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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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`NDA 020592 S-060 S-061
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` NDA 021086 S-038 S-039
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`SUPPLEMENT APPROVAL
`RELEASE REMS REQUIREMENT
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`
`Eli Lilly and Company
`Attention: Kevin Sheehan, MS, Pharm.D.
`Manager, Global Regulatory Affairs, US
`Lilly Corporate Center
`
`Indianapolis, IN 46285
`
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`Dear Dr. Sheehan:
`
`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received March
`15, 2011 (S-061, S-039) and March 16, 2011 (S-060, S-038), submitted pursuant to section
`505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Zyprexa (olanzapine)
`Tablets 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg, and Zyprexa Zydis (olanzapine) Orally
`Disintegrating Tablets 5 mg, 10 mg, 15 mg, and 20 mg.
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`S-060 and S-038
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`We acknowledge receipt of your amendments to S-060 and S-038 dated May 31, 2011.
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`We also refer to our letter dated February 14, 2011, notifying you, under Section 505(o)(4) of the
`FDCA, of new safety information that we believe should be included in the labeling for Zyprexa
`(olanzapine) Tablets and Zyprexa Zydis (olanzapine) Orally Disintegrating Tablets. This
`information pertains to patient survey results that showed that patients did not understand the
`most important safety risks associated with the use of Zyprexa (olanzapine) Tablets and Zyprexa
`Zydis (olanzapine) Orally Disintegrating Tablets.
`
`These supplemental new drug applications provide for revisions to the Medication Guide for
`Zyprexa (olanzapine) Tablets and Zyprexa Zydis (olanzapine) Orally Disintegrating
`Tablets, consistent with our letter dated February 14, 2011.
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`We have completed our review of these supplemental 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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`
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`Reference ID: 2963544
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`

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`NDA 020592 S-060 S-061
`NDA 021086 S-038 S-039
`Page 2
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`S-061 and S-039
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`We acknowledge receipt of your risk evaluation and mitigation strategy (REMS) assessment
`dated September 17, 2010.
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`These supplemental new drug applications propose to eliminate the requirement for the approved
`risk evaluation and mitigation strategy (REMS) for Zyprexa (olanzapine) Tablets and Zyprexa
`Zydis (olanzapine) Orally Disintegrating Tablets.
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`We have completed our review of these supplemental applications. They are approved, effective
`on the date of this letter.
`
`
`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
`
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`The REMS for Zyprexa (olanzapine) Tablets and Zyprexa Zydis (olanzapine) Orally
`Disintegrating Tablets was originally approved on March 19, 2009 and a REMS modification
`was approved on December 4, 2009. The REMS consists of a Medication Guide and a timetable
`for submission of assessments of the REMS.
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`You propose that FDA no longer require a REMS for Zyprexa (olanzapine) Tablets and Zyprexa
`Zydis (olanzapine) Orally Disintegrating Tablets.
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`We have determined that maintaining the Medication Guide as part of the approved labeling is
`adequate to address the serious and significant public health concern and meets the standard in
`21 CFR 208.1. Therefore, it is no longer necessary to include the Medication Guide as an
`element of the approved REMS to ensure that the benefits of Zyprexa (olanzapine) Tablets and
`Zyprexa Zydis (olanzapine) Orally Disintegrating Tablets outweigh their risks.
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`Therefore, we agree with your proposal and a REMS for Zyprexa (olanzapine) Tablets and
`Zyprexa Zydis (olanzapine) Orally Disintegrating Tablets is no longer required.
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`We remind you that the Medication Guide will continue to be part of the approved labeling in
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`accordance with 21 CFR 208.
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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, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert, Medication
`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`
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`Reference ID: 2963544
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`

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`NDA 020592 S-060 S-061
`NDA 021086 S-038 S-039
`Page 3
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
`supplemental application, as well as annual reportable changes and annotate each change. To
`facilitate review of your submission, provide a highlighted or marked-up copy that shows all
`changes, as well as a clean Microsoft Word version. The marked-up copy should provide
`appropriate annotations, including supplement number(s) and annual report date(s).
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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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`If you have any questions, contact Keith Kiedrow, Pharm.D., Senior Regulatory Project
`Manager, at (301) 796-1924.
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`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Thomas Laughren, M.D.
`Director
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`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 2963544
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`

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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/
`----------------------------------------------------
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`THOMAS P LAUGHREN
`06/21/2011
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`Reference ID: 2963544
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`