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` DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` Food and Drug Administration
` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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` NDA 204063/S-014
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` Biogen Idec
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` Attention: Nadine D. Cohen, Ph.D.
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` Senior Vice President, Regulatory Affairs
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` 14 Cambridge Center
` Cambridge, MA 02142
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`Dear Dr. Cohen:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received August 5,
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`2015, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
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`Cosmetic Act (FDCA) for Tecfidera (dimethyl fumarate).
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`This “Prior Approval” supplemental new drug application provides for revisions to the following
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`sections of the prescribing information:
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` Section 5.2 Progressive Multifocal Leukoencephalopathy
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` Section 5.3 Lymphopenia
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert, text for the
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`patient 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
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`labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
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`“SPL Standard for Content of Labeling Technical Qs and As” at
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`Reference ID: 3894593
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` NDA 204063/S-014
` Page 2
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`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
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
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`electronically in eCTD format. For more information about submitting promotional materials in
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`eCTD format, see the draft Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
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`CM443702.pdf ).
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`REQUESTED PHARMACOVIGILANCE
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`We request that you perform postmarketing surveillance and enhanced pharmacovigilance for
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`pancreatitis. All confirmed or possible cases of pancreatitis must be reported to the Division in
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`an expedited fashion. For reported cases with incomplete information, we ask that you attempt
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`to collect additional information including, but not limited to, the following: time between
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`initiation of Tecfidera and pancreatitis symptoms onset, concomitant medications, concomitant
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`medical conditions predisposing to pancreatitis, pertinent lab and imaging data, rechallenge
`results, and outcome information. We also request that in your periodic safety update reports you
`provide synthesized analyses of all cases of pancreatitis along with incidences from clinical trials
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`and reporting rates calculated from postmarketing data.
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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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`Reference ID: 3894593
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` NDA 204063/S-014
` Page 3
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` If you have any questions, contact Laurie Kelley, PA-C, Regulatory Project Manager, at
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` 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.
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`Deputy Director for Safety
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`Division of Neurology Products
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`Office of Drug Evaluation I
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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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`Reference ID: 3894593
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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
`02/29/2016
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`Reference ID: 3894593
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