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` NDA 204063/S-25
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`SUPPLEMENT APPROVAL
`
`
`
`
`
`
` Biogen, Inc.
`
` Attention: Trevor Mill
`
` Senior Vice President,
`
` Global Safety and Regulatory Sciences
`
`
` 225 Binney Street
` Cambridge, MA 02142
`
`
`
`
`
`Dear Mr. Mill:
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`
`
`Please refer to your supplemental new drug application (sNDA) dated and received
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`
`
`
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`June 12, 2019, and your amendments, submitted under section 505(b) of the Federal
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`Food, Drug, and Cosmetic Act (FDCA) for Tecfidera (dimethyl fumarate) 120 mg and
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`240 mg capsules.
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`
`
`
`
`
`This Prior Approval supplemental new drug application provides for revisions to the
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`
`
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`Warnings and Precautions section (5), including the addition of a new subsection (5.3)
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`
`
`
`
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`describing the risk for serious herpes zoster infections and other serious opportunistic
`
`
`infections. Corresponding revisions were also made to Section 6 (Adverse Reactions),
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`
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`Section 17 (Patient Counseling Information), and the Patient Package Insert. In
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`addition, revisions were made to Section 5.2 (Warnings and Precautions; Progressive
`
`Multifocal Leukoencephalopathy) pertaining to the degree and duration of lymphopenia
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`
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`reported in postmarketing cases of progressive multifocal leukoencephalopathy to
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`
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`reflect that PML has occurred in the absence of prolonged moderate to severe
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`lymphopenia.
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`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
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`
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`on the date of this letter, for use as recommended in the enclosed agreed-upon
`
`labeling.
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`
`
`
`Reference ID: 4532306
`
`

`

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` NDA 204063/S-25
` Page 2
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`
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` CONTENT OF LABELING
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`
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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 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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`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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`
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`The SPL will be accessible from publicly available labeling repositories.
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`
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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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`
`
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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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`
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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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`
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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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`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
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`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
`
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`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.
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`
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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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`
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`
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 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: 4532306
`
`

`

`
`
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` NDA 204063/S-25
` 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
`
`
`
`
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`Alternatively, you may submit a request for advisory comments electronically in eCTD
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`
`
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`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
`
`Prescription Drugs.3
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`
`
`
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`You must submit final promotional materials and Prescribing Information, accompanied
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`
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`by a Form FDA 2253, at the time of initial dissemination or publication
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`
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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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`
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`
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`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
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`
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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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`
`
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`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
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`
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`in your promotional materials should include prominent disclosure of the important new
`
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`safety information that appears in the revised labeling. Within 7 days of receipt of this
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`
`
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`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4) to the
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`
`
`
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`address above, by fax to 301-847-8444, or electronically in eCTD format. For more
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`
`
`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 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
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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
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`
`
`Reference ID: 4532306
`
`

`

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` NDA 204063/S-25
` Page 4
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` 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, please call Sandra Folkendt, Regulatory Project Manager, at
`
`(240) 402-2804.
`
`
`
`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
`
`
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`ENCLOSURE(S):
`
`
`• Content of Labeling
`
`
`o Prescribing Information
`
`
`o Patient Package Insert
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`
`
`Reference ID: 4532306
`
`

`

`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
`12/11/2019 05:29:14 PM
`
`Reference ID: 4532306
`
`

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