CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`202514Orig1s000
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`OTHER ACTION LETTERS
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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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`NDA 202514
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`COMPLETE RESPONSE
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`Merck Sharp & Dohme Corp.
`Attention: Chitkala Kalidas, Ph.D.
`Director, Worldwide Regulatory Affairs
`P.O. Box 2000, RY33-204
`Rahway, New Jersey 07065-0900
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`Dear Dr. Kalidas:
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`Please refer to your New Drug Application (NDA) dated and received January 7, 2011,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for ZIOPTAN
`(tafluprost ophthalmic solution) 0.0015%.
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`We acknowledge receipt of your amendments dated:
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`January 7, 2011 (2)
`February 17, 2011
`March 29, 2011
`April 28, 2011
`May 11, 2011
`June 9, 2011
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`June 30, 2011
`July 11, 2011
`August 3, 2011
`August 22, 2011
`September 13, 2011
`October 26, 2011
`November 3, 2011
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`We have completed our review of this application, as amended, and have determined that we
`cannot approve this application in its present form. We have described our reasons for this
`action below and, where possible, our recommendations to address these issues.
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`PRODUCT QUALITY MICROBIOLOGY
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`Your NDA does not provide assurance of the sterility of the final drug product. While you have
`revised your
` processing validation protocol in your submission of October 27, 2011,
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`January 20, 2011
`February 28, 2011
`April 4, 2011
`April 29, 2011
`May 24, 2011
`June 10, 2011
`July 5, 2011
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`July 26, 2011
`August 10, 2011
`September 2, 2011
`September 27, 2011
`October 27, 2011
`November 4, 2011
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`February 9, 2011
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`March 23, 2011
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`April 6, 2011
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`May 6, 2011
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`June 8, 2011
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`June 13, 2011
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`July 6, 2011
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`August 1, 2011
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`August 12, 2011
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`September 6, 2011
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`October 13, 2011
`November 2, 2011 (2)
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`Reference ID: 3040894
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`(b) (4)
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`(b) (4)
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`NDA 202514
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`Page 2
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`validation protocol. In the absence
`sterile and safe for use.
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`(m4) filling procedures using this revised
`(m4), we cannot determine that the product is
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`(m4)
`To address this deficiency, provide a report describing three consecutive successful
`processing simulations
`(we) that you will use for manufacturing the product using
`the inspection and accounting procedures provided in the revised
`(m4) processing validation
`protocol submitted in the October 27, 2011 amendment.
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`SAFETY UPDATE
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`When you respond to the above deficiencies, include a safety update as described at
`21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all non-clinical and
`clinical studies/trials of the drug under consideration regardless of indication, dosage form, or
`dose level.
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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 other actions
`available under 21 CFR 314.110. Ifyou do not take one of these actions, we may consider your
`lack of response a request to withdraw the application under 21 CFR 314.65. You may also
`request an extension of time in which to resubmit the application. 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 meeting, submit your meeting request as described in the FDA’s “Guidance for Industry -
`Formal Meetings Between the FDA and Sponsors or Applicants,” May 2009 at
`hm;://www.fda.gov/downloads/Drugs/GuidanceComplianceReglilatOQInformation/Guidances/U
`CM1 5 3222 .pdf.
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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, please call Constantine J. Markos, B.S., Pharm.D., R.Ph., Regulatory
`Health Project Manager, at (301) 796-1600.
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`Sincerely,
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`{See appended electronic signature page}
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`Edward M. Cox, M.D., M.P.H.
`Director
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`Office of Antimicrobial Products
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`Center for Drug Evaluation and Research
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`Reference ID: 3040894
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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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`EDWARD M COX
`11/07/2011
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`Reference ID: 3040894
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