` NDA 201280/S-020
`
` NDA 201281/S-024
`
`
` NDA 206073/S-021
`
`
` NDA 208026/S-012
`
`
`
`
`
`SUPPLEMENT APPROVAL
`
`
`
`
`
`
` Boehringer Ingelheim Pharmaceuticals, Inc.
`
`
` Attention: Charles Mazzarella
` Director, Regulatory Affairs; and
`
`
` Madhuri Jerfy, M.S.
`
` Associate Director, Regulatory Affairs
`
`
` 900 Ridgebury Road, P.O. Box 368
`
` Ridgefield, CT 06877
`
`
` Dear Mr. Mazzarella and Ms. Jerfy:
`
` Please refer to your supplemental new drug applications (sNDAs) dated and received
`
`
`
`
`
`
` May 30, 2019 (NDA 201280) and June 6, 2019 (NDA 201281, NDA 206073, NDA
` 208026), and your amendments, submitted under section 505(b) and pursuant to
`
`
`
`
` section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Tradjenta
` (linagliptin) tablets, Jentadueto (linagliptin and metformin hydrochloride) tablets,
`
` Glyxambi (empagliflozin and linagliptin) tablets, and Jentadueto XR (linagliptin and
`
` metformin hydrochloride extended-release) tablets.
`
` These Prior Approval supplemental new drug applications provide for revisions to the
`
`
`
`
`
`
`
` prescribing information to include information based on Study 1218.74 entitled, A
`multicenter, international, randomized parallel group, double-blind trial to evaluate
`
`
`
` cardiovascular safety of linagliptin versus glimepiride in patients with T2DM at high
`
` cardiovascular risk. The CAROLINA trial.
`
` APPROVAL & LABELING
`
`We have completed our review of these applications, as amended. They are approved,
`
`
`
`
`
`
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`
`
`upon labeling.
`
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`
`
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`
`
`
`
`
`
`
`
`Reference ID: 4583067
`
`
`
`
`
`
`
`
` NDA 201280/S-020
`
` NDA 201281/S-024
`
` NDA 206073/S-021
`
`NDA 208026/S-012
`
` Page 2
`
`
` CONTENT OF LABELING
`
`
`
` 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
`
`
`
`
` FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`
`
`
`Prescribing Information 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.
`
`
`Information on submitting SPL files using eList may be found in the guidance for
`
`
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`
`
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`
`
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`
`
`
`
`
`changes for these NDAs, 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 Microsoft Word
`
`
`
`format, that includes the changes approved in this supplemental application, as well as
`
`annual reportable changes. To facilitate review of your submission(s), 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).
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`
`
`new active ingredients (which includes new salts and new fixed combinations), 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 in pediatric patients unless this requirement is waived, deferred,
`
`or inapplicable.
`
`
`
`Because none of these criteria apply to your applications, you are exempt from this
`
`requirement.
`
`
`
`
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`
` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`
`
`Reference ID: 4583067
`
`
`
`
`
`
` NDA 201280/S-020
`
` NDA 201281/S-024
`
` NDA 206073/S-021
`
`NDA 208026/S-012
`
` Page 3
`
`
` PROMOTIONAL MATERIALS
`
` 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 Prescribing Information to:
`
`
`
`OPDP Regulatory Project Manager
`
`Food and Drug Administration
`
`
`Center for Drug Evaluation and Research
`
`Office of Prescription Drug Promotion (OPDP)
`
`5901-B Ammendale Road
`
`Beltsville, MD 20705-1266
`
`
`
`
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD
`
`
`
`
`format. For more information about submitting promotional materials in eCTD format,
`
`
`
`see the draft guidance for industry Providing Regulatory Submissions in Electronic and
`
`Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
`
`Prescription Drugs.3
`
`
`
`
`You must submit final promotional materials and Prescribing Information, accompanied
`
`
`
`by a Form FDA 2253, at the time of initial dissemination or publication
`
`
`
`
`
`
`
`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
`
`
`
`
`
`Instructions for completing the form can be found at FDA.gov.5 For more information
`about submission of promotional materials to the Office of Prescription Drug Promotion
`
`
`(OPDP), see FDA.gov.6
`
`
`REPORTING REQUIREMENTS
`
`
` We remind you that you must comply with reporting requirements for an approved NDA
`
` (21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
` version of a guidance, check the FDA guidance web page at
`
` https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`
` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`
`
`Reference ID: 4583067
`
`
`
`
` NDA 201280/S-020
`
` NDA 201281/S-024
`
` NDA 206073/S-021
`
`NDA 208026/S-012
`
` Page 4
`
`
` If you have any questions, call Richard Whitehead, Regulatory Project Manager, at
`
` (301) 796-4945.
`
`
`
`
`
`
`
`
`
`Sincerely,
`
`
`
`{See appended electronic signature page}
`
`
`Patrick Archdeacon, M.D.
`
`
`
`Associate Director for Therapeutics (Acting)
`
`
`Division of Diabetes, Lipid Disorders, and Obesity
`Office of Cardiology, Hematology, Endocrinology, and
`
`Nephrology
`
`
`Center for Drug Evaluation and Research
`
`
`ENCLOSURES:
`
`
`• Content of Labeling
`
`
`o Prescribing Information
`
`
`o Medication Guides
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4583067
`
`
`
`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`PATRICK ARCHDEACON
`03/30/2020 12:55:09 PM
`
`Reference ID: 4583067
`
`(
`
`
`
`