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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021995/ S-034
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` NDA 022044/ S-035
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` NDA 202270/ S-010
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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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` Merck Sharp & Dohme Corp.
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` Attention: Lou Ann Eader, Ph.D.
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` Director, Worldwide Regulatory Affairs
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` 351 N. Sumneytown Pike
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` P. O. Box 1000, UG2CD-48
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` North Wales, PA 19454-1099
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` Dear Dr. Eader:
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` Please refer to your Supplemental New Drug Applications (sNDAs) dated and received
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` June 8, 2015, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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` (FDCA) for Januvia (sitagliptin) tablets, Janumet (sitagliptin and metformin HCl) tablets, and
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` Janumet XR (sitagliptin and metformin HCl extended-release) tablets.
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` We acknowledge receipt of your amendments dated July 31 and August 18, 2015.
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` We also refer to our letter dated April 24, 2015, notifying you, under Section 505(o)(4) of the
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` FDCA, of new safety information that we believe should be included in the labeling for
` dipeptidyl peptidase-4 (DPP-4) inhibitor products. This information pertains to the risk of joint
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` pain, sometimes severe and disabling, in patients treated with DPP-4 inhibitors.
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` These sNDAs provide for revisions to the labeling to address the risk of arthralgia, with the use
` of DPP-4 inhibitors, consistent with our April 24, 2015, letter.
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` APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
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`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
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`upon labeling text.
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
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`201.57(d)(8) regarding the length of Highlights of prescribing information.
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`Reference ID: 3812569
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` NDA 021995/ S-034
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` NDA 022044/ S-035
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` NDA 202270/ S-010
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` Page 2
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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
` 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
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible via publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
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`supplements for which FDA has not yet issued an action letter, with the content of labeling
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`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
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`supplemental application, as well as annual reportable changes, and annotate each change. To
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`facilitate review of your submission, provide a highlighted or marked-up copy that shows all
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`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
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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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`Reference ID: 3812569
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` NDA 021995/ S-034
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` NDA 022044/ S-035
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` NDA 202270/ S-010
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` Page 3
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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
`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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` OPDP Regulatory Project Manager
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` Food and Drug Administration
` Center for Drug Evaluation and Research
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` Office of Prescription Drug Promotion (OPDP)
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` 5901-B Ammendale Road
` Beltsville, MD 20705-1266
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` Alternatively, you may submit a request for advisory comments electronically in eCTD format.
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` For more information about submitting promotional materials in eCTD format, see the draft
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` Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`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
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`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
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`electronically in eCTD format. For more information about submitting promotional materials in
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`eCTD format, see the draft Guidance for Industry (available at:
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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` CM443702.pdf ).
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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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`Reference ID: 3812569
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` NDA 021995/ S-034
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` NDA 022044/ S-035
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` NDA 202270/ S-010
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` Page 4
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`If you have any questions, call Richard Whitehead, M.S., Regulatory Project Manager, at (301)
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`796-4945.
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`Sincerely,
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`{See appended electronic signature page}
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`Jennifer Rodriguez Pippins, M.D., M.P.H.
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`Deputy Director for Safety
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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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`ENCLOSURE:
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`Content of Labeling
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`Reference ID: 3812569
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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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`JENNIFER R PIPPINS
`08/28/2015
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`Reference ID: 3812569
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