: Hilary D Sigmon, Ph.D.;
tkelley on DSK3SPTVN1PROD with NOTICES
www.regulations.gov.
Review Special Emphasis Panel; Child Scientific Review Officer; Center for
Psychopathology and Developmental Scientific Review; National Institutes of
2 The formatting of this guidance was updated in
Disabilities. Health; 6701 Rockledge Drive, Room 5222,
March 2011, but the content is unchanged. The MSC 7852; Bethesda, MD 20892; (301) 594–
March 2011 version is available at http:// Date: June 2–3, 2015.
www.fda.gov/downloads/Drugs/Guidance Time: 8:00 a.m. to 5:00 p.m. 6377; sigmonh@csr.nih.gov.
ComplianceRegulatoryInformation/Guidances/ Agenda: To review and evaluate grant Name of Committee: Risk, Prevention and
UCM249219.pdf. applications. Health Behavior Integrated Review Group;
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Document Created: 2015-12-16 07:40:50
Document Modified: 2015-12-16 07:40:50
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| 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. | |
| 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. | |
| FR Citation | 80 FR 26063 |
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