`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`202514Orig1s000
`
`
`ZIOPTAN
`
`tafluprost ophthalmic solution, 0.0015%.
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`Merck Sharp & Dohme Corp.
`
`February10, 2012
`
` For the reduction of elevated intraocular pressure
`(IOP) in patients with open-angle glaucoma or ocular
`hypertension.
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`202514Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`X
`X
`
`X
`X
`X
`X
`X
`X
`
`X
`X
`X
`X
`X
`
`X
`X
`
`

`

`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202514Orig1s000
`
`APPROVAL LETTER
`
`

`

`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`NDA 202514
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring, MD 20993
`
`NDA APPROVAL
`
`
`
`Merck Sharp & Dohme Corp.
`Attention: Chitkala Kalidas, Ph.D.
`Director, Worldwide Regulatory Affairs
`P.O. Box 2000, RY33-204
`Rahway, New Jersey 07065-0900
`
`
`Dear Dr. Kalidas:
`
`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%.
`
`We acknowledge receipt of your amendments dated:
`
`January 7, 2011 (2)
`January 20, 2011
`February 28, 2011
`April 4, 2011
`April 29, 2011
`May 24, 2011
`June 10, 2011
`July 5, 2011
`
`July 26, 2011
`August 10, 2011
`September 2, 2011
`September 27, 2011
`October 27, 2011
`November 7, 2011
`January 13, 2012
`
`The January 13, 2012, submission constituted a complete response to our November 7, 2011,
`action letter.
`
`This new drug application provides for the use of ZIOPTAN (tafluprost ophthalmic solution) for
`the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or
`ocular hypertension.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`January 10, 2011
`
`February 9, 2011
`
`March 23, 2011
`
`April 6, 2011
`
`May 6, 2011
`
`
`June 8, 2011
`
`
`June 13, 2011
`
`July 6, 2011
`
`
`August 1, 2011
`
`August 12, 2011
`
`September 6, 2011
`
`October 13, 2011
`November 2, 2011 (2)
`December 6, 2011
`
`January 23, 2012
`
`January 14, 2011
`February 17, 2011
`March 29, 2011
`April 28, 2011
`May 11, 2011
`June 9, 2011
`June 30, 2011
`July 11, 2011
`August 4, 2011
`August 22, 2011
`September 13, 2011
`October 26, 2011
`November 3, 2011
`December 7, 2011
`
`Reference ID: 3086096
`
`

`

`NDA 202514
`Page 2
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling text for the package insert and patient
`package insert. Information on submitting SPL files using eLIST may be found in the guidance
`for industry titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton, container and pouch labels that are identical to the enclosed carton,
`container and pouch labels submitted on November 4, 2011, 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 (June 2008).” 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, Container and Pouch Labels for approved
`NDA 202514.” Approval of this submission by FDA is not required before the labeling is used.
`
`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an un-approved new drug.
`
`Your application for ZIOPTAN was not referred to an FDA advisory committee because it is a
`member of the class of ophthalmic 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 clinical study design was similar
`to other approved drugs in this class and we are not aware of any controversial issues that would
`benefit from further advisory committee discussion.
`
`
`
`
`
`
`
`Reference ID: 3086096
`
`

`

`NDA 202514
`Page 3
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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 in-applicable.
`
`We are waiving the pediatric study requirement for this application because necessary studies are
`impossible or highly impracticable as there are too few children with this disease/condition to
`study.
`
`PROMOTIONAL MATERIALS
`
`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:
`
`
`U.S. Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`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 Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`MEDWATCH-TO-MANUFACTURER PROGRAM
`
`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at
`http://www.fda.gov/Safety/MedWatch/HowToReport/ucm166910.htm.
`
`
`Reference ID: 3086096
`
`

`

`NDA 202514
`Page 4
`
`POST-ACTION FEEDBACK MEETING
`
`New molecular entities and new biologics qualify for a post-action feedback meeting. Such
`meetings are used to discuss the quality of the application and to evaluate the communication
`process during drug development and marketing application review. The purpose is to learn
`from successful aspects of the review process and to identify areas that could benefit from
`improvement. If you would like to have such a meeting with us, call the Regulatory Health
`Project Manager for this application.
`
`If you have any questions, please call Constantine J. Markos, B.S., Pharm.D., R.Ph., Regulatory
`Health Project Manager, at (301) 796-3871.
`
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Edward M. Cox, M.D., M.P.H.
`Director
`Office of Antimicrobial Products
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`
`
`
`ENCLOSURE(S): Content of Labeling (Package Insert and Patient Package Insert)
`
`
` Carton, Container and Pouch Labels
`
`Reference ID: 3086096
`
`

`

`---------------------------------------------------------------------------------------------------------
`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: 3086096
`
`