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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`020592Orig1s040s041
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`APPROVAL LETTER
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`NDA 020592/S-040/S-041
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`Eli Lilly and Company
`Attention: Gregory T. Brophy, Ph.D.
`Director, U.S. Regulatory Affairs
`Lilly Corporate Center
`Indianapolis, IN 46285
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`Dear Dr. Brophy:
`
`Please refer to your supplemental new drug applications dated October 30, 2006, and received on
`October 31, 2006, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`for Zyprexa (olanzapine) Tablets, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg.
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`We acknowledge receipt of your submissions dated September 19, 2008, December 1, 2008,
`December 19, 2008, May 5, 2009, September 18, 2009 and October 13, 2009.
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`The September 19, 2008 submission constituted a complete response to our August 1, 2008
`action letter.
`
`These supplemental new drug applications provide for the use of Zyprexa (olanzapine) for the
`treatment of manic or mixed episodes of bipolar I disorder and schizophrenia in adolescents, a
`proposed modification to the approved Risk Evaluation and Mitigation Strategy (REMS), and a
`REMS assessment.
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`We have completed our review of these applications, as amended. They are approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`On October 13, 2009, you submitted a proposed modification and an assessment of your Risk
`Evaluation and Mitigation Strategy (REMS), originally approved on March 19, 2009. The
`proposed modified REMS contains a revised Medication Guide which includes new indications
`for the use of Zyprexa in treating manic or mixed episodes of bipolar I disorder and
`schizophrenia in adolescents ages 13 to 17, and a timetable for submission of assessments
`revised to specify the dates the assessments are due and that the assessments will be received by
`FDA on or before the due dates.
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`

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`NDA 020592/S-040/S-041
`Page 2
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`Your proposed modified REMS, appended to this letter, is approved. The REMS consists of the
`Medication Guide and a timetable for submission of assessments.
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`There are no changes to the REMS assessment plan.
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`The requirements for assessments of an approved REMS under section 505-1(g)(3) include, in
`section 505-1(g)(3)(B) and (C), requirements for information on the status of any post-approval
`study or clinical trial required under section 505(o) or otherwise undertaken to investigate a
`safety issue. You can satisfy these requirements in your REMS assessments by referring to
`relevant information included in the most recent annual report required under section 506B and
`21 CFR 601.70 and including any updates to the status information since the annual report was
`prepared. Failure to comply with the REMS assessment provisions in 505-1(g) could result in
`enforcement action.
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`We remind you that in addition to the assessments submitted according to the timetable included
`in the approved REMS, you must submit a REMS assessment and may propose a modification to
`the approved REMS when you submit a supplemental application for a new indication for use as
`described in section 505-1(g)(2)(A) of FDCA.
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`Prominently identify submissions containing the REMS assessments or proposed modifications
`of the REMS with the following wording in bold capital letters at the top of the first page of the
`submission:
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, please submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm that is
`identical to the enclosed agreed-upon labeling text. Upon receipt, we will transmit that version
`to the National Library of Medicine for public dissemination. For administrative purposes,
`please designate this submission, “SPL for approved NDA 20-592/S-040/S-041.”
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
`FOR NDA 20592
`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`NDA 20592 REMS ASSESSMENT
`NEW SUPPLEMENT FOR NDA 20592
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
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`NDA 020592/S-040/S-041
`Page 3
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`We request that the revised labeling approved today be available on your website within 10 days
`of receipt of this letter.
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` LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and to the following address:
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`MedWatch
`Food and Drug Administration
`5600 Fishers Lane, Room 12B05
`Rockville, MD 20857
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see www.fda.gov/cder/ddmac.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA (21
`CFR 314.80 and 314.81).
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`MEDWATCH-TO-MANUFACTURER PROGRAM
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`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at
`http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm.
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`

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`NDA 020592/S-040/S-041
`Page 4
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`If you have any questions, please call Kimberly Updegraff, M.S., Senior Regulatory Project
`Manager, at (301) 796-2201.
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`Sincerely,
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`{See appended electronic signature page}
`
`Thomas Laughren, M.D.
`Director
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosures
`Content of Labeling
`REMS
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`Application
`Type/Number
`--------------------
`NDA-20592
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`Submission
`Type/Number
`--------------------
`SUPPL-40
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`NDA-20592
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`SUPPL-41
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`Submitter Name
`
`Product Name
`
`------------------------------------------
`--------------------
`ELI LILLY AND CO ZYPREXA(OLANZAPINE) ORAL
`TABS 2.5MG/5MG/
`ELI LILLY AND CO ZYPREXA(OLANZAPINE) ORAL
`TABS 2.5MG/5MG/
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`THOMAS P LAUGHREN
`12/04/2009
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