CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`206276Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`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
`
`DATE:
`
`TO:
`
`FROM:
`
`THROUGH:
`
`CLINICAL INSPECTION SUMMARY
`January 2, 2015
`
`Lois Almoza, Regulatory Project Manager
`Wiley Chambers, M.D., Deputy Division Director
`William Boyd, M.D., Medical Team Leader
`Division of Topical and Ophthalmic Products
`
`Roy Blay, Ph.D.
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Janice Pohlman, M.D., M.P.H
`Team Leader
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`Kassa Ayalew, M.D., M.P.H.
`Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`SUBJECT:
`
`Evaluation of Clinical Inspections
`
`NDA:
`
`206276
`
`APPLICANT:
`
`Alcon Research, Ltd.
`
`DRUG:
`
`NME:
`
`Olopatadine ophthalmic solution, 0.7%
`
`No
`
`THERAPEUTIC
`CLASSIFICATION: Priority Review
`
`INDICATION:
`
`Treatment of ocular itching
`
`
`
`Reference ID: 3683437
`
`

`

`Page 2- NDA 206276 – Olopatadine ophthalmic solution, 0.7% – Clinical Inspection Summary
`
`CONSULTATION REQUEST DATE:
`CLINICAL INSPECTION SUMMARY DATE:
`DIVISION ACTION GOAL DATE:
`PDUFA DATE:
`
`September 9, 2014
`January 9, 2015
`January 30, 2015
`January 30, 2015
`
`I. BACKGROUND:
`
`The Applicant submitted this NDA to support the use of olopatadine ophthalmic solution,
`0.7%, for the treatment of ocular itching.
`
`The pivotal studies, C-10-126 entitled, “A Multicenter, Randomized, Double-Masked,
`Vehicle and Active Controlled, Parallel-Group Efficacy and Safety Study of AL-4943A
`Ophthalmic Solution, 0.77% in Patients with Allergic Conjunctivitis Using the Conjunctival
`Allergen Challenge (CAC) Model”, and C-12-028 entitled “A Multicenter, Randomized,
`Double-Masked, Vehicle-Controlled, Parallel-Group Study Evaluating the Safety of
`AL-4943A Ophthalmic Solution 0.77% Administered Once Daily”, were inspected in
`support of this application.
`
`Drs. Torkildsen’s and Rand’s clinical sites were selected for inspection because of high
`subject enrollments and previous inspection histories.
`
`II. RESULTS (by Site):
`
`Name of CI, Location
`
`Gail Torkildsen, M.D.
`Andover Eye Associates
`138 Haverhill Street
`Andover, MA 01810
`Allison Rand, M.D.
`Rand Eye Institute
`5 Sample Road
`Deerfield, FL 33064
`
`Protocol #/
`Site #/
`# of Subjects (enrolled)
`C-10-126/
`3505/
`97
`
`Inspection Dates
`
`Final
`Classification
`
`21-24 Oct 2014
`
`NAI
`
`C-12-028/
`6448/
`40
`
`Nov 2014
`
`Pending,
`preliminary
`classification NAI
`
`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 Form FDA 483 or preliminary communication
`with the field; EIR has not been received from the field or complete review of EIR is pending.
`
`Reference ID: 3683437
`
`

`

`Page 3- NDA 206276 – Olopatadine ophthalmic solution, 0.7% – Clinical Inspection Summary
`
`1. Gail Torkildsen, M.D.
`Andover Eye Associates
`138 Haverhill Street
`Andover, MA 01810
`
`a. What was inspected: At this site for Protocol C-10-126, 163 subjects were screened,
`97 subjects were enrolled, and 94 subjects completed the study.
`
`The records for all subjects were reviewed which included but were not limited to
`informed consent forms for all screened subjects, financial disclosure forms, protocol
`adherence, subject eligibility, randomization, IRB communications, concomitant
`medications, adverse event reporting, and test article accountability and storage.
`Source data was compared with electronic case report forms (eCRFs) and verified
`against line listings.
`
`b. General observations/commentary: A Form FDA 483 was not issued at the
`conclusion of the inspection. Review of the records noted above revealed no
`significant discrepancies or regulatory violations.
`
`c. Assessment of data integrity: The study appears to have been conducted adequately,
`and the data generated by this site appear acceptable in support of the respective
`indication.
`
`2. Allison Rand, M.D.
`Rand Eye Institute
`5 Sample Road
`Deerfield, FL 33064
`
`a. What was inspected: At this site for Protocol C-12-028, 41 subjects were screened,
`40 subjects were enrolled in the study, and all 40 subjects completed the study.
`
`Informed consent forms were reviewed for all 41 screened subjects. Study data were
`validated for all 41 sets of records and the records of 20 subjects were reviewed for
`protocol compliance.
`
`b. General observations/commentary: A Form FDA 483 was not issued at the
`conclusion of the inspection Review of the records noted above revealed no
`significant discrepancies or regulatory violations.
`
`c. Assessment of data integrity: The study appears to have been conducted adequately,
`and the data generated by this site appear acceptable in support of the respective
`indication.
`
`Reference ID: 3683437
`
`

`

`Page 4- NDA 206276 – Olopatadine ophthalmic solution, 0.7% – Clinical Inspection Summary
`
`III.OVERALL ASSESSMENT OF FINDINGS AND RECOMMENDATIONS
`
`The clinical sites of Drs. Torkildsen and Rand were inspected in support of this NDA.
`Neither Dr. Torkildsen nor Dr. Rand was issued a Form FDA 483, and these inspections were
`classified No Action Indicated (NAI). The data generated by these clinical sites appear
`adequate in support of the respective indication.
`
`NOTE: The final Establishment Inspection Report (EIR) for Dr. Rand’s site has not been
`received by OSI. Should the classification of this inspection change upon review of the EIR,
`an inspection summary addendum will be issued to DTOP.
`
`{See appended electronic signature page}
`
`Roy Blay, Ph.D.
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`CONCURRENCE:
`
`{See appended electronic signature page}
`
`Janice Pohlman, M.D., M.P.H.
`Team Leader
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigations
`
`{See appended electronic signature page}
`
`Kassa Ayalew, M.D., M.P.H.
`Acting Branch Chief
`Good Clinical Practice Assessment Branch
`Division of Good Clinical Practice Compliance
`Office of Scientific Investigation
`
`Reference ID: 3683437
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROY A BLAY
`01/07/2015
`
`JANICE K POHLMAN
`01/07/2015
`
`KASSA AYALEW
`01/07/2015
`
`Reference ID: 3683437
`
`

`

`Lois Almoza, Regulatory Health Project Manager
`Division of Transplant and Ophthalmology Products (DTOP)
`
`Christine Corser, PharmD, RAC, Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`
`FOOD AND DRUG ADMINISTRATION
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`****Pre-decisional Agency Information****
`
`
`
`
`
`Memorandum
`
`Date:
`January 6, 2015
`
`
`To:
`
`
`
`
`From:
`
`
`
`Subject:
`
`
`
`
`
`
`As requested in DTOP’s consult dated October 6, 2014, OPDP has reviewed the
`draft PI and proposed carton and container labeling for Pazeo.
`
`OPDP reviewed the proposed substantially complete version of the PI titled,
`“Wiley’s Edited Labeling.doc” received via the DTOP SharePoint website on
`January 5, 2015. OPDP’s comments are provided in the attached clean version
`of the substantially complete labeling.
`
`OPDP has also reviewed the following proposed carton and container labeling:
`•
`“draft-carton-container-labels-0pt5carton.pdf”
`•
`“draft-carton-container-labels-0pt5label.pdf”
`•
`“draft-carton-container-labels-0pt5pouch.pdf”
`•
`“draft-carton-container-labels-2pt5carton.pdf”
`•
`“draft-carton-container-labels-2pt5label.pdf”
`
`Olopatadine hydrochloride ophthalmic solution 0.7%
`NDA #2062 76
`
`
`These were accessed on the DTOP SharePoint website on January 5, 2015.
`OPDP notes that the proposed carton and container labeling present a 0.77%
`percent, while the substantially complete PI refers to the product containing 0.7%
`of olopatadine. OPDP reminds DTOP to revise the carton and container labeling
`to be consistent with the PI. OPDP has no further comments on the proposed
`carton and container labeling.
`
`Thank you for the opportunity to review and provide comments on this proposed
`labeling. If you have any questions please contact Christine Corser at 6-2653 or
`Christine.Corser@fda.hhs.gov.
`
`
`
`Reference ID: 3682957
`
`9 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`(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/
`----------------------------------------------------
`
`CHRISTINE G CORSER
`01/06/2015
`
`Reference ID: 3682957
`
`

`

`LABEL AND LABELING REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the public***
`
`Date of This Review:
`November 19, 2014
`Requesting Office or Division:
`Division of Transplant and Ophthalmology Products (DTOP)
`Application Type and Number: NDA 206276
`Product Name and Strength:
`Olopatadine Hydrochloride Ophthalmic Solution, 0.77%
`Product Type:
`Single Ingredient
`Rx or OTC:
`Rx
`Applicant/Sponsor Name:
`Alcon
`Submission Date:
`July 30, 2014
`OSE RCM #:
`2014-1737
`DMEPA Primary Reviewer:
`Rachna Kapoor, PharmD
`DMEPA Team Leader:
`Yelena Maslov, PharmD
`
`Reference ID: 3660746
`
`1
`
`

`

`1
`
`REASON FOR REVIEW
`
`This review evaluates the proposed container closure system, container label, carton labeling,
`pouch labeling, and prescriber information labeling for Olopatadine Hydrochloride Ophthalmic
`Solution, NDA 206276, for areas of vulnerability that could lead to medication errors.
`
`2 MATERIALS REVIEWED
`We considered the materials listed in Table 1 for this review. The Appendices provide the
`methods and results for each material reviewed.
`
`Table 1. Materials Considered for this Label and Labeling Review
`Material Reviewed
`Appendix Section (for Methods
`and Results)
`A
`B
`C
`D (N/A)
`E
`F (N/A)
`G
`
`Product Information/Prescribing Information
`FDA Adverse Event Reporting System (FAERS)
`Previous DMEPA Reviews
`Human Factors Study
`ISMP Newsletters
`Other
`Labels and Labeling
`N/A=not applicable for this review
`
`OVERALL ASSESSMENT OF THE MATERIALS REVIEWED
`3
`DMEPA identified that the container labels, carton labeling, and pouch labeling can be
`improved from a safety perspective by increasing the prominence of the route of
`administration on the container labels and deleting the line under Tradename to follow the
`Code of Federal Regulations for intervening graphic matter. We provide recommendations
`below in Section 4.1.
`
`FAERS and ISMP search did not identify any relevant information to inform this review.
`
`4
`
`CONCLUSION & RECOMMENDATIONS
`
`DMEPA concludes that the prescriber information labeling is acceptable. We have no
`additional comments for the prescriber information labeling at this time.
`
`Reference ID: 3660746
`
`2
`
`

`

`Additionally, DMEPA concludes that the proposed container label, carton labeling and pouch
`labeling can be improved to increase the prominence and readability of important information
`on the label to promote the safe use of the product.
`
`Based on this review, DMEPA recommends the following be implemented prior to the approval
`of this NDA:
`
`4.1
`
`RECOMMENDATIONS FOR ALCON
`
`A.
`
`Container Label (trade size and professional sample)
`i. Delete
` Tradename as this is considered intervening graphic matter
`with the proprietary name. As per 21 CFR 201.10 (a), the proprietary name shall
`appear without any intervening graphic matter
`
`ii. We recommend adding the statement “For Topical Ophthalmic Use Only” to
`highlight the correct route of administration. We recommend this revision to
`help prevent wrong route of administration errors. This can be achieved by
`decreasing the prominence of the manufacturer name by decreasing the font
`size or moving to the side panel.
`
`B.
`
`Carton Labeling (trade size and professional sample)
`
`i.
`ii.
`
`iii.
`
`
`
`See A. i. and revise carton labeling accordingly.
`Increase the color contrast between the established name and the background
`of the label as it is hard to read the white text of established name on the
`background. As per the Draft Guidance: Safety Considerations for Container
`Labels and Carton Labeling Design to Minimize Medication Errors1, the color
`contrast between the text and the container label background color should be
`chosen to afford adequate legibility of the text.
`Decrease the prominence of the manufacturer name by decreasing the font size
`and deleting the green box around it as per the Draft Guidance: Safety
`Considerations for Container Labels and Carton Labeling Design to Minimize
`Medication Errors1. The company name appears prominent since it is bolded
`and surrounded by the green box and thus, takes attention away from more
`important information on the labeling such as product’s established name and
`strength.
`
`1 2013 Draft Guidance: Safety Considerations for Container Labels and Carton Labeling Design to Minimize
`Medication Errors
`http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm349009.pdf
`
`Reference ID: 3660746
`
`3
`
`(b) (4)
`
`(b) (4)
`
`

`

`iv.
`
`Ensure that all the panels on the carton labeling contain the proprietary name,
`established name, dosage form, and strength for ease of identification of the
`product.
`
`C.
`
`Carton Labeling (trade size)
`
`i.
`
`i.
`
`D.
`
`Add the statement “Shake well before use” to the principal display panel as this
`statement provides important information regarding the correct use of the
`product.
`
`Carton Labeling (professional sample)
`
`” to the principal display panel as
`Relocate the statement “
`this statement provides important information regarding the correct use of the
`product.
`
`E.
`
`Pouch Labeling
`
`i.
`
`See A. i., A. ii., B. iii., and C. i. and revise pouch labeling accordingly.
`
`Reference ID: 3660746
`
`4
`
`(b) (4)
`
`

`

`APPENDICES: METHODS & RESULTS FOR EACH MATERIALS REVIEWED
`
`APPENDIX A. PRODUCT INFORMATION/PRESCRIBING INFORMATION
`Table 2 presents relevant product information for Olopatadine Hydrochloride that Alcon
`submitted on July 30, 2014.
`
`Table 2. Relevant Product Information for Olopatadine Hydrochloride
`Initial Approval Date
`N/A
`Active Ingredient
`Olopatadine hydrochloride
`Indication
`The treatment of ocular itching associated with allergic
`conjunctivitis
`Ophthalmic
`Ophthalmic solution
`0.77%
`Instill one drop in each affected eye once daily
`2.5 mL fill in a 4 mL oval bottle
`Store at 2o – 25oC (36o – 77oF)
`
`Route of Administration
`Dosage Form
`Strength
`Dose and Frequency
`How Supplied
`Storage
`
`Reference ID: 3660746
`
`5
`
`

`

`APPENDIX B. FDA ADVERSE EVENT REPORTING SYSTEM (FAERS)
`B.1 Methods
`We searched the FDA Adverse Event Reporting System (FAERS) on November 10, 2014 using
`the criteria in Table 3, and then individually reviewed each case. We limited our analysis to
`cases that described errors possibly associated with the label and labeling. We used the NCC
`MERP Taxonomy of Medication Errors to code the type and factors contributing to the errors
`when sufficient information was provided by the reporter2
`
`Table 3: FAERS Search Strategy
`Date Range
`Product
`
`Event (MedDRA Terms)
`
`No date range
`Olopatadine [active ingredient]
`Olopatadine hydrochloride [active ingredient]
`Medication Errors [HLGT]
`Product Packaging Issues [HLT]
`Product Label Issues [HLT]
`Product Quality Issues (NEC)[HLT]
`
`Results
`B.2
`Our search from Table 3 identified 9 cases. After individual review, 9 cases were excluded from
`the final analysis for the following reasons:
` Foreign case (n=1)
` Product quality issue (n=1)
` Concomitant medication (n=3)
` Adverse event not related to a medication error (n=1)
` Cases involving Patanase Nasal Spray (not relevant to this review) (n=2)
` Medication error (not relevant to this review) (n=1)
`o A prescription for Patanol drops written for a patient was filled in the name of
`the patient’s spouse
`
`List of FAERS Case Numbers
`B.3
`Below is a list of the FAERS case number and manufacturer control numbers for the cases
`relevant for this review.
`
`
`2 The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Taxonomy of
`Medication Errors. Website http://www.nccmerp.org/pdf/taxo2001-07-31.pdf.
`
`6
`
`Reference ID: 3660746
`
`

`

`Description of FAERS
`B.4
`The FDA Adverse Event Reporting System (FAERS) is a database that contains information on
`adverse event and medication error reports submitted to FDA. The database is designed to
`support the FDA's postmarket safety surveillance program for drug and therapeutic biologic
`products. The informatic structure of the FAERS database adheres to the international safety
`reporting guidance issued by the International Conference on Harmonisation. FDA’s Office of
`Surveillance and Epidemiology codes adverse events and medication errors to terms in the
`Medical Dictionary for Regulatory Activities (MedDRA) terminology. Product names are coded
`using the FAERS Product Dictionary. More information about FAERS can be found at:
`http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseD
`rugEffects/default.htm.
`
`Reference ID: 3660746
`
`7
`
`

`

`APPENDIX C. PREVIOUS DMEPA REVIEWS
`C.1 Methods
`We searched the L:Drive on November 13, 2014 using the term, olopatadine to identify reviews
`previously performed by DMEPA.
`
`C.2
`
`Results
`
`A proprietary name review was completed on May 19, 20142 and August 20, 20133 for
`olopatadine hydrochloride under IND 060991.
`
`
`2 Kapoor R and Maslov Y. Proprietary Name Review for PAZEO (IND 060991). Silver Spring (MD): Food and Drug
`Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of
`Medication Error Prevention and Analysis (US); 2014 05 19. 21 p. OSE RCM No.: 2013-16781.
`3 Lee J and Wilkins-Parker J. Proprietary Name Review for SABERO (IND 060991). Silver Spring (MD): Food and
`Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of
`Medication Error Prevention and Analysis (US); 2013 08 20. 40 p. OSE RCM No.: 2013-597.
`
`8
`
`Reference ID: 3660746
`
`

`

`APPENDIX D. NOT APPLICABLE
`
`ISMP NEWSLETTERS
`APPENDIX E.
`E.1 Methods
`We searched the Institute for Safe Medication Practices (ISMP) newsletters on November 13,
`2014 using the criteria below, and then individually reviewed each newsletter. We limited our
`analysis to newsletters that described medication errors or actions possibly associated with the
`label and labeling.
`
`ISMP Newsletters Search Strategy
`ISMP Newletter(s)
`Search Strategy and
`Terms
`
`Match Exact Word or Phrase: olopatadine
`
`E.2
`
`Results
`
`Our search identified two articles in ISMP Medication Safety Alert4,5 that were specific to the
`currently marketed product Patanol which is olopatadine hydrochloride 0.1% ophthalmic
`solution. One article4 specifically discussed name confusion with Patanol and another product
`and the other article5 was associated with the advertisement of Patanol. Therefore, neither
`article is relevant to this review.
`
`
`4 Institute for Safe Medication Practices. Safety Briefs. ISMP Med Saf Alert. 1997;2(1):1-2.
`5 Institute for Safe Medication Practices. Drug ad promotes sharing eye drops. ISMP Med Saf Alert Acute Care.
`2004;9(20):1-3.
`
`9
`
`Reference ID: 3660746
`
`3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`(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/
`----------------------------------------------------
`
`RACHNA KAPOOR
`11/19/2014
`
`YELENA L MASLOV
`11/19/2014
`
`Reference ID: 3660746
`
`

`

`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]
`
`Application Information
`NDA Supplement #:S- N/A
`Efficacy Supplement Type SE- N/A
`NDA # 206276
`BLA Supplement # N/A
`BLA# N/A
`Proprietary Name: Per e-mail sent to Lois Almoza of Division of Transplant and Ophthalmology Products (DTOP) on
`October 8, 2014, Applicant plans to submit request for proprietary name review on or before October 15, 2014. A letter issued to the
`Applicant on May 21, 2014 by Office of Surveillance and Epidemiology (OSE) under IND 060991 noting the proposed proprietary name,
`Pazeo was conditionally acceptable and would need to be submitted for review again once the NDA was submitted.
`Established/Proper Name: olopatadine hydrochloride
`Dosage Form: ophthalmic solution
`Strengths: 0.7%
`Applicant: Alcon Research, Ltd.
`Agent for Applicant (if applicable): N/A
`Date of Application: July 30, 2014
`Date of Receipt: July 30, 2014
`Date clock started after UN: N/A
`PDUFA Goal Date: January 30, 2015
`Action Goal Date (if different):
`Date of Filing Meeting: September 26, 2014
`Filing Date: September 28, 2014
`Chemical Classification: (1,2,3 etc.) (original NDAs only) 5
`Proposed indication/Proposed change(s): treatment of ocular itching associated with allergic
`conjunctivitis
`
`Type of Original NDA:
`AND (if applicable)
`Type of NDA Supplement:
`
`
`
`If 505(b)(2): Draft the “505(b)(2) Assessment” review found at:
`http://inside.fda.gov:9003/CDER/OfficeofNewDrugs/ImmediateOffice/UCM027499.
`
`Type of BLA
`
`If 351(k), notify the OND Therapeutic Biologics and Biosimilars Team
`Review Classification:
`
`505(b)(1)
`505(b)(2)
`505(b)(1)
`505(b)(2)
`
`351(a)
`351(k)
`
` Standard
` Priority
`
`If the application includes a complete response to pediatric WR, review
`classification is Priority.
`
`If a tropical disease priority review voucher or pediatric rare disease
`priority review voucher was submitted, review classification is Priority.
`
`Resubmission after withdrawal? N/A
`Part 3 Combination Product? N/A
`
`If yes, contact the Office of
`Combination Products (OCP) and copy
`them on all Inter-Center consults
`
` Tropical Disease Priority
`Review Voucher submitted
` Pediatric Rare Disease Priority
`Review Voucher submitted
`Resubmission after refuse to file? N/A
`Convenience kit/Co-package
`Pre-filled drug delivery device/system (syringe, patch, etc.)
`Pre-filled biologic delivery device/system (syringe, patch, etc.)
`Device coated/impregnated/combined with drug
`Device coated/impregnated/combined with biologic
`Separate products requiring cross-labeling
`Drug/Biologic
`
`Version: 4/15/2014
`
`Reference ID: 3641503
`
`1
`
`

`

`Possible combination based on cross-labeling of separate
`products
`Other (drug/device/biological product)
`
` Fast Track Designation
` Breakthrough Therapy Designation
`(set the submission property in DARRTS and
`notify the CDER Breakthrough Therapy
`Program Manager)
` Rolling Review
` Orphan Designation
`
` Rx-to-OTC switch, Full
` Rx-to-OTC switch, Partial
` Direct-to-OTC
`
`PMC response
`PMR response:
`FDAAA [505(o)]
`PREA deferred pediatric studies [21 CFR
`314.55(b)/21 CFR 601.27(b)]
` Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
`Animal rule postmarketing studies to verify clinical
`benefit and safety (21 CFR 314.610/21 CFR 601.42)
`
`Other: N/A
`Collaborative Review Division (if OTC product): N/A
`List referenced IND Number(s): 060991
`Goal Dates/Product Names/Classification Properties YES NO NA Comment
`PDUFA and Action Goal dates correct in tracking system?
`
`If no, ask the document room staff to correct them immediately.
`These are the dates used for calculating inspection dates.
`Are the proprietary, established/proper, and applicant names
`correct in tracking system?
`
`If no, ask the document room staff to make the corrections. Also,
`ask the document room staff to add the established/proper name
`to the supporting IND(s) if not already entered into tracking
`system.
`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 NDAs/NDA supplements, check
`the New Application and New Supplement Notification Checklists
`for a list of all classifications/properties at:
`http://inside.fda.gov:9003/CDER/OfficeofBusinessProcessSupport/ucm163969.ht
`m
`
`If no, ask the document room staff to make the appropriate
`entries.
`Application Integrity Policy
`Is the application affected by the Application Integrity Policy
`(AIP)? Check the AIP list at:
`http://www.fda.gov/ICECI/EnforcementActions/ApplicationIntegrityPolicy/default
`.htm
`If yes, explain in comment column.
`
`If affected by AIP, has OC/OMPQ been notified of the
`submission? If yes, date notified:
`
`Version: 4/15/2014
`
`Reference ID: 3641503
`
`Review Priority:P
`
`YES NO NA Comment
`
`X
`
`X
`
`2
`
`

`

`User Fees
`Is Form 3397 (User Fee Cover Sheet) included with
`authorized signature?
`
`YES NO NA Comment
`
`User Fee Status
`
`Payment for this application:
`
`If a user fee is required and it has not been paid (and it
`is not exempted or waived), the application is
`unacceptable for filing following a 5-day grace period.
`Review stops. Send Unacceptable for Filing (UN) letter
`and contact user fee staff.
`
`Paid
`Exempt (orphan, government)
`Waived (e.g., small business, public health)
`Not required
`
`Note: Receipt date for user fee is May 15, 2014
`Payment of other user fees:
`
`Not in arrears
`In arrears
`
`YES NO NA Comment
`
`If the firm is in arrears for other fees (regardless of
`whether a user fee has been paid for this application),
`the application is unacceptable for filing (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the user fee staff.
`505(b)(2)
`(NDAs/NDA Efficacy Supplements only)
`Is the application for a duplicate of a listed drug and eligible
`for approval under section 505(j) 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(b)(1)].
`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)]?
`
`If you answered yes to any of the above questions, the application
`may be refused for filing under 21 CFR 314.101(d)(9). Contact
`the 505(b)(2) review staff in the Immediate Office of New Drugs
`Is there unexpired exclusivity on any drug product containing
`the active moiety (e.g., 5-year, 3-year, orphan, or pediatric
`exclusivity)?
`Check the Electronic Orange Book at:
`http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm
`
`If yes, please list below:
`Application No.
`
`Drug Name
`
`Exclusivity Code
`
`Exclusivity Expiration
`
`Version: 4/15/2014
`
`Reference ID: 3641503
`
`3
`
`

`

`If there is unexpired, 5-year exclusivity remaining on the active moiety for the proposed drug product, a 505(b)(2)
`application cannot be submitted until the period of exclusivity expires (unless the applicant provides paragraph IV
`patent certification; then an application can be submitted four years after the date of approval.) Pediatric
`exclusivity will extend both of the timeframes in this provision by 6 months. 21 CFR 314.108(b)(2). Unexpired, 3-
`year exclusivity may block the approval but not the submission of a 505(b)(2) application.
`Exclusivity
`YES NO NA Comment
`Does another product (same active moiety) have orphan
`exclusivity for the same indication? Check the Orphan Drug
`Designations and Approvals list at:
`http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm
`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)]?
`
`Requested 3-year
`Exclusivity in
`submission received
`July 30, 2014.
`
`If yes, consult the Director, Division of Regulatory Policy II,
`Office of Regulatory Policy
`Has the applicant requested 5-year or 3-year Waxman-Hatch
`exclusivity? (NDAs/NDA efficacy supplements only)
`
`If yes, # years requested: 3
`
`Note: An applicant can receive exclusivity without requesting it;
`therefore, requesting exclusivity is not required.
`Is the proposed product a single enantiomer of a racemic drug
`previously approved for a different therapeutic use (NDAs
`only)?
`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
`FDAAA Section 1113)?
`
`If yes, contact the Orange Book Staff (CDER-Orange Book
`Staff).
`For BLAs: Has the applicant requested 12-year exclusivity
`under section 351(k)(7) of the PHS Act?
`
`If yes, notify Marlene Schultz-DePalo, OBP Biosimilars RPM
`
`Note: Exclusivity requests may be made for an original BLA
`submitted under Section 351(a) of the PHS Act (i.e., a biological
`reference product). A request may be located in Module 1.3.5.3
`and/or other sections of the BLA and may be included in a
`supplement (or other correspondence) if exclusivity has not been
`previously requested in the original 351(a) BLA. An applicant can
`receive exclusivity without requesting it; therefore, requesting
`exclusivity is not required.
`
`Format and Content
`
`All paper (except for COL)
`All electronic
`
`4
`
`Version: 4/15/2014
`
`Reference ID: 3641503
`
`

`

`Mixed (paper/electronic)
`
`CTD
`Non-CTD
`Mixed (CTD/non-CTD)
`
`YES NO NA Comment
`
`Do not check mixed submission if the only electronic component
`is the content of labeling (COL).
`
`If mixed (paper/electronic) submission, which parts of the
`application are submitted in electronic format?
`Overall Format/Content
`If electronic submission, does it follow the eCTD
`guidance?1
`If not, explain (e.g., waiver granted).
`Index: Does the submission contain an accurate
`comprehensive index?
`Is the submission complete as required under 21 CFR 314.50
`(NDAs/NDA efficacy supplements) or under 21 CFR 601.2
`(BLAs/BLA efficacy supplements) including:
`
`legible
`English (or translated into English)
`pagination
`navigable hyperlinks (electronic submissions only)
`
`If no, explain.
`BLAs only: Companion application received if a shared or
`divided manufacturing arrangement?
`
`If yes, BLA #
`
`Forms and Certifications
`Electronic forms and certifications with electronic signatures (scanned, digital, or electronic – similar to DARRTS,
`e.g., /s/) are acceptable. Otherwise, paper forms and certifications with hand-written signatures must be included.
`Forms include: user fee cover sheet (3397), application form (356h), patent information (3542a), financial
`disclosure (3454/3455), and clinical trials (3674); Certifications include: deb