CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`202514Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Direct-to-Consumer Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`November 3, 2011
`
`
`To:
`
`
`From:
`
`Subject:
`
`Hyun Son, Senior Regulatory Management Officer, DTOP
`
`Adora Ndu, Regulatory Review Officer, DDTCP
`
`NDA 202514
`DDTCP comments for ZIOPTAN™ (tafluprost ophthalmic solution)
`0.0015%
`Patient Package Insert (PPI)
`
`
`
`
`
`
`
`
`DDMAC has reviewed the proposed Patient Package Insert (PPI) for ZIOPTAN™
`(tafluprost ophthalmic solution) 0.0015%, submitted for consult on November 1, 2011,
`and offers the following comments.
`
`The version of the draft PPI used in this review is titled, “Zioptan PPI (clean)” received
`from DRISK on November 3rd, 2011.
`
`If you have any questions on the patient labeling, please contact Adora Ndu at
`301-796-5114 or adora.ndu@fda.hhs.gov.
`
`
`
`
`
`
`1
`
`Reference ID: 3039385
`
`8 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ADORA E NDU
`11/03/2011
`
`Reference ID: 3039385
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy Initiatives
`Division of Medical Policy Programs
`
`PATIENT LABELING REVIEW
`
`November 3, 2011
`Renata Albrecht, MD, Director
`Division of Special Pathogens and Transplant Products
`(DSPTP)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs (DMPP)
`
`Melissa Hulett, RN, BSN, MSBA
`Team Leader, Patient Labeling Team
`Division of Medical Policy Programs
`
`Sharon W. Williams, MSN, BSN, RN
`Patient Labeling Reviewer
`Division of Medical Policy Programs
`DMPP Review of Patient Labeling (Patient Package Insert)
`
`Date:
`To:
`
`Through:
`
`From:
`
`Subject:
`Drug Name (established
`name):
`
`ZIOPTAN (tafluprost) 0.0015%
`
`Dosage Form and Route: Ophthalmic solution
`Application
`Type/Number:
`Applicant:
`OSE RCM #:
`
`
`202514
`Merck Sharp and Dohme Corp
`2011-4182
`
`
`
`
`
`
`Reference ID: 3039183
`
`1
`
`

`

` 1
`
`
`
`INTRODUCTION
`This review is written in response to a request by the Division of Transplant and
`Ophthalmology Prodcuts (DTOP) for the Division of Medical Policy Programs
`(DMPP) to review the Applicant’s proposed Patient Package Insert (PPI) for
`ZIOPTAN (tafluprost) 0.0015%.
`The purpose of the Applicant’s submission is to approval of a new drug application
`for ZIOPTAN (tafluprost) 0.0015% a preservative-free ophthalmic formulation
`indicated for the treatment of elevated intra-ocular pressure in open angle glaucoma
`or ocular hypertension.
`
`2 MATERIAL REVIEWED
`• Draft ZIOPTAN (tafluprost) 0.0015% Patient Package Insert (PPI) received on
`January 7, 2011, revised by the Review Division throughout the review cycle and
`received by DMPP on November 2, 2011
`• Draft ZIOPTAN (tafluprost) 0.0015% Prescribing Information (PI) received
`January 7, 2011, revised by the Review Division throughout the current review
`cycle and received by DMPP on November 2, 2011
`
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level. In our review of the PPI the target
`reading level is at or below an 8th grade level.
`
`
`
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss. We have reformatted the PPI document
`using the Verdana font, size 11.
`In our review of the PPI we have:
`•
`simplified wording and clarified concepts where possible
`•
`ensured that the PPI is consistent with the prescribing information (PI)
`•
`removed unnecessary or redundant information
`•
`ensured that the PPI meets the criteria as specified in FDA’s Guidance for
`Useful Written Consumer Medication Information (published July 2006)
`
`
`
`
`
`
`
`Reference ID: 3039183
`
`2
`
`

`

`4 CONCLUSIONS
`The PPI is acceptable with our recommended changes.
`
`5 RECOMMENDATIONS
`• Please send these comments to the Applicant and copy DMPP on the
`correspondence.
`• Our annotated versions of the PPI are appended to this memo. Consult DMPP
`regarding any additional revisions made to the PI to determine if corresponding
`revisions need to be made to the PPI.
` Please let us know if you have any questions.
`
`
`
`
`
`Reference ID: 3039183
`
`3
`
`20 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this
`page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SHARON W WILLIAMS
`11/03/2011
`
`MELISSA I HULETT
`11/03/2011
`
`LASHAWN M GRIFFITHS
`11/03/2011
`
`Reference ID: 3039183
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`Division of Professional Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`October 19, 2011
`
`
`To:
`
`
`
`Constantine Markos, B.S., Pharm.D., R.Ph., Regulatory Health
`Project Manager
`Division of Transplant and Ophthalmology Products
`
`Christine Corser, Pharm.D., Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`Division of Professional Promotion (DPP)
`
`
`
`
`
`From:
`
`
`
`
`Subject:
`
`NDA 202514
`ZIOPTAN (tafluprost ophthalmic solution) 0.0015%
`
`
`
`
`
`As requested in your consult dated June 6, 2011, the Office of Prescription Drug
`Promotion (OPDP) has reviewed the draft labeling for ZIOPTAN (tafluprost
`ophthalmic solution) 0.0015%.
`
`OPDP’s comments are based on the substantially complete version of the
`labeling titled, “N202514_Label1.doc” which was sent via email from Constantine
`Markos on October 17, 2011.
`
`OPDP’s comments on the PI are attached in the substantially complete version
`of the labeling. Please note that the Division of Professional Promotion (DPP)
`reviewed the PI.
`
`If you have any questions about DPP’s comments on the PI, please contact
`Christine Corser at 6-2653 or at christine.corser@fda.hhs.gov.
`
`Thank you for the opportunity to provide comments.
`
`
`
`Reference ID: 3030960
`
`1
`
`7 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this
`page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`CHRISTINE G CORSER
`10/19/2011
`
`Reference ID: 3030960
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`August 23, 2011
`
`NDA 202514
`
`Todd Bridges, RPh, Team Leader
`Carol Holquist, RPh, Director
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`Denise V. Baugh, PharmD, BCPS, Safety Evaluator
`Division of Medication Error Prevention and Analysis
`(DMEPA)
`
`Label and Labeling Review
`Saflutan (Tafluprost) Ophthalmic Solution
`0.0015%
`
`Merck Sharp & Dohme Corp.
`
`2011-136
`
`Date:
`
`Application
`Type/Number:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name(s):
`
`Applicant:
`
`OSE RCM #:
`
`
`
`
`
`
`Reference ID: 3004827
`
`1
`
`

`

`1
`INTRODUCTION
`This review evaluates the labels and labeling of Saflutan (Tafluprost) Ophthalmic
`Solution for their vulnerability to medication errors in response to a request from the
`Division of Transplant & Ophthalmologic Products (DTOP).
`2 METHODS AND MATERIALS
`Using Failure Mode and Effects Analysis1 , the Division of Medication Error Prevention
`and Analysis (DMEPA) evaluated the container label, pouch and carton labeling
`submitted by the Applicant on January 7, 2011, (See Appendix A; no image of insert
`labeling). We requested (via correspondence dated March 8, 2011) the Applicant submit
`a prototype of the proposed LDPE container for our review.
`3 DISCUSSION
`
`4 CONCLUSIONS AND RECOMMENDATIONS
`The information on the label and labeling can be clarified and improved upon to
`minimize the potential for re-use of the LDPE vial once opened. Section 4.1 (Comments
`to the Division) contains our recommendations for the insert labeling. Section 4.2
`(Comments to the Applicant) contains our recommendations for the container labels,
`
`
`1 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004.
`
`Reference ID: 3004827
`
`
`2
`
`(b) (4)
`
`

`

`carton and pouch labeling. We request these recommendations be communicated to the
`Applicant prior to approval of this NDA.
`
`Please copy the Division of Medication Error Prevention and Analysis on any
`communication to the Applicant with regard to this review. If you have further questions
`or need clarifications, please contact Karen Townsend, OSE Project Manager, at 301-
`796—5413.
`
`4.1
`
`COMMENTS TO THE DIVISION
`
`Delete the statement,
`mosage and Administration) under the heading “Full Prescribing Information” as
`this may result in patients inappropriately treating both eyes or saving the
`remaining contents of the container for future doses (which may increase the risk
`of bacterial contamination of the solution since it is a preservative-free product).
`
`we)” in Section 2
`
`4.2
`
`COMMENTS TO THE APPLICANT
`
`A.
`
`Carton and Pouch Labeling (Trade and Professional)
`
`1.
`
`Delete the statement,
`from all labeling as this may result in patients inappropriately
`treating both eyes or saving the remaining contents of the container for
`future doses (which may increase the risk of bacterial contamination of the
`solution since it is a preservative-free product).
`
`00(4)
`
`Decrease the size of the pink and orange graphic that appears above the
`proprietary name.
`
`Revise the established name (including dosage form) presentation to be in
`accordance with 21 CFR 201.10(g)(2) which states “The established name
`shall be printed in letters that are at least half as large as the letters
`comprising the proprietary name or designation with which it is joined,
`and the established name shall have a prominence commensurate with the
`prominence with which such proprietary name or designation appears,
`taking into account all pertinent factors, including typography, layout,
`contrast and other printing features.”
`
`M”
`Follow the statement, ‘Single-Use Container’ with
`This product contains no preservative and must be thrown away
`
`after use.
`
`Increase the prominence of the product strength so this information is
`more visible.
`
`(m4)
`
`Reference ID: 3004827
`
`

`

`
`
`Pouch Labeling (Trade and Professional)
`1.
`Unbold the statements, ‘Sterile’ and ‘Preservative-Free’ as these
`
`statements are more prominent than the established name.
`
`2.
`Relocate the entire
` statement to appear just before the
`
`manufactured for statement so that the other statements can move up and
`
`have more prominence.
`Carton Labeling
`1.
`Decrease the size of the orange triangular graphic located in the upper left hand
`
`corner and the pink triangular graphic located in the lower right hand corner
`
`both of which are located on the principal display panel.
`2.
`Relocate the
` to the principal display panel beneath the
`
`statement, ‘Refrigerate’.
` statement to the back panel.
`3.
`Relocate the entire
`4.
`Un-bold and re-locate the statement,
`
`panel.
`
` to the back
`
`B.
`
`
`
`
`
`C.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3004827
`
`
`4
`
`6 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`DENISE V BAUGH
`08/23/2011
`
`TODD D BRIDGES
`08/23/2011
`
`CAROL A HOLQUIST
`08/24/2011
`
`Reference ID: 3004827
`
`

`

`NDA# 202514
`
`Page 1 of 16
`
`RPM FILING REVIEW
`
`(Including Memo of Filing Meeting)
`To be completed for all new NDAs, BLAs, and Efficacy Supplements [except SE8 (labeling
`change with clinical data) and SE9 (manufacturing change with clinical data]
`
`WW ——
`
`A lication Information
`
`Proprietary Name: Pending
`Established/Proper Name: tafluprost
`Dosage Form: Ophthalmic Drops
`Stren ths: 0.0015%
`
`Applicant: Merck Sharp & Dohme Corp.
`A cut for A licant if a licable :
`
`Date of Application: 01/07/2011
`Date of Receipt: 01/07/2011
`Date clock started afier UN: N/A
`
`PDUFA Goal Date: 11/07/2011
`
`Action Goal Date (if different):
`10/07/2011
`
`
`
`Filin Date: 03/08/2011
`
`Date of Filin Meetin: 02/16/2011
`
`Chemical Classification: 1.2.3 etc. ori
`
`' Ial NDAs on]
`
`1
`
`Proposed indication(s)/Proposed change(s): Reduction of elevated intra—ocular pressure (IOP) in
`open—angle glaucoma or ocular hypertension.
`
`Type of Original NDA:
`AND (if applicable)
`Type of NDA Supplement:
`
`If505(b)(2): Drafl the “505(b)(2) Assessment”form found at:
`h
`://inside. do. ov:9003/CDER/0 ceo 'ewDru s/ImmediateO ce/UCM02 7499
`and re er to A I endixA or urther in ormation.
`
`Review Classification:
`
`Ifthe application includes a complete response to pediatric WR, review
`classification is Priority.
`
`X 505(b)(l)
`I] 505(b)(2)
`I 505(b)(l)
`El 505000)
`
`X Standard
`
`Dmmw
`
`Ifa tropical diseasepriority review voucher was submitted, review
`classification is Priority.
`
`E] Tropical Disease Priority
`Review Voucher submi“ed
`
`Resubmission alter withdrawal? I
`
`Resubmission after refuse to file? I
`
`Part 3 Combination Product? I
`
`Ifyes, contact the Oflice of Combination
`Products (OCP) and copy them on all Inter-
`Center consults
`
`I Convenience kit/Co-package
`E] Pre-filled drug delivery device/system
`Pre-filled biologic delivery device/system
`Device coated/unpregnated/combined with drug
`Device coated/unpregnated/combined with biologic
`Drug/Biologic
`Separate products requiring cross-labeling
`Possible combination based on cross-labeling of separate
`roducts
`'U
`Other dru device/biolo ical
`El
`
`EIEIEIEIEIEI
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`1
`
`

`

`NDA# 202514
`
`Page 2 of 16
`
`
`
`E] Fast Track
`El Rolling Review
`E] Orphan Designation
`
`E] Rx-to-OTC switch. Full
`E] Rx-to-OTC switch, Partial
`I:] Direct-to—OTC
`
`Other:
`
`E] PMC response
`E] PMR response:
`El FDAAA [505(0)]
`El PREA deferred pediatric studies [21 CFR
`314.55(b)/21 CFR 601.27(b)]
`El Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
`El Animal rule post-marketing studies to verify clinical
`benefit and safe
`21 CFR 314.610/21 CFR 601.42
`
`Collaborative Review Division (if OTC product):
`
`List referenced IND Number(s): 062690
`
`Goal Dates/Product Names/Classification Pro - rties
`
`PDUFA and Action Goal dates correct in tracking system?
`
`Ifno, ask the document room staff'to correct them immediately.
`These are the dates used or calculating ins
`
`Are the proprietary. estabhshed/proper. and applicant names
`correct in tracking system?
`
`Ifno, ask the document room staffto make the corrections. Also,
`ask the document room staffto add the establishedélroper name
`to the supporting IND(s) ifnot already entered into tracking
`5 stem.
`
`Is the review priority (S or P) and all appropriate
`classifications/properties entered into tracking system (e.g.,
`chemical classification. combination product classification,
`505(b)(2), orphan drug)? For NDAsflVDA supplements, check
`the Application and Supplement Notification Checklistsfor a list
`ofall classifications/properties at:
`://inside. do. ov:9003/CDER/0 ceo usinessProcessSu
`m
`
`ort/ucm163970Jlt
`
`Ifno, ask the document room staffto make the appropriate
`entries.
`
`A lication Int _ri Polic
`
`Comment
`
`Is the application affected by the Application Integrity Policy
`(AIP)? Check the AIP list at:
`h mix/fil'ml do. ov/ICECI/En orcementActions/A IicationInte
`Ifyes explainrn connnent column.
`
`'
`
`'I’oIi
`
`
`
`/de unit
`
`.-
`
`If affected by AIP. has OC/DMPQ been notified of the
`submission? If yes, date notified:
`—mm
`Is Form 3397 (User Fee Cover Sheet) included with
`authorized signature?
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`2
`
`

`

`NDA# 202514
`
`Page 3 of 16
`
`
`User Fee Status
`
`Payment for this application:
`
`Ifa userfee is required and it has not been paid (and it X Paid
`is not exempted or waived), the application is
`E] Exempt (orphan. government)
`unacceptableforfilingfollowing a 5-day graceperiod. D Waived (C.8.. small business‘ public health)
`Review stops. Send Unacceptablefor Filing (UN) letter B Not required
`and contact userfee stafl.‘
`
`Payment of other user fees:
`
`X Not in meal-s
`Ifthefirm is in arrearsfor otherfees (regardless of
`whether a userfee has been paidfor this application), D In wears
`the application is unacceptableforfiling (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the user ee stai .
`
`IAs/NDA Effica Su lements o
`
`mill—
`Is the application for a duplicate ofa listed drug and eligible --I_
`
`for a roval under section 505 ') as an ANDA?
`Is the application for a duplicate of a listed drug whose only
`difference is that the extent to which the active ingredient(s)
`is absorbed or otherwise made available to the site of action
`
`
`
`is less than that of the reference listed drug (RLD)? [see 21
`CFR 314.54 u
`
`Is the application for a duplicate of a listed drug whose only
`difi‘erence is that the rate at which the proposed product’s
`active ingredient(s) is absorbed or made available to the site
`of action is unintentionally less than that of the listed drug
`[see 21 CFR 314.54(b)(2)]?
`
`Ifyou answered yes to any ofthe above questions, the application
`may be refusedforfiling under 21 CFR 314.101(d)(9). Contact
`
`the (b)(2) review stafl'in the Immediate omce ofNew Drugs
`Is there unexpired exclusivity on the active moiety (e.g., 5-
`year, 3-year, orphan or pediauic exclusivity)?
`Check the Electronic Orange Book at:
`h@://www.accessdata.(do.gov/scriets/cder/ob/detault.ctm
`
`If es, lease list below:
`
`Ifthere is unexpired, 5—year exclusivitv remaining on the active moietyfor the proposed drugproduct, a 505(b)(2)
`application cannot be submitted until the period ofexclusivity expires (unless the applicantprovides paragraph IV
`patent certification; then an application can be submittedfour years afier the date ofapproval.) Pediatric
`erclush'ity will attend both ofthe timefi'ames in this provision by 6 months. 21 CFR 108(b)(2). Unevpired, 3-year
`
`Does another product (same active moiety) have orphan
`exclusivity for the same indication? Check the Orphan Drug
`Designations and Approvals list at:
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`3
`
`

`

`NDA# 202514
`
`Page 4 of 16
`
`
`
`If another product has orphan exclusivity, is the product
`considered to be the same product according to the orphan
`drug definition of sameness [see 21 CFR 316.3(b)(13)]?
`
`X
`
`Ifyes, consult the Director, Division ofRegulatory Policy II,
`0] Ice 0 Re nlato Poli
`v
`
`Has the applicant requested 5-year or 3-year Waxman-Hatch
`exclusivity? (NDAsAVDA eflicaqi supplements only)
`
`If yes. # years requested:
`
`Note: An applicant can receive exclusivitv without requesting it;
`there are, re nestin exclusivitv is not re aired.
`
`Is the proposed product a single enantiomer of a racemic drug
`previously approved for a different therapeutic use (NDAs
`on] )?
`
`If yes, did the applicant: (a) elect to have the single
`enantiomer (contained as an active ingredient) not be
`considered the same active ingredient as that contained in an
`already approved racemic drug, and/or (b): request
`exclusivity pursuant to section 505(u) of the Act (per
`
`OGD/DLPS/LRB.
`
`Format and Content
`
`I All paper (except for COL)
`X All electronic
`
`Do not check mixed submission ifthe only electronic component B IVIiXCd (paper/electronic)
`is the content oflabeling (COL).
`
`X CTD
`
`El Non-CTD
`
`If mixed (paper/electronic) submission, which parts of the
`a lication are submitted in electronic format?
`
`FDAAA Section 1 1 l3)? Ifyes, contact Mary Ann Holovac, Director ofDrug Information,
`
`Overall Format/Content
`
`Ifelectronicsubmission,doesitfollowtheeCTD IIIC-
`
`mm-_
`
`Index. Does the submission contain an accurate
`com .rehensive index?
`
`Is the submission complete as required under 21 CFR 314. 50
`(NDAs/NDA eflicacy supplements) or under 21 CFR 601.2
`
`
`
`://www fda. ov/downloads/Dru s/GuidanceCon lianceReh lato Information/Guidances/ucn1072349.
`
`
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`4
`
`

`

`NDA# 202514
`
`Page 5 of 16
`
`
`X legible
`X English (or translated into English)
`X pagination
`X navigable hyperlinks (electronic submissions only)
`
`If no. exlain.
`
`BLAs only: Companion application received if a shared or
`divided manufactming arrangement?
`
`If es. BLA #
`Forms and Certifications
`
`Electronicforms and certifications with electronic signatures (scanned, digital, or electronic — similar to BARTS,
`e.g., /s/) are acceptable. Otherwise,paperforms and certifications with hand-written signatures nmst be included.
`Farms include: userfee cover sheet (3397), application form (356h), patent information (3542a), financial
`disclosure (3454/3455), and clinical trials (3674); Certifications include: debannent certification, patent
`certi cation(s), eld covcerti cation, and ediatric certi cation.
`A Ilication Form
`Is form FDA 356h included with authorized signature per 21
`CFR 314.50(a)?
`
`2mm
`
`NA Comment
`
`5
`
`Ifforeign applicant, a US. agent must sign theform [see 21 CFR
`
`Are all establishments and their registration numbers listed
`on the form/attached to the form?
`
`Patent Information
`IAs/NDA eflicac su lements o
`
`Is patent information submitted on form FDA 35423 per 21
`CFR 314.53(c)?
`
`Financial Disclosure
`Are financial disclosure fomis FDA 3454 and/or 3455
`
`m
`
`included with authorized signature per 21 CFR 54.4(a)(1) and
`(3)?
`
`Forms must be signed by the APPLICANT, not an Agent [see 21
`CFR 54.2(g)].
`
`Note: Financial disclosure is requiredfor bioequiralence studies
`that are the basis or a I roral.
`
`Clinical Trials Database
`
`Is form FDA 3674 included with authorized signature?
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Form 36 74. ”
`
`Ifno, ensure that language requesting submission oftheform is
`included in the acknowledgement letter sent to the a licant
`Debarment Certification
`Is a correctly worded Debarment Certification included with
`authorized si n ature?
`
`m
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`

`

`NDA# 202514
`
`Page 6 of 16
`
`
`Certification is not requiredfor supplements if'submitted in the
`original application; Ifforeign applicant, bo_th the applicant and
`the US. Agent must sign the certification filer Guidancefor
`Industry: Submitting Debarment Certifications].
`
`Note: Debarment Certification should use wording in FDCA
`Section 306(k)(1) i.e., “[Name ofapplicant] hereby certifies that it
`did not and will not use in any capacity the services ofany person
`debarred under section 306 ofthe Federal Food, Drug, and
`Cosmetic Act in connection with this application. " Applicant may
`not use wordin ' such as, "To the best 0 mv knowled_ e... "
`
`Field Copy Certification
`IAs/NDA effica
`sn. Ilements on]
`
`NA Comment
`
`For paper submissions only: Is a Field Copy Certification
`(that it is a true copy of the CMC technical section) included?
`
`Field Copy Certification is not needed if”there is no CMC
`technical section or ifthis is an electronic submission (the Field
`Office has access to the EDR)
`
`Ifmaroon field copyjacketsfrom foreign applicants are received,
`'
`to the a ro riate (dd 0) Ice.
`
`Controlled Substance/Product with Abuse Potential mm__
`X
`
`Is an Abuse Liability Assessment. including a proposal for
`scheduling. submitted per 21 CFR 314.50(d)(5)(vii)?
`
`Ifyes, date consult sent to the Controlled Substance Stafl:
`
`For non-NMEs:
`
`Date ofconsult sent to Controlled Substance Stafl :
`
`
`
`—_m
`PREA
`X
`
`Does the application nigger PREA?
`
`Ifyes, notifj’PeRC RPM (PeRC meeting is required):
`
`Note: NDAs/BLAs/eflicacv supplementsfor new active ingredients,
`new indications, new dosagefomls, new dosing regimens, or new
`routes ofadministration trigger PREA. All waiver & deferral
`requests, pediatric plans, andpediatric assessment studies must be
`reviewed bv PeRC Irior to m roval o the m IIlication/su I lenient.
`
`If the application triggers PREA, are the required pediatric
`assessment studies or a full waiver of pediauic studies
`included?
`
`
`
`2h ://inside fda. ovz9003/CDER/OfficeofNeme s/Pediatn'candMatemalHealthStaff/ucmOZ7829.htm
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`6
`
`

`

`NDA# 202514
`
`Page 7 of 16
`
`
`If studies or full waiver not included, is a request for full
`waiver of pediatric studies OR a request for partial waiver
`and/or deferral with a pediatric plan included?
`
`X
`
`I no, reuest in 74-d
`
`letter
`
`If a request for full waiver/partial waiver/deferral is
`included, does the application contain the certification(s)
`required by FDCA Section 505B(a)(3) and (4)?
`
`I no, reuest in 74-da * letter
`
`BPCA (NDAs/NDA efficacy supplements only):
`
`Is this submission a complete response to a pediatric Written
`Request?
`
`Ifyes, notify Pediatric Exclusivity Board RPM (pediatric
`exclusivi determination is re r uired)3
`-_mm
`Is a proposed proprietary name submitted?
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Proprietary Name/Requestfor
`Review.”
`
`_mm
`Is a REMS submitted?
`
`Ifyes, send consult to OSE/DRISK and notify OC/DCRMS via
`the DCRMSRAlP mailbox
`
`Prescri ntion Labelin_
`Check all types of labeling submitted.
`
`D Not applicable
`X Package Insert (PI)
`X Patient Package Insert (PPI)
`D Instructions for Use (IFU)
`I] Medication Guide (MedGuide)
`X Carton labels
`X Immediate container labels
`
`I] Diluent
`
`format?
`
`Is Electronic Content of labeling (COL) submitted in SPL
`
`://inside fda. ov:9003/CDER/OfficeofNewDru s/Pediatn'candMatemalI-IealthStaff/ucmOZ7837.htm
`3h
`4
`
` h ://inside fda. ovz9003/CDER/OfficeoiNeme s/Stud End intsandLabelin evelo mentTeam/ucmO
`
`25576.htm
`
`
`
`
`
`Version: 02/03/2011
`
`Reference ID: 2971625
`
`7
`
`

`

`NDA# 202514
`
`Page 8 of 16
`
`
`
`If PI not submitted in PLR format, was a waiver or
`
`X
`
`deferral requested before the application was received or in
`the submission? If requested before application was
`submitted. what is the status of the request?
`
`I no waiver or de ermI, re uest PLR ormat in 74-day letter.
`
`container labels) consulted to DDMAC?
`
`.-
`
`MedGuide. PPI. IFU (plus PI) consulted to OSE/DRISK?
`(send WORD version Ifavailable)
`
`Carton and immediate container labels. PI. PPI sent to
`
`OSE/DMEPA and appropriate CMC review office (OBP or
`ONDQA)?
`
`OTC Labelin_
`Check all types of labeling submitted.
`
`X Not Applicable
`I Outer carton label
`I] Immediate container label
`E] Blister card
`I] Blister backing label
`El Consumer Information Leaflet (ClL)
`I] Physician sample
`I:I Consumer sample
`I] Other 5 eci
`—EEIEI-—
`
`Iselectronic contentoflabeling(COL) submitted? I..-
`
`I no, reuest in 74-4 ¢
`
`7 letter.
`
`Date(s): 08/24/2009
`
`Are annotated specifications submitted for all stock keeping
`units (SKUs)?
`
`If representative labeling is submitted. are all represented
`SKUs defined?
`
`I no, reuest in 74-411 7 letter.
`
`All labeling/packaging. and current approved Rx PI (if
`switch) sent to OSE/DMEPA?
`Other Consults
`Are additional consults needed? (e.g.. IFU to CDRH; QT
`study report to QT Interdisciplinary Review Team)
`
`Emma-—
`
`eci‘ consult s and date 3 sent:
`_—mmn
`End—of Phase 2 meeting(s)?
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`8
`
`

`

`NDA# 202514
`
`Page 9 of 16
`
`
`Pre-NDA/Pre-BLA/Pre—Supplement meeting(s)?
`X
`Date(s): 08/13/2010
`
`I yes, distribute minutes be are 11in meetin
`
`Any Special Protocol Assessments (SPAS)?
`Date-(s);
`
`meeting
`
`Ifyes, distribute letter and/or relevant minutes beforefiling
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`9
`
`

`

`NDA# 202514
`
`Page 10 of 16
`
`ATTACHMENT
`
`MEMO OF FILING MEETING
`
`DATE: 02/16/2011
`
`BLAINDA/Supp #: 202514
`
`PROPRIETARY NAME: Pending
`
`ESTABLISHED/PROPER NAME: tafluprost
`
`DOSAGE FORM/STRENGTH: Ophthalmic Drops, 0.0015%
`
`APPLICANT: Merck Sharp & Dohme Corp.
`
`PROPOSED lNDICATION(S)/PROPOSED CHANGE(S): Reduction of elevated
`
`intra—ocular pressure (IOP) in open—angle glaucoma or ocular hypertension.
`
`BACKGROUND: IND 062690; EOP2 Meeting held on 08/24/2009; Pre—NDA Meeting held
`on 08/13/2010.
`
`REVIEW TEAM:
`
`Discipline/Organization
`
`Regulatory Project Management
`
`Constantine J. Markos
`
`CPMSs/ILS: Maureen P. Dillon—Parker
`Judit Milstein
`
`Cross—Discipline Team Leader
`(CDTL)
`
`William M. Boyd
`
`“m“
`
`or
`
`N
`
`Y
`
`
`
`products)
`
`S°““”“‘*“‘“‘R“°W “”0" -—-
`-—-
`
`OTC Labeling Review (for OTC
`products)
`
`Reviewer:
`
`N/A
`
`-—-
`
`antimicrobialproducts)
`
`-—-
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`10
`
`

`

`NDA# 202514
`Page 11 of 16
`
`
`Clinical Pharmacology
`
`
`Biostatistics
`
`
`Nonclinical
`(Pharmacology/Toxicology)
`
`Statistics (carcinogenicity)
`
`
`Immunogenicity (assay/assay
`validation) (for BLAs/BLA efficacy
`supplements)
`
`Product Quality (CMC)
`
`
`Quality Microbiology (for sterile
`products)
`
`CMC Labeling Review
`
`Facility Review/Inspection
`
`OSE/DMEPA (proprietary name)
`
`OSE/DRISK (REMS)
`
`OC/DCRMS (REMS)
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`
`Eric Yongheng Zhang
`
`Kim Bergman
`
`Yunfan Deng
`
`Yan Wang
`
`Jim Wild
`
`Wendy Schmidt
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`Maotang Zhou
`
`Linda L. Ng
`
`Jessica Cole
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`Denise Baugh
`
`
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`Y
`
`Y
`
`Y
`
`Y
`
`Y
`
`Y
`
`
`
`
`
`
`
`
`
`Y
`
`Y
`
`Y
`
`
`
`
`
`
`
`
`
`
`
`Y
`
`
`
`
`
`
`
`
`
`
`
`Version: 02/03/2011
`
`Reference ID: 2971625
`
`11
`
`

`

`NDA# 202514
`
`Page 12 of 16
`
`
`
`Bioresearch Monitoring (DSI)
`
`Reviewer: Kassa Ayalew
`
`
`
`- Tejashri Pulohit—Sheth -
`C°”"°”eds“bsm SWCSS) -—-
`-—-
`——-
`——-
`
`FILING MEETING DISCUSSION:
`
`GENERAL
`
`0
`
`505(b)(2) filing issues?
`
`X Not Applicable
`
`If yes, list issues:
`
`Per reviewers, are all parts in English or English
`translation?
`
`If no, explain:
`
`Electronic Submission comments
`
`List comments:
`
`
`
`I] Not Applicable
`X FILE
`
`[:1 REFUSE TO FILE
`
`El Review issues for 74-day letter
`
`0 Clinical study site(s) inspections(s) needed?
`
`If no, explain:
`
`0 Advisory Committee Meeting needed?
`
`Comments:
`
`Date if known:
`
`X NO
`E] To be determined
`
`Ifno, for an ony'nalm or BLA application, include the
`reason. For example:
`0
`this drug/biologic is not the first in its class
`0
`the clinical study design was acceptable
`
`this drngis not
`0 Reason:
`the first in its class
`
`Version: 02/03/201 1
`
`Reference ID: 2971625
`
`12
`
`

`

`NDA# 202514
`Page 13 of 16
`
`o the application did not raise significant safety
`or efficacy issues
`o the application did not raise significant public
`health questions on the role of the
`drug/biologic in the diagnosis, cure,
`mitigation, treatment or prevention of a
`disease
`
`
`• Abuse Liability/Potential
`
`
`
`Comments:
`
`•
`
`If the application is affected by the AIP, has the
`division made a recommendation regarding whether
`or not an exception to the AIP should be g