CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Apgroval Package for:
`
`APPLICA TI0NNUMBER:
`NDA 20-717/S-006
`
`Name:
`
`Provigil Tablets
`
`Generic Name:
`
`modafinil
`
`Sponsor:
`
`Cephalon, Inc.
`
`Approval Date:
`
`04/ 1 6/2003
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPLICA TI0N NUMBER:
`
`NDA 20-717/S—006
`
`CONTENTS
`
`7
`
`Reviews / Information Included in this Review —l
`
`
`
`Medical Review s
`
`
`
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`_"-—|-
` Adminlstratlve and Corres n ondence Document(s
`
`
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`, APPLICATIONNUMBER:
`NDA 20-717/S-006
`
`APPROVAL LETTER
`
`

`

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`
`Food and Drug Administration
`Rockville, MD 20857 ‘
`
`NDA 20-717/S-006
`
`Cephalon, Inc.
`Attention: Kenneth L. White, Pharm.D.
`Vice President, Regulatory Affairs
`145 Brandywine Parkway
`West Chester, PA 19380—4245
`
`Dear Dr. White:
`
`Please refer to your supplemental new drug application dated March 21,2003, received March 24,2003, submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act for Provigil (modafinil), 100 and 200 mg tablets.
`
`We acknowledge receipt of your submission dated March 21, 2003.
`
`Your submission of March 21, 2003 constituted a complete response to our February 21, 2003 action letter.
`
`This supplemental new drug application provides for revision of the blister unit and carton labeling.
`
`We completed our review of this application, as amended. This application is approved, efi‘ective on the date of this letter,
`for use as recommended in the agreed-upon labeling text.
`
`The final printed labeling (FPL) must be identical to the submitted labeling (immediate container and carton labels
`submitted March 21, 2003).
`
`Please submit the FPL electronically according to the guidance for industry titled Providing Regulatory Submissions in
`Electronic Format - NDA. Alternatively, you may submit 20 paper copies of the FPL as soon as it is available, in no case
`more than 30 days after it is printed. Please individually mount ten of the copies on heavy-weight paper or similar material.
`For administrative purposes, this submission should be designated "FPL for approved supplement NDA 20717/s—006.”
`Approval of this submission by FDA is not required before the labeling is used.
`
`If you issue a letter communicating important information about this drug product (Le, a “Dear Health Care Professional”
`letter), we request that you submit a copy of the letter to this NDA and a copy to the following address:
`
`MEDWATCH, HF-2
`FDA
`5600 Fishers Lane
`
`Rockville, MD 20857
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80 and 314.81).
`
`

`

`NDA 20-717/S-006
`
`Page 2
`
`If you have any questions, call Anna Homonnay, Regulatory Project Manager, at (301) 594-5535.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Maryla Guzewska, Ph.D.
`Chemistry Team Leader, Neurology Drugs for the
`Division ofNeuropharmacological Drug Products,
`(HFD-120)
`DNDC I, Office of New Drug Chemistry
`Center for Drug Evaluation and Research
`
`

`

`This'Is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Maryla Guzewska
`4/16/03 07:21:04 AM
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPLICATION NUMBER.-
`
`NDA 20-717/S—006
`
`APPROVABLE LETTER
`
`

`

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`(DEPARTMENTOFHEALTH&HUMANSERVICES
`
`PUb'icHealthService
`
`Food and Drug Administration
`Rockville, MD 20857
`
`‘ NDA 20—717/S—006
`
`Cephalon, Inc.
`Attention: Kenneth L. White, Pharm.D.
`Vice President, Regulatory Affairs
`145 Brandywine Parkway
`West Chester, PA 19380-4245
`
`Dear Dr. White:
`
`Please refer to your supplemental new drug application dated October 18, 2002, received October 21, 2002, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Provigil (modafinil), 100 and 200 mg tablets.
`
`We acknowledge receipt of your submission dated October 18, 2002.
`
`This supplemental new drug application provides for:
`
`1. An additional packaging configuration to be used for physician samples of Provigil Tablets
`2. A new site for blister packaging E,
`3
`
`We completed our review of this application, as amended, and it is approvable. Before this application may be approved,
`however, it will be necessary for you to address the following:
`
`1. A statement “Manufactured for Cephalon, Inc., West Chester, PA 19380” should be added to the labels for blister units,
`
`2. The strength of the drug (100 mg Tablets) should be made more prominent on both blister units and cartons,
`
`3. The size of the sign indicating the Controlled Drug should be enlarged.
`
`Within 10 days after the date of this letter, you are required to amend this application, notify us of your intent to file an
`amendment or follow one of your other options under 21 CFR 314.110. If you do not follow one of these options, we will
`consider your lack of response a request to withdraw the application under, 21 CFR 314.65. Any amendment should respond
`to all the deficiencies listed. We will not process a partial reply as a major amendment nor will the review clock be
`reactivated until all deficiencies have been addressed.
`
`If you have any questions, call Anna Homonnay, Regulatory Project Manager, at (301) 594-5535.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Maryla Guzewska, Ph.D.
`Chemistry Team Leader, Neurology Drugs for the
`Division of Neuropharmacological Drug Products,
`(HFD-120)
`DNDC 1, Office of New Drug Chemistry
`Center for Drug Evaluation and Research
`
`

`

`NDA 20-717/S-006
`
`Page 2
`
`Appears This Way
`On Original
`
`

`

`This is a representation of an electronic record’that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Maryla Guzewska
`2/21/03 01:50:25 PM
`
`

`

`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPLICA TION NUMBER:
`
`NDA 20-717/S-006
`
`CHEMISTRY REVIEW! S!
`
`

`

`CHEMIST'S REVIEW
`0|: SUPPLEMENT
`
`ORGANIZATION:
`NDANUMBER:
`SUPPLEMENT NUMBER:
`
`LETTER DATE
`
`STAMP DATE
`AMENDMENTS:
`
`LETTER DATES
`
`.
`,
`APPLICANT NAME AND ADDRESS:
`
`STAMP DATES
`
`.
`
`RECEIVEDBY CHEMIST:
`
`Cephalon, Inc.
`145 Brandywine Parkway
`West Chester, PA 19380-4245
`
`NAME OF DRUG:
`NONPROPRIETARY NAME:
`
`Provigil®
`Modafinil
`
`-
`
`CHEMICAL NAME] STRUCTURE: 2-'[(Diphenylmethyl)sulfinyl]acetamide
`
`‘ HFD-120
`20-717'
`SCP-006
`
`18—OCT-02
`
`21 -OCT-02
`
`‘N/A
`
`N/A
`
`12-DEC-02
`'
`
`
`
`DOSAGE FORM(s):
`POTENCY(IES):
`PHARMACOLOGICAL CATEGORY:
`SPECIAL PRODUCTS:
`How DISPENSED:
`RECORDS] REPORTS CURRENT:
`RELATEDIND/NDA/DMF(S):
`
`Tablets
`100 mg, 200 mg
`.
`Narcolepsy
`XX (NO)
`(YES)
`(OTC)
`XX (Rx)
`(NO)
`XX (YES)
`DMF #C Li DMF#['_ 3(amendment 92)
`
`SUPPLEMENT PROVIDES FOR: Additional packaging configuration for physician samples. In
`addition, a new site for blister packaging is added.
`
`COMMENTS: This is a PA supplement for a packaging change.'The sponsor describes
`the new blister sample package, which is a l:
`:1 film
`laminate and a push-through foil backing. Currently approved container closure system is
`C :l‘bottles with cap. Accelerated and real—time stability data are provided for similar
`blister packages, which are currently approved in Europe. The configuration and packaging
`materials for new blister packages are identical to European but the volume of the blister
`cavity is different: 8% larger cavity for 100 mg tablets and 25% smaller — for 200 mg tablets.
`Sponsor is relying on the stability profile of the drug product generated in bottles and
`. European blister packages, and is committing to place on stability first three batches Of the
`drug product in the new blister packs, and one batch per year thereafter. The additional
`packaging Site was inspected and received an Acceptable recommendation from the Office
`of Compliance (see EERIn CMC Review Notes). Two referenced DMFS for the packaging
`materials were reviewed and found to be adequate.
`Minor deficiencies have been found'In the labeling of the blister unit (see Review Notes).
`
`

`

`CONCLUSIONS AND RECOMMENDATIONS: Recommend Approvable.
`
`REVIEWER NAME
`
`SIGNATURE
`
`DATE COMPLETED '
`
`Lyudmila N. SoldatovaI Ph.D.
`
`cc: Orig: NDA 20-717
`‘
`HFD-120/Div. File
`HFD-120/AHomonnay/LSoldatova IMGuzewska
`Filename: 20717scp006.doc
`INlT: MGuzewska
`
`Februam 21I 2003
`
`

`

`Redacted 3
`
`page(s)
`
`_
`
`cftrade secretand/cr
`
`confidential commercial
`
`informaticn from
`
`
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Lyudmila Soldatova
`2/21/03 01:29;09 PM
`CHEMIST
`
`Maryla Guzewska
`2/21/03 01:48:41 PM
`CHEMIST
`
`

`

`CHEMIST'S REVIEW
`
`0F SUPPLEMENT
`
`ORGAN'ZAT'ON:
`NDA NUMBER:
`SUPPLEMENT NUMBER:
`
`LETTER DATE
`STAMP DATE
`AMENDMENTS:
`LETTER DATE
`STAMP DATE
`
`HFD-120
`20-717
`SCP-oos
`
`18-OCT -02 -
`21-OCT-02
`
`21-MAR-03
`24-MAR’-03
`
`RECEIVED BY CHEMIST:
`
`25-MAR-03
`
`APPLICANT NAME AND ADDRESS:
`
`NAME OF DRUG:
`NONPROPRIETARY NAME:
`
`Cephalon, Inc.
`145 Brandywine Parkway
`West Chester, PA 19380-4245 ’
`Provigil®
`Modafinil
`
`CHEMICAL NAME I STRUCTURE: 2-[(Diphenylmethyl)su|finyl]acetamide
`
`
`
`DOSAGE FORM(s):
`POTENCY(IES):
`PHARMACOLOGICAL CATEGORY:
`SPECIAL PRODUCTS:
`How DISPENSED:
`RECORDsI REPORTS CURRENT:
`RELATED IND l NDAI DMF(s):
`
`Tablets
`100 mg, 200 mg
`Narcolepsy
`XX (NO)
`(YES)
`(OTC)
`XX (Rx)
`(NO)
`XX (XES)
`IND 42,873, DMF #12 j] DMF # l:
`
`:l, DMF): j
`
`SUPPLEMENT PROVIDES FOR: Revised drafts of the blister unit and carton labeling for physician samples.
`
`COMMENTS: This is an amendment to the Prior Approval Supplement, 8-006, dated October 18, 2002 which
`provides for a packaging change. This amendment address the three requests made in the FDA’s Approvable
`Letter dated February 21, 2003. The sponsor provides a complete response to the minor deficiencies, found in
`the labeling of the blister units (100 mg and 200 mg tablets) and carton (200 mg).
`
`CONCLUSIONS AND RECOMMENDATIONS: Recommend Approval.
`
`REVIEWER NAME
`
`SIGNATURE
`
`-
`
`DATE- COMPLETED
`
`Lyudmila N. Soldatova, Ph.D.
`
`cc: Orig: NDA 20-717
`HFD-120/Div. File
`
`HFD-120/AHomonnay/LSoldatova IMGuzewska
`Filename: 20717scp006Amend1 .doc
`INlT: MGuzewska
`
`April 15I 2003
`
`

`

`Redacted
`
`0'2
`
`page(s)
`
`A
`
`oftrade secret and/or
`
`confidential commercial
`
`information from
`
`,
`.
`£5
`QBV
`_
`.Oi/leyvu‘
`
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature. -
`
`Lyudmila Soldatova
`4/15/03 02:57:37 PM
`CHEMIST
`
`Maryla Guzewska
`4/16/03 07:19:37 AM
`CHEMIST
`
`

`

`ENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPLICATION NUMBER:
`
`NDA 20-717/S-0‘06
`
`ADMINISTRATIVE and
`
`CORRESPONDENCE DOCUMENTS
`
`

`

`Redacted
`
`1
`
`- lpage(s) ,
`
`.
`
`of trade secret and/or
`
`confidential commercial
`
`information from
`
`
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Lyudmila Soldatova
`2/20/03 04:37:38 PM
`CHEMIST
`
`Maryla Guzewska
`2/21/03 01:25:38 PM
`CHEMIST
`
`

`

`i .4 DEPARTMENTOF HEALTH&HUMANSERVICES
`
`
`
`PUbliC Health Service
`
`NDA 20—7 17
`
`'
`
`PRIOR APPROVAL SUPPLEMENT
`
`Food and Drug Administration
`Rockville. MD 20857
`
`Cephalon, Inc.
`Attention: Paul M. Kirsch
`
`Senior Director, Regulatory Affairs
`145 Brandywine Parkway
`West Chester, PA 193 80-4245
`
`Dear Mr. Kirsch
`
`We have received your supplemental drug application submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act for the following:
`
`Name of Drug Product:
`
`PROVIGIL (modafinil) Tablets
`
`NDA Number: '
`
`20-717
`
`Supplement number:
`Date of supplement:
`
`S-006
`October. 18, 2002
`
`Date of receipt:
`
`October 21, 2002
`
`Unless we notify you within 60 days of the receipt date that the application is not sufficiently complete to
`pennit a substantive review, this application will be filed under section 505(b) of the Act on December
`21, 2002 in accordance with 21 CFR 314.101(a).
`
`All communications concerning this supplement should be addressed as follows:
`
`US. Postal Service:
`
`Center for Drug Evaluation and Research
`Division of Neuropharmacological Drug Products, HFD-120
`Attention: Division Document Room, 4008
`5600 Fishers Lane
`
`Rockville, Maryland 20857
`
`

`

`NDA 20-717
`
`Page 2
`
`Courier/Overnight Mail:
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Neurophannacological Drug products, HFD-120
`Attention: Division Document Room, 4008
`1451 Rockville Pike
`
`Rockville, Maryland 20852
`
`If you have any questions, call Anna Marie Homonnay, R.Ph., Regulatory Health Project Manager, at
`(301) 594-2850.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Maryla Guzewska, Ph.D.
`Chemistry Team Leader, Neurology Drugs for the
`Division of Neuropharmacological Drug Products
`(I-lFD-l20) '
`DNDC I, Office of New Drug Chemistry
`Center for Drug Evaluation and Research
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Maryla Guzewska
`10/23/02 09:13:09 AM
`
`