CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
` 002255Orig1s000
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`OTHER ACTION LETTER(s)
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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 22-255
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`COMPLETE RESPONSE
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`Schwarz Biosciences, Inc.
`Attention: Alan Blumberg
`Senior Director, US Regulatory Affairs
`P.O. Box 110167
`Research Triangle Park, NC 27709
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`Dear Mr. Blumberg:
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`Please refer to your new drug application (NDA) dated September 28, 2007, received September
`28, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, for
`Vimpat (lacosamide) Oral Solution
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`We acknowledge receipt of your additional submissions dated:
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`November 26, 2007 March 20, 2008 April 30, 2008
`December 13, 2007 April 3, 2008
`May 9, 2008
`January 23, 2008
`April 9, 2008
`May 27, 2008
`February 13, 2008
`April 14, 2008
`June 11, 2008
`February 22, 2008
`April 18, 2008
`July 11, 2008 (2)
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`We have completed the review of your application, as amended, and have determined that we
`cannot approve this application in its present form. Before this application may be approved, we
`ask that you address the following issues.
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`CLINICAL
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`As discussed with you during a teleconference with the Agency on April 23, 2008, we have
`concluded that the solution concentration
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`lead to significant dosing errors. Specifically, we are concerned that the recommended or
`prescribed doses (in milligrams) can not be measured accurately with this concentration
` of solution. The Agency’s Division of Medication Error and Prevention Analysis
`(DMEPA) notes that most liquids are prescribed and measured in milliliters, and that
`postmarketing experience has shown that demarcation in milligrams instead of milliliters is
`associated with numerous medication errors.
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`July 17, 2008
`July 30, 2008
`August 1, 2008
`August 14, 2008
`August 27, 2008
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`September 4, 2008
`September 23, 2008
`October 15, 2008
`October 21, 2008
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`(b) (4)
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`(b)
`(4)
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`(b) (4)
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`NDA 22-255
`Page 2
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`In addition,
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`concerns regarding the accuracy of the measured dose if, for example, a small dose is prescribed
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`We note your recognition of these issues in an email from Ms. Misty D’Ottavio of your firm sent
`to Dr. Ware of this Agency on April 28, 2008 as follow-up to the teleconference with you on April
`23, 2008. In that email Ms. D’Ottavio states the following:
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`“Schwarz will evaluate other concentrations of lacosamide oral syrup [sic] to alleviate the
`Agency’s concern with prescribing and dosing errors and to eliminate the need for a
`special dosing device. A previous formulation of lacosamide oral syrup [sic] utilized a
`10 mg/mL concentration, and therefore, Schwarz may first look at that concentration with
`some minor optimization to expedite development efforts. The revised
`formulation/concentration, along with all appropriate data, will be provided to the
`Agency as soon as available.”
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`LABELING
`1. We reserve comment on the proposed labeling until the application is otherwise adequate.
`If you revise labeling, your response must include updated content of labeling [21 CFR
`314.50(l)(1)(i)] in structured product labeling (SPL) format as described at
`http://www.fda.gov/oc/datacouncil/spl.html.
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`2. Please submit draft carton and container labeling revised as follows:
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` We ask that you revise the precautionary warning statement for phenylketonurics
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`• Add the following bolded statement or appropriate alternative to the carton and
`container labels per 21 CFR 208.24(d): "ATTENTION PHARMACIST: Each
`patient is required to receive the enclosed Medication Guide".
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`OTHER
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`Within one year after the date of this letter, you are required to resubmit or take one of the other
`actions available under 21 CFR 314.110. If you do not take one of these actions, we will consider
`your lack of response a request to withdraw the application under 21 CFR 314.65. A resubmission
`must fully address all the deficiencies listed. A partial response to this letter will not be processed
`as a resubmission and will not start a new review cycle.
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`Under 21 CFR 314.102(d), you may request a meeting or telephone conference with us to discuss
`what steps you need to take before the application may be approved. If you wish to have such a
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`(b) (4)
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`(b) (4)
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`(b)
`(4)
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`NDA 22-255
`Page 3
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`meeting, submit your meeting request as described in the FDA Guidance for Industry Formal
`Meetings With Sponsors and Applicants for PDUFA Products, February, 2000
`(http://www.fda.gov/cder/guidance/2125fnl.htm).
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`The drug product may not be legally marketed until you have been notified in writing that this
`application is approved.
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`If you have any questions, call Jacqueline H. Ware, Pharm.D., Supervisory Regulatory Project
`Manager, at (301) 796-1160.
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`Sincerely,
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`{See appended electronic signature page}
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`Ellis F. Unger, M.D.
`Deputy Director (Acting)
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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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.
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` /s/
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`Ellis Unger
`10/28/2008 07:36:11 PM
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