CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203168Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`
`

`

`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`****Pre-decisional Agency Information****
`
`Memorandum
`Date:
`March 20, 2013
`
`To:
`
`From:
`
`Subject:
`
`Mike Puglisi, Regulatory Health Project Manager
`Division of Transplant and Ophthalmology Products (DTOP)
`
`Christine Corser, Pharm.D., Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`
`OPDP Labeling Consult Review
`NDA #203168
`PROLENSATM (bromfenac ophthalmic solution) 0.07%
`
`As requested in your consult dated July 23, 2012, the Office of Prescription Drug
`Promotion (OPDP) has reviewed the draft labeling for PROLENSATM (bromfenac
`ophthalmic solution) 0.07%.
`
`Our comments are based on the substantially complete version of the labeling
`titled, “nda 203168 draft PI 3_20_13.doc” which was received via email from
`Mike Puglisi on March 20, 2013.
`
`OPDP has reviewed the PI and our comments are attached in the substantially
`complete clean version of the labeling.
`
`If you have any questions about our comments on the PI, please contact
`Christine Corser at 6-2653 or at christine.corser@fda.hhs.gov.
`
`Thank you for the opportunity to review this PI.
`
`Reference ID: 3279546
`
`4 Pages 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
`03/20/2013
`
`Reference ID: 3279546
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Label, Labeling and Packaging Review
`
`Date:
`
`February 8, 2013
`
`Reviewer:
`
`Jung Lee, RPh
`Division of Medication Error Prevention and Analysis
`Jamie Wilkins Parker, PharmD
`Team Leader:
`Division of Medication Error Prevention and Analysis
`
`Carol Holquist, RPh
`Division Director:
`Division of Medication Error Prevention and Analysis
`
`Prolensa (Bromfenac Ophthalmic Solution), 0.07%
`Drug Name and Strength:
`Application Type/Number: NDA 203168
`Applicant:
`Bausch & Lomb, Inc
`OSE RCM #:
`2012-2059
`*** This document contains proprietary and confidential information that should not be
`released to the public.***
`
`Reference ID: 3258577
`
`

`

`Contents
`
`1
`
`Introduction................................................................................................................. 1
`1.1
`Product Information ....................................................................................................... 1
`2 Methods and Materials Reviewed............................................................................... 2
`2.1
`Selection of Medication Error Cases.............................................................................. 2
`2.2
`Labels and Labeling....................................................................................................... 2
`3 Recommendations....................................................................................................... 3
`Appendices.......................................................................................................................... 5
`Appendix A. Database Descriptions............................................................................................ 5
`
`Reference ID: 3258577
`
`

`

`1
`
`INTRODUCTION
`
`This review evaluates the proposed container label, carton, and insert labeling for
`Prolensa (NDA 203168) for areas of vulnerability that could lead to medication errors.
`
`1.1
`
`BACKGROUND AND REGULATORY HISTORY
`
`On March 24, 2005, Xibrom (Bromfenac) ophthahnic solution 0.09% (NDA 021664) was
`approved for postoperative inflammation following cataract surgery with a twice-a—day
`dosing regimen. On May 25, 2010, the Applicant submitted a request for a Supplemental
`New Drug Application (sNDA) for a new proprietary name Bromday 03romfenac
`Sodium Hydrate) ophthahnic solution with a new strength, 0. 103 5% and a once-a-day
`dosing regimen.
`
`In a cover letter, also dated May 25, 2010, the Applicant stated their intent to discontinue
`marketing the existing product, Xibrom, in order to alleviate the confusion between
`proposed product Bromday and marketed product Xibrom. Xibrom was discontinued on
`May 24, 2011.
`
`On June 27, 2011, the Applicant submitted a request for a proprietary name review of the
`name Prolensa (Bromfenac Ophthahnic Solution) with a new strength, 0.07% and a
`similar once-a—day dosing regimen to Bromday under IND 060295. During the IND
`review, the Applicant stated they wanted a new proprietary name for the new formulation
`as it differs significantly from the Bromday formulation (Prolensa contains m4) less
`active ingredient, has a more neutral PH,
`m4) and contains tyloxapol
`mm); therefore, this product will have a dual
`proprietary name upon initial launch of the product.
`
`mm
`
`1.2
`
`PRODUCT INFORMATION
`
`The following product information is provided in the August 31, 2012 submission.
`
`0 Active Ingredient: Bromfenac
`
`0
`
`Indication of Use: Treatment of postoperative inflammation and reduction of
`ocular pain in patients who have undergone cataract extraction
`
`0 Route of Administration: Ophthahnic
`
`0 Dosage Form: Solution
`
`0
`
`Strength: 0.07%
`
`0 Dose and Frequency: One drop into the affected eye once daily beginning 1 day
`prior to surgery, continued on the day of surgery, and through the first 14 days of
`post-surgery
`
`0 How Supplied: 1.6 mL and 3 mL in a 7.5 mL container
`
`Reference ID: 3258577
`
`

`

`0
`
`Storage: Store at -15°C to 25°C (59°F to 77°F)
`
`0 Container and Closure System: White LDPE plastic squeeze bottle with a 15 mm
`mm dropper-tip and 15 mm
`M“) gray cap. The gray cap color is
`consistent with the American Academy of Ophthahnology’s policy statement
`“Color Code for Ocular Medications” which recommends the gray cap color for
`nonsteroidal anti—inflammatories (NSAIDS).
`
`2
`
`NIETHODS AND MATERIALS REVIEWED
`
`DMEPA searched the FDA FAERS database for bromfenac medication error reports.
`We also reviewed the Prolensa container labels, carton labeling, and package insert
`labeling submitted by the Applicant.
`
`2.1
`
`SELECTION OF MEDICATION ERROR CASES
`
`We searched the FDA Adverse Event Reporting System (FAERS) database using the
`strategy listed in Table 1 because Bromfenac ophthahnic solution is currently marketed
`under the name, Bromday and previous to that under the name Xibrom.
`
`Table l: FAERS Search Strate 1.;
`
`Date
`
`Dru N
`g
`
`ames
`
`MedDRA Search Strategy
`
`October 2, 2012
`
`Active Ingredient: Bromfenac
`'
`.
`Product Names: Xibrom, Bromda
`Medication Errors (HLGT)
`Product Packaging Issues I-ILT
`Product Label Issues HLT
`
`Product 0 1i
`
`Issues
`
`The FAERS database search identified 13 cases. Each case was reviewed for relevancy
`and duplication. After individual review, all 13 cases were excluded in the final analysis
`for the following reasons:
`
`0 Cases related to Duract (Bromfenac sodium capsules)
`
`0 Product quality issues related to generic Xibrom or complaints of burning
`eyes and itching from a different lot number of Bromday
`
`2.2
`
`LABELS AND LABELING
`
`Using the principles of human factors and Failure Mode and Effects Analysis,1 along
`with post marketing medication error data, the Division of Medication Error Prevention
`and Analysis (DMEPA) evaluated the following:
`
`0 Container Labels submitted August 21, 2012 (Appendix B)
`
`o Carton Labeling submitted August 21, 2012 (Appendix C)
`
`1 Institute for Healthcare Improvement (IHI). Failure Modes and Effects Analysis. Boston. IHI:2004.
`
`Reference ID: 3258577
`
`

`

`•
`
`Insert Labeling submitted August 21, 2012
`
`RECOMMENDATIONS
`3
`Based on this review, DMEPA recommends the following be implemented prior to
`approval of this NDA:
`
`3.1 COMMENTS TO THE DIVISION
`
`A.
`1.
`
`Insert Labeling
`In section 16 (How Supplied/Storage and Handling), include a space before
`the unit of measure. For example, “1.6mL in a 7.5mL container” should be
`revised to read as follows: 1.6 mL in a 7.5 mL container.
`2. The Applicant utilizes trailing zeros within the How Supplied/Storage and
`Handling section of the insert labeling. Trailing zeros may lead to 10-fold
`errors in dosing. DMEPA recommends removing all trailing zeros with the
`exception of when it is required to demonstrate the level of precision of the
`value being reported, such as for laboratory results, imaging studies that report
`size of lesions, or catheter/tube sizes.
`3. Add a unit of measure immediately following all numbers in the storage
`statement, as appropriate. For example, revise “15° – 25°C (59° -77°F)” to
`read as follows: 15°C to 25°C (59°F to 77°F).
`4.2 COMMENTS TO THE APPLICANT
`
`A. Container Label (0.6 mL Sample, 0.8 mL Sample, 1.6 mL Trade, 3 mL Trade
`Sizes)
`1. Revise the presentation of the proprietary name from all upper case letters
`“PROLENSA” to title case “Prolensa” to improve readability. Words set in
`title case form recognizable shapes, making them easier to read.
`2. Revise and relocate the statement “Once Daily” printed vertically on the left
`side of the principal display panel (PDP) to display horizontally below the
`strength statement to improve readability.
`3. Remove the word “Sterile”.
`4. Debold and relocate the net quantity statement away from the strength
`statement so it does not have greater prominence than that of the strength
`statement and the established name.
`5. Remove the trailing zero from the 3.0 mL trade size label and revise to read
`“3 mL”.
`
`B.
`
`Carton Labeling (0.6 mL Sample, 0.8 mL Sample, 1.6 mL Trade, 3 mL Trade
`Sizes)
`1. See comments A1and A5.
`
`Reference ID: 3258577
`
`3
`
`

`

`2. Relocate the route of administration statement, “For topical application in the
`eye” to the PDP directly below the dosage form and strength statements.
`3. Debold the net quantity statement so it does not have greater prominence than
`that of the strength statement and the established name.
`If you have further questions or need clarifications, please contact Karen Townsend,
`project manager, at 301-796-5413.
`
`Reference ID: 3258577
`
`4
`
`

`

`APPENDICES
`
`APPENDIX A. DATABASE DESCRIPTIONS
`Adverse Event Reporting System (AERS)
`The Adverse Event Reporting System (AERS) is a computerized information database designed
`to support the FDA's post-marketing safety surveillance program for drug and therapeutic
`biologic products. The FDA uses AERS to monitor adverse events and medication errors that
`might occur with these marketed products. The structure of AERS complies with the international
`safety reporting guidance (ICH E2B) issued by the International Conference on Harmonisation.
`Adverse events in AERS are coded to terms in the Medical Dictionary for Regulatory Activities
`terminology (MedDRA).
`
`AERS data do have limitations. First, there is no certainty that the reported event was
`actually due to the product. FDA does not require that a causal relationship between a
`product and event be proven, and reports do not always contain enough detail to properly
`evaluate an event. Further, FDA does not receive all adverse event reports that occur with
`a product. Many factors can influence whether or not an event will be reported, such as
`the time a product has been marketed and publicity about an event. Therefore, AERS
`cannot be used to calculate the incidence of an adverse event in the U.S. population.
`
`Appendix B: Container Labels
`
`Professional Sample Bottle Label for 0.6 mL Fill Size:
`
`Reference ID: 3258577
`
`5
`
`(b) (4)
`
`4 Page(s) has 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/
`----------------------------------------------------
`JUNG E LEE
`02/08/2013
`
`JAMIE C WILKINS PARKER
`02/08/2013
`
`CAROL A HOLQUIST
`02/08/2013
`
`Reference ID: 3258577
`
`

`

`M E M O R A N D U M DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`PUBLIC HEALTH SERVICE
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`____________________________________________________________________________
`
`CLINICAL INSPECTION SUMMARY
`
`February 4, 2013
`
`Michael Puglisi, Project Manager
`William M. Boyd, Medical Team leader
`Division of Transplant and Ophthalmology Products
`
`Kassa Ayalew, Medical Officer
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Susan Leibenhaut
`Acting Team Leader
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Susan Thompson
`Acting Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigators
`
`Evaluation of Clinical Inspections
`
`203168
`
`DATE:
`
`TO:
`
`
`
`FROM:
`
`
`
`
`
`
`
`THROUGH:
`
`SUBJECT:
`
`NDA:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`APPLICANT:
`
`ISTA Pharmaceuticals, Inc.
`
`DRUG:
`
`ProlensaTM (bromfenac ophthalmic solution 0.7%)
`
`
`
`NME:
`
`
`
`No
`
`INDICATION: Treatment of postoperative inflammation and reduction of ocular pain
`patients who have undergone cataract extraction
`
`
`
`Reference ID: 3255045
`
`

`

`Page 2 Clinical Inspection Summary: NDA: 203168
` Prolensa™ (bromfenac ophthalmic solution 0.7%)
`
`THERAPEUTIC CLASSIFICATION:
`
`CONSULTATION REQUEST DATE:
`
`
`
`
`
`Standard
`
`July 23, 2012
`
`INSPECTION SUMMARY GOAL DATE:
`
`February 7, 2013
`
`ACTION GOAL DATE:
`
`PDUFA DATE:
`
`
`I. BACKGROUND:
`
`
`
`
`
`
`
`
`
`March 7, 2013
`
`April 7, 2013
`
`
`
`The Applicant, ISTA Pharmaceuticals, Inc. (ISTA) submitted an original New Drug
`Application (NDA) for ProlensaTM (bromfenac ophthalmic solution) 0.07% to support an
`indication for the treatment of inflammation and pain associated with cataract extraction.
`Bromfenac ophthalmic solution 0.07% is a new formulation with lower concentration of
`bromfenac and planned to be administered as once daily (QD).
`
`The Office of Scientific Investigation received a consult from Division of Transplant and
`Ophthalmology Products to conduct clinical inspections of the following two identical studies:
`
`S00124-ER (East Region) entitled “Efficacy and Safety of Bromfenac Ophthalmic
`Solution vs. Placebo for the Treatment of Ocular Inflammation and Pain Associated
`with Cataract Surgery”
`
`S00124-WR (West Region) entitled “Efficacy and Safety of Bromfenac Ophthalmic
`Solution vs. Placebo for the Treatment of Ocular Inflammation and Pain Associated
`with Cataract Surgery”.
`
`The studies were multi-center, randomized, double-masked, parallel-group, and placebo-
`controlled studies to evaluate the efficacy of bromfenac for the treatment of ocular
`inflammation and pain associated with cataract surgery with PCIOL (posterior chamber
`intraocular lens). For both studies, subjects were to be randomized to receive either bromfenac
`or placebo in a ratio of 1:1. The primary endpoint of efficacy was the proportion of subjects
`who had cleared ocular inflammation by Day 15. Approximately 220 subjects were to be
`randomized to receive either bromfenac or placebo in a ratio of 1:1 in each study (Study
`S00124-WR and Study S00124-ER ).
`
`One site from each study was chosen for inspection based on enrollment, number of INDs in
`the OSI database, and previous inspectional history.
`
`Reference ID: 3255045
`
`

`

`Page 3 Clinical Inspection Summary: NDA: 203168
` Prolensa™ (bromfenac ophthalmic solution 0.7%)
`
`II. RESULTS (by Site):
`
`Name of CI
`
`Protocol # /Site #/ # of
`Subjects Enrolled:
`
`Inspection
`Date
`
`Classification
`
`S00124-ER
`Site #58
`21 subjects
`
`S00124-WR
`Site #23
`22 subjects
`
`Leonard Cacioppo, MD
`Hernando Eye Institute
`14543 Cortez Boulevard
`Brooksville, FL 34613
`Damien Goldberg, MD
`Wolstan & Goldberg Eye Associates
`23600 Telo Ave, Suite 100
`Torrance, CA 90505
`Key to Classifications
`NAI = No deviation from regulations.
`VAI = Deviation(s) from regulations.
`OAI = Significant deviations from regulations. Data unreliable.
`Pending = Preliminary classification based on information in 483 or preliminary communication with the field;
`EIR has not been received from the field and complete review of EIR is pending.
`
`NAI
`
`VAI
`
`September
`10 to 14,
`2012
`
`August 24 to
`September 6,
`2012
`
`1. Leonard Cacioppo, MD
`Hernando Eye Institute
`14543 Cortez Boulevard, Brooksville, FL 34613
`
`a. What was inspected: This inspection was performed a data audit for Protocol #
`S00124-ER. There are
` associated with the inspected entity in CDER’s
`database, and the CI had one prior inspection in November, 2003 that was classified
`NAI.
`
`At this site, a total of 22 study subjects were screened for Protocol # S00124-ER.
`Twenty one (21) subjects were enrolled, randomized, and completed the study. Of
`the twenty one (21) subjects who completed Visit Seven (Day 22+3 or 7 + 3 Days
`after last dose of investigational product, ten (10) subjects discontinued
`investigational product prior to visit 7. Eight (8) of the 10 subjects who
`discontinued were in the placebo arm and two were on the investigational product
`arm. The source documents revealed that the above subjects were discontinued
`secondary to lack of efficacy and were placed on rescue medication.
`
`An in depth audit of the study records for all 22 subjects was conducted. There were
`no limitations to the inspection. Records reviewed included, but were not limited
`to, source documents, protocol specified blinding/randomization procedures,
`inclusion/exclusion criteria, adverse events, primary efficacy endpoints, protocol
`deviations, concomitant therapies, and test article accountability. In addition, IRB
`correspondence, monitoring logs and correspondence, and financial disclosure
`documentation were reviewed.
`
`Reference ID: 3255045
`
`(b) (4)
`
`

`

`Page 4 Clinical Inspection Summary: NDA: 203168
` Prolensa™ (bromfenac ophthalmic solution 0.7%)
`
`b. General observations/commentary: The investigator’s source documents were
`organized, complete and legible. The primary endpoint data were verifiable. There
`were two instances of unreported adverse events (AE). Those adverse events were
`non-ocular episode of syncope, ecchymosis of left upper eyelid (Subject 5812) and
`floater in the left study eye (Subject 5807). The above adverse events were reported
`as not serious and not related. They were considered isolated instances. No
`significant regulatory violations were noted and no Form FDA 483 was issued. The
`study appears to have been executed appropriately at this site.
`
`c. Assessment of data integrity: Based on inspectional findings and the observations
`noted, efficacy and safety data obtained from this site are considered reliable.
`
`2. Damien Goldberg, MD
`Wolstan & Goldberg Eye Associates
`23600 Telo Ave, Suite 100, Torrance, CA 90505
`
`a. What was inspected: This inspection was conducted in accordance with Compliance
`Program 7348.811. There were
` associated with the inspected entity in CDER’s
`database, and the CI had no prior inspection.
`
`This inspection was performed as a data audit for Protocol S00124-WR. At this site, 22
`subjects were screened. Twenty two (22) subjects were enrolled and randomized into the
`study. A total of 20 subjects completed the study. An audit of 22 subjects’ records was
`conducted. There was no evidence of under reporting of adverse events. The primary
`efficacy endpoint data was verifiable.
`
`The inspection included reviews of the following items: 1) entry criteria, 2) diagnosis of
`target disease, 3) efficacy variables, and 4) adequacy of adverse experience reporting. In
`addition, drug accountability records, Informed Consents Documents, IRB approval and
`dates, and sponsor monitoring records were reviewed. All primary efficacy endpoint data
`were compared with the sponsor supplied line listings and no discrepancies were noted.
`There were no limitations to the inspection.
`
`b. General observations/commentary: In general, the study was conducted
`appropriately. However, a Form FDA 483, Inspectional Observations, was issued for
`failure to conduct the study in accordance with the signed statement of investigator and
`investigational plan [21 CFR 312.60]. Specifically,
`
`1. Failure to exclude Subject # 2309 (bromfenac arm) who had eye pain that was
`rated as mild on the Ocular Comfort Grading at the time of Screening.
`
`OSI Reviewer Comments: The clinical investigator should have excluded the
`above subject from participation in this study based on the Exclusion Criterion
`requiring that subjects have no ocular pain. Dr. Goldberg’s written response
`
`Reference ID: 3255045
`
`(b) (4)
`
`

`

`Page 5 Clinical Inspection Summary: NDA: 203168
` Prolensa™ (bromfenac ophthalmic solution 0.7%)
`
`(dated September 20, 2012) to the Form FDA 483, acknowledges the findings
`identified above and stated that he has implemented corrective actions. The
`above-mentioned protocol deviation was identified and described by the study
`monitor and is noted in the data listings submitted by the sponsor. This finding
`was isolated in nature, and it is unlikely that it would affect subject safety or
`data reliability.
`
`2. Failure to exclude Subject # 2322 (placebo arm) who received prior/ ongoing
`concomitant medications (tamsulosin and finasteride) from the study.
`
`OSI Reviewer Comments: The clinical investigator should have excluded the
`above subject from participation in this study based on Exclusion Criterion
`listing the above medications as exclusionary. This protocol deviation was
`identified and described by the study monitor and is noted in the data listings
`submitted by the sponsor. The CI reported the deviations for Subject # 2322 to
`the sponsor. In his written response, he acknowledged that he incorrectly
`included this patient in the study. He plans to correct the problem in the future
`prior to considering patients for clinical trials. This finding was isolated in
`nature, and it is unlikely that it would affect subject safety or data reliability.
`
`Dr. Goldberg adequately responded to the inspectional findings in a letter dated
`September 20, 2012. His response to the FDA Form 483 adequately addresses and
`explains findings that were initially considered violations by the field investigator in
`three additional subjects. The three subjects were Subject # 2310 (bromfenac arm) who
`was suspected to have received artificial tears, Subject # 2301 (placebo arm) suspected
`to have received heparin and tamsulosin, and Subject # 2312 (bromfenac arm)
`suspected to have had history of hypersensitivity to salicylates.
`
`c. Assessment of data integrity: Although regulatory violations were noted above, it is
`unlikely, based on the isolated nature of the violations, that they significantly affect overall
`reliability of safety and efficacy data from the site. The data derived from Dr. Goldberg’s
`site are considered reliable.
`
`III. OVERALL ASSESSMENT OF FINDINGS AND RECOMMENDATIONS
`
`Two clinical investigator sites were inspected for this application. The data derived from both
`inspected sites are considered reliable. The classification of the Clinical Investigator inspection
`of Dr. Cacioppo is No Official Action Indicated (NAI). The classification of the Clinical
`Investigator inspection of Dr. Goldberg is Voluntary Action Indicated (VAI).
`
`Reference ID: 3255045
`
`

`

`Page 6 Clinical Inspection Summary: NDA: 203168
` Prolensa™ (bromfenac ophthalmic solution 0.7%)
`
`{See appended electronic signature page}
`
`Kassa Ayalew, M.D.
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`CONCURRENCE:
`
`
`
`
`
`
`
`
`
` {See appended electronic signature page}
`
`Susan Thompson, M.D.
`Acting Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Reference ID: 3255045
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`KASSA AYALEW
`02/04/2013
`
`SUSAN D THOMPSON
`02/04/2013
`
`Reference ID: 3255045
`
`

`

`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]
`
`NDA # 203168
`BLA#
`
`NDA Supplement #:S-
`BLA Su. :lement #
`
`Efficacy Supplement Type SE-
`
`A lication Information
`
`Proprietary Name: Prolensa
`Established/Proper Name: bromfenac
`Dosage Form: ophthalmic solution
`Stren ths: 0.07%
`
`Applicant: ISTA Pharmaceuticals, Inc.
`A cut for A .licant (if a t licable):
`Date of Application: June 6, 2012
`Date of Receipt: June 7. 2012
`Date clock started afier UN:
`
`PDUFA Goal Date: A ril 7. 2013
`Filinv Date: Aufi
`t6. 2012
`
`Action Goal Date (if different):
`Date ofFilin Meetin: Jul 24, 2012
`
`Chemical Classification: 1.2.3 etc. ori
`' Ial NDAs on]
`T pe-S
`Proposed indication: treatment of inflammation and pain associated with cataract extraction
`
`Type of Original NDA:
`AND (if applicable)
`Type ofNDA Supplement:
`
`If505(b)(2): Drafl the “505(b)(2) Assessment” reviewfound at:
`I:
`://inside. do. ov:9003/CDER/0 ceo 'ewDru s/Immediateo ce/L'CM02 7499
`and re er to A endix A or urther in ormation.
`
`Review Classification:
`
`Ifthe application includes a complete response to pediatric WR, review
`classification is Priority.
`
`K4 505(b)(l)
`I 505 u 2
`I] 505(b)(l)
`E] 505(b)(2)
`
`D Priority
`
`
`
`E] Tropical Disease Priority
`Review Voucher submitted
`Ifa tropical diseasepriority review voucher was submitted, review
`classification is Priority.
`
`
`Resubmission afier withdrawal? E]
`Part 3 Combination Product? I
`
`Resubmission after refuse to file? El
`I Convenience kit/Co-package
`E] Pre-filled drug delivery device/system (syringe, patch. etc.)
`E] Pre-filled biologic delivery device/system (syringe, patch, etc.)
`Ifyt’s, can!!!“ ”I? 0177“ 0f
`Cowbim’io" ”MW" (00’) and “RV E] Device coated/unpregnated/combined with drug
`”m" 0" “I, 1""’'Cm’” “"5",“
`E] Device coated/unpregnated/combined with biologic
`E] Separate products requiring cross-labeling
`E] Drug/Biologic
`E] Possible combination based on cross-labeling of separate
`products
`C] Other (dru . device/biolo l'cal roduct)
`
`Version: 6/26/12
`
`Reference ID: 31 76962
`
`1
`
`

`

`
`
`E] Fast Track
`El Rolling Review
`E] Orphan Designation
`
`E] Rx-to-OTC switch. Full
`E] Rx—to-OTC switch, Partial
`[:1 Direct-to-OTC
`
`Other:
`
`E] PMC response
`E] PMR response:
`El FDAAA [505(0)]
`El PREA deferred pediatric studies [21 CFR
`314.55(b)/21CFR 601.27(b)]
`El Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
`El Animal rule postmarketing 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): IND 60295
`
`Goal Dates/Product Names/Classification Pro - rties
`
`PDUFA and Action Goal dates correct in tracking system?
`
`Ifno, ask the document room staffto correct them immediately.
`These are the dates used or calculating ins
`
`Are the proprietary. established/proper. and applicant names
`correct in tracking system?
`
`Ifno, ask the document room staffto make the corrections. Also,
`ask the document room stafl'to add the establishedérroper 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 New Application and New Supplement Notification Checklists
`for a list ofall classifications/properties at:
`h
`://inside. da. ov:9003/CDER/0 Iceo
`usinessProcessSu ort/ucml 63969.11!
`
`2 I
`
`fno, ask the document room staffto make the appropriate
`entries.
`
`A :lication Int_ ' Poli
`
`\/
`
`
`
`Is the application afi‘ected by the Application Integrity Policy
`(AIP)? Check theAIPlist at:
`://wu'w. (Ia. ov/ICECI/En orcementActions/4
`
`licationInte ri 'Poli
`
`‘/de an]!
`
`m...
`
`I..—
`
`If affected by AIP, has OC/OMPQ been notified of the
`submission? If yes, date notified:
`—EEIID—
`Is Form 3397 (User Fee Cover Sheet) included with
`authorized signature?
`
`\]
`
`Version: 6/26/12
`
`Reference ID: 31 76962
`
`2
`
`

`

`
`
`User Fee Status
`
`Payment for this application:
`
`Ifa userfee is required and it has not been paid (and it E Paid
`is not exempted or waived), the application is
`E] Exempt (orphan. government)
`unacceptableforfilingfollowing a 5-day graceperiod.
`'3 Waived (e.g.. small business, public health)
`Review stops. Send Unacceptablefor Filing (UN) letter B Not required
`and contact userfee stafl.‘
`
`Payment of other user fees:
`
`E Not in arrears
`Ifthefirm is in arrearsfor otherfees (regardless of
`whether a userfee has been paidfor this application), D In arrears
`the application is unacceptableforfiling (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the user ee stai .
`
`IAs/NDA Eflica
`
`mill—
`Is the application for a duplicate of a listed drug and eligible—III-
`
`SuI Ilements oI
`
`3
`
`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 I
`
`Is the application for a duplicate of a listed drug whose only
`difference 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 505(b (2 review staj in the Immediate 0) ice 0 New
`_‘
`Is there unexpired exclusivity on the active moiety (e.g.. 5-
`year. 3-year. orphan. or pediatric exclusivity)?
`Check the Electronic Orange Book at:
`haM/www. accessdata. (do. gov/scrigts/cder/ob/detauIt. ctm
`
`If cs. Ilease list below:
`
`Application No.
`
`Exclusivity Code
`
`Exclusivity Expiration
`
`Ifthere is unavpired, 5-year m’clusivitv remaining on the active moietvfor the proposed drugproduct, a 505(b)(2)
`application cannot be submitted until the period ofexclusivitv expires (unless the applicantprovides paragraph IV
`patent certification; then an application can be submittedfour years afier the date ofapproval.) Pediatric
`exclusivity will extend both ofthe timefi'ames in this provision by 6 months. 21 CF