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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 022350/S-007
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Bristol-Myers Squibb Company
`Attention: Pamela J. Smith, M.D.
`Group Director, GRS
`P.O. Box 4000
`Princeton, NJ 08543
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`Dear Dr. Smith:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received May 19,
`2011, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Onglyza (saxagliptin) Tablets 2.5 mg and 5 mg.
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`We acknowledge receipt of your amendments dated November 4, 2011.
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`We also refer to our email dated August 4, 2011, requesting submission of a Medication Guide.
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`This “Prior Approval” supplemental new drug application provides for conversion of the
`approved patient package insert to a Medication Guide, revisions to the INDICATIONS AND
`USAGE, CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS sections of the
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`Highlights of Prescribing Information section and changes to the INDICATIONS AND
`USAGE, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, ADVERSE
`REACTIONS, and PATIENT COUNSELING INFORMATION sections of the Full
`Prescribing Information sections of the Onglyza package insert, with information regarding
`hypersensitivity reactions, including anaphylaxis and angioedema, and acute pancreatitis.
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`We have completed our review of this supplemental application, as amended. It is 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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`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 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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`Reference ID: 3044277
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` NDA 022350/S-007
`Page 2
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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` 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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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels or carton and immediate container labels submitted on November 4,
`2011, as soon as they are available, but no more than 30 days after they are printed.
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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
`Division of Drug Marketing, Advertising, and Communications
`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
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`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 Drug Marketing, Advertising, and Communications
`(DDMAC), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`Reference ID: 3044277
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` NDA 022350/S-007
`Page 3
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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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`It is no longer necessary to submit 15-day expedited reports for all postmarketing cases of
`pancreatitis, as requested in the July 31, 2009, approval letter for Onglyza. Instead, include in
`your Periodic Safety Update Reports (PSURs) for Onglyza a detailed analysis of postmarketing
`reports of pancreatitis and hypersensitivity reactions (including angioedema, anaphylaxis, and
`Stevens Johnson Syndrome). For these analyses, show cumulative data relative to the date of
`approval of Onglyza as well as relative to the prior PSUR.
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`If you have any questions, call Raymond Chiang, Regulatory Project Manager, at (301) 796-
`1940.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary H. Parks, M.D.
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`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Package Insert
`Medication Guide
`Container Label – 2.5mg, 30 tablet bottle
`Container Label – 2.5mg, 90 tablet bottle
`Container Label – 5mg, 30 tablet bottle
`Container Label – 5mg, 90 tablet bottle
`Container Label – 5mg, 500 tablet bottle
`Carton Label – 5mg, 28 tablet, contains 4 of the 7 tablet wallets (sample)
`Carton Label – 5mg, 100 tablet, 10 blister cards with 10 tablets each
`Container/Carton Label – 5mg, 7 tablet wallet (sample)
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`Reference ID: 3044277
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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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`MARY H PARKS
`11/15/2011
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`Reference ID: 3044277
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