Food and Drug Administration
`Silver Spring MD 20993
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` NDA APPROVAL
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022255, 022253/S-006, 022254/S-003
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`Schwarz Biosciences, Inc.
`Attention: Susan Tegtmeyer, M. S.
`Senior Manager Regulatory Affairs
`1950 Lake Park Drive
`Smyrna, GA 30080
`
`Dear Ms. Tegtmeyer:
`
`
`
`
`Please refer to your September 28, 2007, New Drug Application (NDA) 022255, received
`September 28, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
`Act for Vimpat (lacosamide) Oral Solution, 10 mg/ml.
`
`
`
`We acknowledge receipt of your submissions to NDA 022255 dated October 16, 2009, and
`February 4, March 31, and April 20, 2010.
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`The October 16, 2009, submission constituted a complete response to our October 28, 2008,
`action letter.
`
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`This new drug application provides for the use of Vimpat (lacosamide) Oral Solution as
`adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged 17
`years and older.
`
`We further refer to your August 21, 2009, supplemental NDAs 022253/S-006 and 022254/S-003,
`received August 24, 2009, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act for Vimpat (lacosamide) Tablets and Injection. These supplements provide for a
`comprehensive Medication Guide and modified risk evaluation and mitigation strategy (REMS).
`
`We acknowledge receipt of your submissions to NDAs 022253/S-006 and 022254/S-003 dated
`October 5 and 6, 2009, and March 31, and April 13, 2010. Finally, we acknowledge receipt of
`your April 20, 2010 amendments to NDAs 022253/S-006 and 022254/S-003 containing a
`modified REMS and REMS assessment.
`
`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.
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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`Page 00001
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`ARGENTUM Exhibit 1183
`Argentum Pharmaceuticals LLC v. Research Corporation Technologies, inc.
`IPR2016-00204
`
`

`
`NDA 022255, 022253/S-006, 022254/S-003
`Page 2
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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, please submit 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
`identical to the enclosed labeling (text for the package insert and Medication Guide). For
`administrative purposes, please designate this submission, “SPL for approved NDAs 022255,
`022253/S-006, and 022254/S-003.”
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`
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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 carton and immediate
`container labels submitted on April 15, 2010, 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
`022255.” Approval of this submission by FDA is not required before the labeling is used.
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`
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
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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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`We are waiving the pediatric study requirement for ages 0 to 1 month for these applications
`because necessary studies are impossible or highly impracticable because there are too few
`children with partial onset seizures in this age group to study.
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`In addition, we are deferring submission of your pediatric studies in partial onset seizures for
`ages 1 month up to 17 years for this application because this product is ready for approval for use
`in adults and the pediatric studies have not been completed.
`
`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) are required postmarketing studies. The status of these postmarketing
`studies must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the
`FDCA. This required study is listed below.
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`Page 00002
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`NDA 022255, 022253/S-006, 022254/S-003
`Page 3
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`1636-1 Deferred pediatric studies under PREA for the adjunctive treatment of partial
`onset seizures in pediatric patients ages 1 month up to 17 years.
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`Final Report Submission: July 2013
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`
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`this required pediatric postmarketing study must be clearly designated “Required Pediatric
`Assessment”.
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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 REMS if FDA
`determines 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 for Vimpat (lacosamide) Oral
`Solution were outlined in our REMS notification letter dated January 11, 2010.
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`The REMS for Vimpat (lacosamide) Tablets and Injection was originally approved on
`October 28, 2008. The REMS consists of a Medication Guide and a timetable for submission of
`assessments of the REMS. In a letter dated March 19, 2010 we notified you that the approved
`REMS for Vimpat (lacosamide) Tablets and Injection must be modified to include Vimpat
`(lacosamide) Oral Solution. The proposed modifications to the REMS consist of the addition of
`the oral solution formulation and revisions to the Medication Guide to include more
`comprehensive safety information.
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`Your proposed modified REMS, submitted on April 20, 2010 and appended to this letter, is
`approved. The REMS consists of a Medication Guide and a timetable for submission of
`assessments of the REMS.
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`
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`The timetable for submission of assessments of the REMS will remain the same as that approved
`on October 28, 2008.
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`The REMS assessment plan should include but is not limited to the following:
`a. An evaluation of patients’ understanding of the serious risks of Vimpat (lacosamide)
`Tablets, Injection, and Oral Solution
`b. A report on periodic assessments of the distribution and dispensing of the Medication
`Guide in accordance with 21 CFR 208.24
`c. A report on failures to adhere to distribution and dispensing requirements, and
`corrective actions taken to address noncompliance
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`
`
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`The requirements for assessments of an approved REMS under section 505-1(g)(3) include, in
`section 505-1(g)(3)(B) and (C), requirements for information on the status of any postapproval
`study or clinical trial required under section 505(o) or otherwise undertaken to investigate a
`safety issue. 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
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`Page 00003
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`NDA 022255, 022253/S-006, 022254/S-003
`Page 4
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`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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`
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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 future submissions containing the REMS assessment or proposed REMS
`modification with the following appropriate wording in bold capital letters at the top of the first
`page of the submission:
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`NDA 022253, 022254, & 022255 REMS ASSESSMENT
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`NEW SUPPLEMENT FOR NDA 022253, 022254, & 022255
`PROPOSED REMS MODIFICATION
`REMS ASSESSMENT
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`NEW SUPPLEMENT FOR (NEW INDICATION FOR USE) FOR NDA022253,
`022254, & 022255
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`REMS ASSESSMENT
`PROPOSED REMS MODIFICATION (if included)
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`
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`If you do not submit electronically, please send 5 copies of REMS-related submissions.
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`ADDITIONAL CMC COMMENTS
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`1. Based on our analysis of the stability data and in accordance with ICH Q1E, we grant the
`proposed 18 month expiry for Vimpat® 10 mg/mL Oral Solution packaged in
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`200 mL,
` round amber PET bottles and in 200 mL
`round amber
`glass bottles, stored at controlled room temperature [25ºC (77ºF); excursions 15-30ºC
`(59-86ºF)].
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`2. Based on our analysis of the in-use stability data, we grant an in-use expiry of seven (7)
`weeks after first opening of the bottle for Vimpat® (lacosamide) Oral Solution.
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`3. Based on our review, we grant the request for a biowaiver for the in vivo bioequivalence
`study for Vimpat® (lacosamide) Oral Solution 10 mg/mL.
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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
`to:
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`
`(b) (4)
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`(b) (4)
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`(b) (4)
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`Page 00004
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`NDA 022255, 022253/S-006, 022254/S-003
`Page 5
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`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, at the time of initial dissemination or publication, accompanied by a Form 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
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`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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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
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`the letter to both this NDA and to the following address:
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`
`MedWatch
`
`Food and Drug Administration
`
`Suite 12B-05
`
`5600 Fishers Lane
`
`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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`If you have any questions, call Susan Daugherty, Regulatory Project Manager, at (301) 796-0878.
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`
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`Sincerely,
`
` {See appended electronic signature page}
`
`Russell Katz, M.D.
`Director
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`Division of Neurology Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`
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`Enclosure: Label and REMS
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`Page 00005
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`Application
`Type/Number
`--------------------
`NDA-22255
`
`Submission
`Type/Number
`--------------------
`ORIG-1
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`NDA-22253
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`SUPPL-6
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`NDA-22254
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`SUPPL-3
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`Submitter Name
`
`Product Name
`
`--------------------
`SCHWARZ
`BIOSCIENCES INC
`SCHWARZ
`BIOSCIENCES INC
`SCHWARZ
`BIOSCIENCES INC
`
`------------------------------------------
`VIMPAT
`
`VIMPAT
`
`VIMPAT
`
`---------------------------------------------------------------------------------------------------------
`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
`04/20/2010
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`Page 00006