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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 204063/S-020
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`SUPPLEMENT APPROVAL
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`Food and Drug Administration
`Silver Spring MD 20993
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`Biogen
`Attention: Trevor Mill
`Senior Vice President, Regulatory Affairs
`225 Binney Street
`Cambridge, MA 02142
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`Dear Mr. Mill:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received June 30,
`2017, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Tecfidera (dimethyl fumarate) 120 mg and 240 mg delayed-release
`capsules.
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`This Prior Approval supplemental new drug application provides for revisions to Section 5.2
`(Warnings and Precautions; Progressive Multifocal Leukoencephalopathy). These revisions
`indicate that lower PML-related mortality and morbidity have been reported following
`discontinuation of another MS medication associated with PML in patients with PML who were
`initially asymptomatic compared to patients with PML who had characteristic clinical signs and
`symptoms at diagnosis, and state that monitoring with MRI for signs that may be consistent with
`PML may be useful, and that any suspicious findings should lead to further investigation to allow
`for an early diagnosis of PML, if present. The application also provides for revisions to Section
`8 (Use in Specific Populations; Pregnancy [8.1] and Lactation [8.2]), to comply with the
`Pregnancy and Lactation Labeling Rule (PLLR).
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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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 the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and patient
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`Reference ID: 4195850
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`

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`NDA 204063/S020
`Page 2
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`package insert) 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.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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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 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 MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, 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).
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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, 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(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`PROMOTIONAL MATERIALS
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`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 package insert(s) to:
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`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 format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
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`Reference ID: 4195850
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`

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`NDA 204063/S020
`Page 3
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`You must submit final promotional materials and package insert(s), 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
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
`electronically in eCTD format. For more information about submitting promotional materials in
`eCTD format, see the draft guidance for industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, contact Laurie Kelley, Regulatory Project Manager, at
`laurie.kelley@fda.hhs.gov.
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`Sincerely,
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`{See appended electronic signature page}
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` Alice Hughes, M.D.
` Deputy Director for Safety
` Division of Neurology Products
` Office of Drug Evaluation I
` Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`Reference ID: 4195850
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`

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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`ALICE HUGHES
`12/15/2017
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`Reference ID: 4195850
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