~... .. ~ ~
`( ~DEPARTMENT OF HEALTH AND HUMAN SERVICES
`<~~~t._
`~...(J
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`NDA 204063/S-003 , S-008, and S-010
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`SUPPLEMENT APPROVAL
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`Biogen Idee
`Attention: Nadine D. Cohen, Ph.D.
`Senior Vice President, Regulat01y Affairs
`14 Cambridge Center
`Cambridge, MA 02142
`
`Dear Dr. Cohen :
`
`
`Please refer to your Supplemental New Dmg Applications (sNDA):
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`
`NDA 204063/S-003
`
`T ecfidera (dimethyl fumarate)
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`Januruy 31 , 2014 Febmru·y 3, 2014
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`Product Name
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`Submitted on:
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`Received on:
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`submitted as a "Prior
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`Highlights and Section 4: Contm indication for patients with known hypersensi
`dimethyl fumarate or to any of the excipients of Tecfidera
`Section 5.1: Hypersensitivity reactions (section added)
`Section 8.1:
`·
`number
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`and website added
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`tivity to
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`July 28, 2014
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`Highlights: Wrunings and Precautions
`Section 2.1 -Dosing and Adminisu·ation
`Section 5.2 - Progressive Multifocal Leukoencephalopathy (section added)
`Section 5.3 - Lymphopenia
`Section 17 - Patient Cmmseling Infonnation
`Patient Inf01mation
`
`Reference ID : 3666921
`
`

`

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` NDA 204063/S-003, 008, and 010
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` Page 2
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` We also acknowledge receipt of your amendments to NDA 204063/S-003 dated February 21,
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`2014 and November 19, 2014; NDA 204063/S-008 dated August 25, 2014, October 17, 2014,
`October 23, 2014, and October 29, 2014; and NDA 204063/S-010 dated November 7, 2014,
`November 25, 2014, November 26, 2014, and December 3, 2014.
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`
` APPROVAL & LABELING
`
` We have completed our review of these supplemental applications, as amended. They are
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`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
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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
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`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
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`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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`
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`“SPL Standard for Content of Labeling Technical Qs and As at
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`
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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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`
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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 these supplemental applications, 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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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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`(3) the package insert(s) to:
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`
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`
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`Reference ID: 3666921
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`

`

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` NDA 204063/S-003, 008, and 010
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` Page 3
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`
` Food and Drug Administration
`
` Center for Drug Evaluation and Research
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` Office of Prescription Drug Promotion (OPDP)
`
`
` 5901-B Ammendale Road
` Beltsville, MD 20705-1266
`
`
`
`
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`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
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` 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.
`
`
`
` All promotional materials that include representations about your drug product must be promptly
` revised to be consistent with the labeling changes approved in these supplements, including any
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`
`
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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 or by fax to 301-847-8444.
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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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`
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`(21 CFR 314.80 and 314.81).
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`
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`If you have any questions, contact Laurie Kelley, PA-C, Regulatory Project Manager, via
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`
`
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`telephone at (301) 796-5068 or via email at Laurie.Kelley@fda.hhs.gov.
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`Sincerely,
`
`
`{See appended electronic signature page}
`
`
`Billy Dunn, M.D.
`
`Acting Director
`
`Division of Neurology Products
`
`Office of Drug Evaluation I
`
`Center for Drug Evaluation and Research
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`
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3666921
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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/
`----------------------------------------------------
`
`WILLIAM H Dunn
`12/03/2014
`
`Reference ID: 3666921
`
`