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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 021462/S-029
`NDA 021462/S-030
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`NDA 021462/S-032
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Eli Lilly and Company
`Attention: Daniel R. Brady, Ph.D., RAC
`Senior Director
`Global Affairs - US
`Lilly Corporate Center
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`Indianapolis, Indiana 46285
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`Dear Dr. Brady:
`
`Please refer to your Supplemental New Drug Applications (sNDAs) S-029 and S-032, dated July
`16, 2010, received July 16, 2010, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Alimta, (pemetrexed disodium) sterile lyophilized powder, 500 mg vials
`& 100 mg vials.
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`We acknowledge receipt of your amendments to S-029 and S-032 dated October 20, 2010;
`January 10, 2011; April 8, 2011; May 10, 2011; September 20, 2011; September 23, 2011;
`October 13, 2011; November 03, 2011; November 14, 2011; and November 16, 2011.
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`The September 20, 2011 (S-032) and September 23, 2011 (S-029) submissions constituted a
`complete response to our May 16, 2011, action letter, respectively.
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`We also refer to your sNDA S-030 dated August 10, 2010, received August 10, 2010 submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Alimta,
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`(pemetrexed disodium) sterile lyophilized powder, 500 mg vials & 100 mg vials.
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`We acknowledge receipt of your amendments to S-030 dated July 20, 2011; August 3, 2011;
`October 18, 2011; November 14, 2011; and November 16, 2011.
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`S-029: This “Prior Approval” supplemental new drug application (S-029) provides for revisions
`to Highlights and Section 5.7 Third Space Fluid of the package insert, to include the effects of
`Alimta in patients with or without third space fluid.
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`S-030: This “Prior Approval” supplemental new drug application (S-030) provides for revisions
`to the package insert to include removal of the Recent Major Change of "Indications and Usage,
`Locally Advanced or Metastatic Nonsquamous Non-Small Lung Cancer - Maintenance (1.2)
`(07/2009)" due to exhaustion of the 1 year requirement; revision of the Table of Contents to be
`consistent with the Full Prescribing Information; creation of a new subsection under Section 6.0
`titled “Additional Clinical Trials Experience” to add information regarding “sepsis;” and
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`Reference ID: 3047050
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`

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` NDA 021462/S-029
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` NDA 021462/S-030
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` NDA 021462/S-032
`Page 2
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`revision of Section 6.2 Post-Marketing Experience and of the patient package insert to include
`bullous conditions.
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`S-032: This “Prior Approval” supplemental new drug application (S-032) provides for revisions
`to the Highlights, 5.4 Use of Non-Steroidal Anti-Inflammatory Drugs with Mild to Moderate
`Renal Insufficiency, 7.1 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and 7.2
`Nephrotoxic Drugs sections of the package insert to include updated data concerning
`concomitant use of Alimta with non-steroidal anti-inflammatory drugs (NSAIDs).
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`We have completed our review of these three 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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`CONTENT OF LABELING
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`
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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 and patient
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`package insert), 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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`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 these
`supplemental applications, 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
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`appropriate annotations, including supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`
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`Reference ID: 3047050
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`

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` NDA 021462/S-029
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` NDA 021462/S-030
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` NDA 021462/S-032
`Page 3
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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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 the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Professional Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Division of Professional Promotion (DPP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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, call Deanne Varney, Regulatory Project Manager, at (301) 796-0297.
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`Sincerely,
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`{See appended electronic signature page}
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`Patricia Keegan, M.D.
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`Director
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`Division of Oncology Products 2
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`Office of Oncology and Hematology Products
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`Reference ID: 3047050
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`Amna Ibrahim, M.D.
`Deputy Director
`Division of Oncology Products 1
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
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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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`AMNA IBRAHIM
`11/18/2011
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`PATRICIA KEEGAN
`11/18/2011
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`Reference ID: 3047050
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