CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
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`202514Orig1s000
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`OFFICE DIRECTOR MEMO
`
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`
`
`

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`NDA 202514
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`Page 1 of3
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`Office Director Decisional Memo — Second Review Cycle
`
`
`
`From
`
`Edward Cox, MD MPH
`
`Office Director Decisional Memo - Second Review
`Subject
`
`Cycle
`NDA 202514
`
`NDA/BLA #
`
`Su ilement #
`
`Applicant Name
`Date of re-Submission
`
`PDUFA Goal Date
`
`Merck Sharpe & Dohme Corp.
`13, 2012
`
`March 13,2012
`
`Proprietary Name /
`Established
`S i
`
`Name
`
`Zioptan
`taflu rost o .hthalmic solution
`
`Dosa_e Forms / Stren_ h
`
`o ohthalmic solution, sterile / 0.0015%
`
`Proposed Indication(s)
`
`for reducing elevated intraocular pressure in patients
`with o 0 en-an ‘ e ' laucoma or ocular h ‘0 ertension
`
`Material Reviewed/Consulted
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`OND Action Packa ' e, includin' :
`
`Names of disci I line reviewers
`
`
`
`Review
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`Microbiolo 3 Review
`
`Clinical Pharmacolo 3 Review
`
`CDTL Reviews
`
`Deputy Division Director’s
`Reviews
`
`Yon I-en Zhan , Phil Colan- e10
`Kassa A alew, Susan Tho u son, Jean Mulinde
`William Bo d
`
`Wiley Chambers
`
`Renata Albrecht
`
`OSE/DMEPA
`OND=Ofice ofNew Drugs
`DSI=Division of Scientific Investigations
`CDTIFCross—Discipline Team Leader
`0815: Office of Surveillance and Epidemiology
`DMEPA=Division ofMedication Emor Prevention and Analysis
`
`Denise Bau I , Todd Brides, Carol Hol uist
`
`Tafluprost is an analog of prostaglandin F20t developed for the treatment of elevated
`intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Other
`members of this class (prostaglandin F20: analogs) have been previously approved for this
`indication. Tafluprost 0.0015% has been approved in a number of other countries outside of
`
`Reference ID: 3086050
`
`

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`NDA 202514
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`Page 2 of3
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`the US in preservative—free or preservative containing formulations. The formulation that the
`applicant is seeking approval of in NDA 202514 is a preservative free formulation.
`
`The review team has reviewed the issues in detail in their respective disciplines with regards to
`the safety and efficacy of Zioptan (tafluprost ophthalmic solution) 0.0015%. For a detailed
`discussion of NDA 202514, the reader is referred to the individual discipline specific reviews.
`In addition Dr. Boyd’s Cross-Discipline Team Leader Memorandums from the first and
`second review cycles and Dr. Chambers’ Deputy Division Director Reviews from the first and
`second review cycles, Dr. Albrecht’s Division Director Reviews from the first and second
`review cycles and my review from the first cycle also summarize key issues in the NDA
`submission. This memorandum will focus on the deficiency from the first cycle. For a more
`detailed discussion of the issue, the reader is referred to the Product Quality Microbiology
`Review of January 17, 2012, and the reviews from the first cycle discussing this issue.
`
`This is the second review cycle for tafluprost. On November 7, 2011, a complete response
`letter was issued that noted the following product quality microbiology deficiency:
`
`Your NDA does notprovide assurance ofthe sterility ofthefinal drugproduct. While
`you have revised your
`(m4) processing validation protocol in your submission of
`October 27, 2011,
`"’"" filling
`procedures using this revised validation protocol. In the absence
`(we) we
`cannot determine that the product is sterile and safefor use.
`
`T0 address this deficiency, provide a report describing three consecutive successful
`(”processing simulations
`(am; that you will usefor manufacturing
`thegiggduct using the inspection and accountingprocedures provided in the revised
`processing validation protocol submitted in the October 27, 2011 amendment.
`
`The product quality microbiology reviewer has evaluated the data from the 3 consecutive
`m" processing simulations using the revised validation protocol that are provided in the
`January 13, 2012, re—submission. The product quality microbiology assessment is that the
`results are acceptable and the deficiency has been adequately addressed.
`'Ihey recommend
`approval from the product quality microbiology standpoint.
`
`The proposed proprietary name, Zioptan, has been re-assessed by the Division of Medication
`Error Prevention and Analysis ODMEPA). As described in the DMEPA review of
`February 9, 2012, the proprietary name Zioptan is found to be acceptable.
`
`The application for Zioptan (tafluprost ophthahnic solution) 0.0015% was not referred to an
`FDA advisory committee because it is a member of the class of ophthahnic prostaglandin
`analogs with similar potential risks and benefits as other members in this class. The benefits
`and risks of using prostaglandin analogs to treat elevated intraocular pressure have been
`previously discussed at a meeting of the Dermatologic and Ophthalmic Drugs Advisory
`Committee on December 8, 1995, and the safety profile of tafluprost did not raise any new
`significant safety issues. The design of the clinical studies was similar to other approved drugs
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`Reference ID: 3086050
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`

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`NDA 202514
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`
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`Page 3 of 3
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`in this class and we are not aware of any controversial issues that would benefit from further
`advisory committee discussion.
`
`With regard to the Pediatric Research Equity Act (PREA), the pediatric study requirement for
`this application is being waived because necessary studies are impossible or highly
`impracticable as there are too few children with this disease/condition to study.
`
`In summary, the deficiency from the first cycle regarding inadequate assurance of sterility has
`been adequately addressed. The review team recommends approval. I agree with the review
`team’s recommendation. The application for Zioptan (tafluprost ophthalmic solution)
`0.0015% for reducing elevated intraocular pressure in patients with open-angle glaucoma or
`ocular hypertension should be issued an Approval letter.
`
`Reference ID: 3086050
`
`

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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/
`----------------------------------------------------
`
`EDWARD M COX
`02/10/2012
`
`Reference ID: 3086050
`
`