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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 201280/S-006
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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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` Boehringer Ingelheim Pharmaceuticals, Inc.
` Attention: Chung Lee-Sogaard, Ph.D.
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` Associate Director, Drug Regulatory Affairs
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` 900 Ridgebury Road, P.O. Box 368
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` Ridgefield, CT 06877
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`Dear Dr. Lee-Sogaard:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received June 14,
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`2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
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`Tradjenta (linagliptin) tablets, 5 mg.
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`We acknowledge receipt of your amendments dated August 20 and October 17, 2012, and March
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`1 and May 21, 2013. The submission dated May 21, 2013, includes the agreed-upon carton and
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`container labeling. We also acknowledge receipt of your email dated June 11, 2013, that
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`includes the agreed-upon package insert and Medication Guide.
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`This “Prior Approval” supplemental new drug application proposed to update the Tradjenta
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`package insert with information regarding pancreatitis based on postmarketing safety reports. In
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`an email dated January 29, 2013, we also required that you submit a Medication Guide to address
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`this safety issue.
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`“SPL Standard for Content of Labeling Technical Qs and As at
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`Reference ID: 3326783
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` NDA 201280/S-006
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` Page 2
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
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` 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 that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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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
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`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
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`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;
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`instructions are provided on page 2 of the form. For more information about submission of
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`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
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`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`Reference ID: 3326783
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` NDA 201280/S-006
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` Page 3
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` REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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`We request that for a period of two years, you submit all cases of hemorrhagic and/or
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`necrotizing pancreatitis and all cases of suspected or confirmed reports of acute pancreatitis with
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`an outcome of death reported with Tradjenta as 15-day alert reports, and that you provide
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`detailed analyses of clinical trial and post-marketing reports of pancreatitis, including
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`hemorrhagic and/or necrotizing pancreatitis, as adverse events of special interest in your periodic
`safety update reports (PSURs). These analyses should show cumulative data relative to the date
`of approval of Tradjenta as well as relative to the prior PSUR. Medical literature reviews for case
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`reports/case series of pancreatitis with Tradjenta should also be provided in the PSURs.
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`If you have any questions, call Raymond Chiang, Regulatory Project Manager, at (301) 796­
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`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
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`Division of Metabolism and Endocrinology Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`Package Insert
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`Medication Guide
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`Carton and Container Labeling
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`Reference ID: 3326783
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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
`06/18/2013
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`Reference ID: 3326783
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