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`
`U.S. FOOD & DRUG
`
`ADMINISTRATION
`
`
`
` NDA 204063 / S-28 & 30
`
`
`
`SUPPLEMENT APPROVAL
`
`
`Biogen Inc.
`Attention: Priya Singhal, MD, MPH
`Senior Vice President
`Global Safety and Regulatory Sciences
`
`225 Binney Street
`Cambridge, MA 02142
`
`
`Dear Dr. Singhal:
`
`
`Please refer to your supplemental new drug applications (sNDAs) dated and received
`April 18, 2022, and August 17, 2022, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for Tecfidera (dimethyl fumarate) delayed-
`release capsules.
`
`
`Prior Approval sNDA 204063/S-28 provides for an update to the exposure information in
`Section 6.1 (Adverse Reactions; Clinical Trials Experience).
`
`We also refer to our letter dated July 19, 2022, notifying you, under Section 505(o)(4) of
`the FDCA, of new safety information that we have determined should be included in the
`labeling for Tecfidera. This information pertains to the risk of acute pancreatitis.
`
`
`Supplemental new drug application 204063/S-30 provides for revisions to the labeling
`for Tecfidera, consistent with our July 19, 2022, Safety Labeling Change Notification
`letter.
`
`Additionally, we request that pancreatitis be added as an Adverse Event of Special
`Interest for any future studies involving Tecfidera.
`
`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.
`
`
`Reference ID: 5053326
`
`

`

`NDA 204063/S-28 & 30
`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 Patient Information), 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 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
`format, that includes the changes approved in these supplemental applications, 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).
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final 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
`
`PATENT LISTING REQUIREMENTS
`
`
` 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.
`
` 3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`
`Reference ID: 5053326
`
`

`

`NDA 204063/S-28 & 30
`Page 3
`
`
`
`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
`submitted in a supplement require you to submit patent information for listing in the
`Orange Book upon approval of the supplement. You must submit the patent information
`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
`supplement for the patent information to be timely filed (see 21 CFR
`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
`require the submission of a request to remove patent information from the Orange Book
`are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, contact CDR Candido Alicea, Regulatory Project Manager, at
`(240) 402-8310.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`Alice Hughes, MD
`
`Deputy Director for Safety
`Division of Neurology 2
`Office of Neuroscience
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE:
`(cid:120) Content of Labeling
`o Prescribing Information
`
`o Patient Information
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 5053326
`
`

`

`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/
`------------------------------------------------------------
`
`ALICE HUGHES
`09/29/2022 01:38:30 PM
`
`Reference ID: 5053326
`
`