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` NDA 203085/S-010
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`SUPPLEMENT APPROVAL
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`Bayer HealthCare Pharmaceuticals Inc.
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`Attention: James B. Davis
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`Deputy Director, Regulatory Affairs
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`100 Bayer Blvd.
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` P.O. Box 915
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` Whippany, NJ 07981
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` Dear Mr. Davis:
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` Please refer to your supplemental new drug application (sNDA) dated May 17, 2019,
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` received May 17, 2019, and your amendments, submitted under section 505(b)of the
` Federal Food, Drug, and Cosmetic Act (FDCA) for Stivarga (regorafenib) tablets, 40 mg.
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` This Changes Being Effected supplemental new drug application provides for revision to
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`the Adverse Reactions, Postmarketing Experience (6.2) subsection to include adverse
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` reactions of heart failure and nephrotic syndrome to the US prescribing information
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` (USPI).
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` APPROVAL & LABELING
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` We have completed our review of this application. It is approved, effective on the date of
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` this letter, for use as recommended in the enclosed agreed-upon labeling reflecting a
` “Revised” date of 06/2019 as indicated in the enclosed labeling.
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` WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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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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` 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
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`the FDA automated drug registration and listing system (eLIST), as described at
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` FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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` Prescribing Information), with the addition of any labeling changes in pending “Changes
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` Being Effected” (CBE) supplements, as well as annual reportable changes not included
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` in the enclosed labeling.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 4470739
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` NDA 203085/S-010
` Page 2
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` Information on submitting SPL files using eList may be found in the guidance for
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` industry SPL Standard for Content of Labeling Technical Qs and As.2
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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 include labeling
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` changes 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 Microsoft Word
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` 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
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` 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
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`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 (which includes new salts and new fixed combinations), new
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` 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
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`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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` Because none of these criteria apply to your application, you are exempt from this
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` requirement.
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 4470739
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` NDA 203085/S-010
` Page 3
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` PROMOTIONAL MATERIALS
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` You may request advisory comments on proposed introductory advertising and
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` 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
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` annotated references, and (3) the Prescribing Information to:
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`OPDP Regulatory Project Manager
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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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`Alternatively, you may submit a request for advisory comments electronically in eCTD
` format. For more information about submitting promotional materials in eCTD format,
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` see the draft guidance for industry Providing Regulatory Submissions in Electronic and
` Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs. 3
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` You must submit final promotional materials and Prescribing Information, accompanied
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` 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
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` Instructions for completing the form can be found at FDA.gov.5 For more information
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` about submission of promotional materials to the Office of Prescription Drug Promotion
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` (OPDP), see FDA.gov.6
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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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` 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.
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`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 4470739
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` NDA 203085/S-010
` Page 4
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`If you have any questions, call Kwadwo Korsah, Pharm.D., Regulatory Health Project
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` Manager, at (301) 796-6630.
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` Sincerely,
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` {See appended electronic signature page}
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` Jeffrey Summers, M.D.
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` Deputy Director for Safety
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` Division of Oncology Products 2
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` Office of Hematology and Oncology Products
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` Center for Drug Evaluation and Research
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` ENCLOSURE(S):
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`• Content of Labeling
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` U.S. Food and Drug Administration
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` Silver Spring, MD 20993
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` www.fda.gov
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`Reference ID: 4470739
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`Signature Page 1 of 1
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`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.
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`/s/
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`JEFFERY L SUMMERS
`07/31/2019 02:35:32 PM
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`Reference ID: 4470739
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