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` NDA 204063/S-032
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` SUPPLEMENT APPROVAL
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`Biogen, Inc.
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`Attention: Priya Singhal, MD, MPH
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`Senior Vice President, Global Safety and Regulatory Sciences
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`225 Binney Street
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`Cambridge, MA 02142
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`Dear Dr. Singhal:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`October 27, 2023, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Tecfidera (dimethyl fumarate)
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`capsules.
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`We also refer to our letter dated September 29, 2023, notifying you, under Section
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`505(o)(4) of the FDCA, of new safety information that we have determined should be
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`included in the labeling for fumaric acid esters. This information pertains to the risk of
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`severe gastrointestinal (GI) adverse events.
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`This supplemental new drug application provides for revisions to the labeling for
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`Tecfidera, consistent with our September 29, 2023, letter.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved, effective
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`on the date of this letter, for use as recommended in the enclosed agreed-upon
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`labeling.
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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
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`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 and Patient Package Insert), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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`reportable changes not included in the enclosed labeling.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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`Reference ID: 5292845
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` NDA 204063/S-032
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` 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
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`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
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`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
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`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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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and
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`promotional labeling. For information about submitting promotional materials, see the
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`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
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`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
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`[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
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`All promotional materials that include representations about your drug product must be
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`promptly revised to be consistent with the labeling changes approved in this
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`supplement, including any new safety-related information [21 CFR 314.70(a)(4)]. The
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`revisions in your promotional materials should include prominent disclosure of the
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`important new safety-related information that appears in the revised labeling. Within 7
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`days of receipt of this letter, submit your statement of intent to comply with
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`21 CFR 314.70(a)(4).
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`PATENT LISTING REQUIREMENTS
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`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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`submitted in a supplement require you to submit patent information for listing in the
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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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` 3 For the most recent version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/media/128163/download.
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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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`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: 5292845
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` NDA 204063/S-032
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` Page 3
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`Orange Book upon approval of the supplement. You must submit the patent information
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`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
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`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
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`supplement for the patent information to be timely filed (see 21 CFR 314.53(c)(2)(ii)).
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`You also must ensure that any changes to your approved NDA that require the
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`submission of a request to remove patent information from the Orange Book are
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`submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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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`If you have any questions, contact Elaine Gettelman by phone at (240) 402-6425 or by
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`email at elaine.gettelman@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature page}
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`Alice T.D. Hughes, MD
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`Deputy Director for Safety
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`Division of Neurology 2
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`Office of Neuroscience
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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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`o Prescribing Information
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`o Patient Package Insert
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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: 5292845
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`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/
`------------------------------------------------------------
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`ALICE HUGHES
`12/13/2023 02:10:18 PM
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`Reference ID: 5292845
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