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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 020717/S-030, S-034, and S-036
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`Cephalon Inc.
`Attention: Paul Kirsch
`Senior Director and Group Leader, Regulatory Affairs
`41 Moores Box 4011
`Frazer, PA 19355
`
`Dear Mr. Kirsch:
`
`Please refer to your Supplemental New Drug Applications (sNDAs), submitted under section
`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Provigil (modafinil) Tablets
`100 and 200 mg for the following:
`
`
`Application
`
`
`Submitted on
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`Received on
`
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`NDA 020717/S-030 April 11, 2008
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`April 14, 2008
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`Supplement
`type
`Changes
`Being
`Effected
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`NDA 020717/S-034 January 23, 2009 January 26, 2009
`
`Prior
`Approval
`
`Supplement provides
`for:
`Adds “aggression” to
`
` WARNINGS:
` Psychiatric Symptoms
`
`subsection of the label
`
`Risk Evaluation and
`Mitigation Strategy
`(REMS), Medication
`Guide and pregnancy
`registry
`Describes ADHD
`studies in Pediatric
`Section
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` NDA 020717/S-036
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`July 29, 2009
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`July 30, 2009
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`Changes
`Being
`Effected
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`We acknowledge receipt of your submissions dated: March 3, 2009, October 26, 2009,
`January 6, 2010, March 5, 2010, April 12, and October 4 and 5, 2010.
`
`We have completed our review of these applications, as amended, and they are approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
`
`
`As soon as possible, but no later than 14 days from the date of this letter, submit, using the FDA
`automated drug registration and listing system (eLIST), the content of labeling [21 CFR
`314.50(l)] in structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
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` NDA 020717/S-030, S-034, and S-036
`Page 2
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`identical to the enclosed labeling (text for the package insert and Medication Guide) and include
`the labeling changes proposed in any pending “Changes Being Effected” (CBE) supplements.
`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`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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`Within 14 days from the date of this letter, please amend all pending supplemental applications
`for these NDAs, including pending "Changes Being Effected" (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
`structured product labeling (SPL) format that includes the changes approved in this supplemental
`application.
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`We request that the revised labeling approved today be available on your website within 10 days
`of receipt of this letter.
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`CARTON AND IMMEDIATE CONTAINER LABELS
`
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`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels as soon as they are available, but no more than 30 days after they are
`printed. Please submit these labels electronically according to the guidance for industry titled
`“Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product
`Applications and Related Submissions Using the eCTD Specifications (October 2005)”.
`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
`heavy-weight paper or similar material. For administrative purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 020717/S-034.” Approval
`of this submission by FDA is not required before the labeling is used.
`
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`Section 505-1 of the FDCA authorizes FDA to require the submission of a risk evaluation and
`mitigation strategy (REMS) if FDA becomes aware of new safety information and makes a
`determination that such a strategy is necessary to ensure that the benefits of the drug outweigh
`the risks (section 505-1(a)). The details of the REMS requirements were outlined in our REMS
`notification letter dated September 26, 2008.
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`Since Provigil (modafinil) was approved on December 24, 1998, we have become aware of
`controlled clinical studies and postmarketing reports that provide evidence of serious skin and
`other hypersensitivity reactions, especially with pediatric use. This information was not
`available when Provigil (modafinil) was granted marketing authority. We consider this
`information to be “new safety information” as defined in section 505-1(b) of FDCA.
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` NDA 020717/S-030, S-034, and S-036
`Page 3
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`Your proposed REMS, submitted on October 5, 2010 and appended to this letter, is approved.
`The REMS consists of a Medication Guide, a communication plan, and a timetable for
`submission of assessments of the REMS.
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`The REMS assessment plan should include but is not limited to the following:
`
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`a. An evaluation of patients’ understanding of the serious risks of Provigil
`b. A report on periodic assessments of the distribution and dispensing of the Medication
`Guide in accordance with 21 CFR 208.24
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`c. A report on failures to adhere to distribution and dispensing requirements, and corrective
`actions taken to address noncompliance
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`d. Information about the communication plan in cluding the sources of recipient lists, the
`number of recipients on each mailing list, the date(s) of the mailing, and the documents
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`including in each mailing.
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`Assessments of an approved REMS must also include, under section 505-1(g)(3)(B) and (C),
`information on the status of any postapproval study or clinical trial required under section 505(o)
`or otherwise undertaken to investigate a safety issue. With respect to any such postapproval
`study, you must include the status of such study, including whether any difficulties completing
`the study have been encountered. With respect to any such postapproval clinical trial, you must
`include the status of such clinical trial, including whether enrollment has begun, the number of
`participants enrolled, the expected completion date, whether any difficulties completing the
`clinical trial have been encountered, and registration information with respect to requirements
`under subsections (i) and (j) of section 402 of the Public Health Service Act. You can satisfy
`
`these requirements in your REMS assessments by referring to relevant information included in
`the most recent annual report required under section 506B and 21 CFR 314.81(b)(2)vii and
`including any updates to the status information since the annual report was prepared. Failure to
`comply with the REMS assessments provisions in section 505-1(g) could result in enforcement
`action.
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`We remind you that in addition to the assessments submitted according to the timetable included
`in the approved REMS, you must submit a REMS assessment and may propose a modification to
`the approved REMS when you submit a supplemental application for a new indication for use as
`described in section 505-1(g)(2)(A) of FDCA.
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`Prominently identify the submission containing the REMS assessments or proposed
`modifications with the following wording in bold capital letters at the top of the first page of the
`submission:
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`NDA 020717 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 020717
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
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`NEW SUPPLEMENT (NEW INDICATION FOR USE)
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`FOR NDA 020717
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` NDA 020717/S-030, S-034, and S-036
`Page 4
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`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert(s)
`to:
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert(s), at the time of initial dissemination or publication, accompanied by a Form
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`FDA 2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For
`more information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials for your drug product that include representations about your drug
`product must be promptly revised to make it consistent with the labeling changes approved in
`this supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions to
`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 or by
`fax to 301-847-8444.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and to the following address:
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`
`
`MedWatch
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`Food and Drug Administration
`
`5600 Fishers Lane, Room 12B05
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`Rockville, MD 20857
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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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` NDA 020717/S-030, S-034, and S-036
`Page 5
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`If you have any questions, call Beverly Conner at (301) 796-1171.
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`Sincerely,
`
` {See appended electronic signature page}
`
`Russell Katz, M.D.
`Director
`
`Division of Neurology Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`
`Enclosures:
`Content of Labeling
`Carton and Container Labeling
`REMS
`REMS Materials
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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/
`----------------------------------------------------
`
`RUSSELL G KATZ
`10/21/2010
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`Reference ID: 2851947
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