`CENTER FOR DRUG EVALUATION AND RESEARCH
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`Approval Package for:
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`APPLICATION NUMBER:
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`204592Orig1s000
`
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` Zorvolex Capsules 18 mg and 35 mg.
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`diclofenac
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`Iroko Pharmaceuticals LLC.
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`October 18, 2013
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`For the treatment of mild to moderate acute pain in
`adults.
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`Trade Name:
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`Generic Name:
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`Sponsor:
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`Approval Date:
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`Indications:
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`

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`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`204592Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology / Virology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
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`X
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`X
`X
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`X
`X
`X
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`X
`X
`X
`X
`X
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`X
`X
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`

`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`
`
`APPLICATION NUMBER:
`204592Orig1s000
`APPROVAL LETTER
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`

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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 204592
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`
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
`
`Steve Jensen
`Sr. VP, Regulatory Affairs & Quality
`
`
`Iroko Pharmaceuticals LLC
`One Kew Place
`15- Rouse Boulevard
`Philadelphia, PA 19112
`
`Attention:
`
`
`
`Dear Mr. Jensen:
`
`Please refer to your New Drug Application (NDA) dated and received December 20, 2012,
`submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for Zorvolex (diclofenac) Capsules 18 mg and 35 mg.
`
`We acknowledge receipt of your amendments dated January 30, February 4 and 12, March 6,
`April 8 and 30, August 15, 23, and 30, and October 1 and 10, 2013.
`
`Reference is also made to your email dated Oct. 18, 2013, which included the final agreed-upon
`labeling.
`
`This new drug application provides for the use of Zorvolex (diclofenac) Capsules 18 mg and 35
`mg for the treatment of mild to moderate acute pain in adults.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the agreed-upon labeling text.
`
`WAIVER OF HIGHLIGHTS SECTION
`
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`
`
`
`Reference ID: 3392875
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`

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`NDA 204592
`Page 2
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`of labeling must be identical to the enclosed labeling text for the package insert and Medication
`Guide. Information on submitting SPL files using eLIST may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As, available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton and immediate container labels that are identical to the enclosed
`carton and immediate container labels, as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labels electronically according to the guidance for
`industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical
`Product Applications and Related Submissions Using the eCTD Specifications (June 2008).
`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
`heavy-weight paper or similar material. For administrative purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 204592.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`MARKET PACKAGE
`
`Please submit one market package of the drug product when it is available to the following
`address:
`
`
`Swati Patwardhan
`Food and Drug Administration
`Center for Drug Evaluation and Research
`White Oak Building 22, Room: 3170
`10903 New Hampshire Avenue
`Silver Spring, Maryland
`Use zip code 20903 if shipping via United States Postal Service (USPS).
`Use zip code 20993 if sending via any carrier other than USPS (e.g., UPS, DHL, FedEx).
`
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`
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`Reference ID: 3392875
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`

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`NDA 204592
`Page 3
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`We are waiving the pediatric study requirement for ages birth to less than 12 months because
`there is evidence strongly suggesting that the drug product would be unsafe in this pediatric
`group.
`
`We are deferring submission of your pediatric studies for ages 1 year to less than 17 years for
`this application because this product is ready for approval for use in adults and the pediatric
`studies have not been completed.
`
`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act/FDCA are required postmarketing studies. The status of the postmarketing studies
`must be reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Federal
`Food, Drug, and Cosmetic Act/FDCA. The required studies are listed below.
`
`
`2091-1 An open-label pharmacokinetic and safety study or studies of an age-
`appropriate formulation of Zorvolex in pediatric patients 6 years to less than
`17 years of age with acute pain.
`
`The timetable you submitted on August 30, 2013, states that you will conduct
`this study according to the following schedule:
`
`Final Protocol Submission: November 1, 2014
`Study/Trial Completion: May 3, 2015
`Final Report Submission: May 3, 2017
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`2091-2 An open-label pharmacokinetic and safety study or studies of an age-
`appropriate formulation of Zorvolex in pediatric patients 2 years to less than 6
`years of age with acute pain.
`
`The timetable you submitted on August 30, 2013, states that you will conduct
`this study according to the following schedule:
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
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`June 6, 2015
`January 6, 2016
`January 6, 2018
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`2091-3 A pharmacokinetic, safety, and efficacy study or studies of an age-appropriate
`formulation of Zorvolex in pediatric patients 1 year to less than 2 years of age
`with acute pain.
`
`The timetable you submitted on August 30, 2013, states that you will conduct
`this study according to the following schedule:
`
`Final Protocol Submission:
`Study/Trial Completion:
`Final Report Submission:
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`January 6, 2018
`July 30, 2018
`July 30, 2020
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`Reference ID: 3392875
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`

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`NDA 204592
`Page 4
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`Submit the protocol(s) to your IND 103880, with a cross-reference letter to this NDA.
`
`Reports of these required pediatric postmarketing studies must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`EXPIRY DATING PERIOD
`
` 24-month expiry dating period is granted for Zorvolex (diclofenac) Capsules 18 mg and 35 mg
`when stored at 25°C (77°F) with excursions permitted from 15° to 30°C (59° to 86°F).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
` A
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`
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`Reference ID: 3392875
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`

`

`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Sharon Hertz, MD
`Deputy Director
`Division of Anesthesia, Analgesia,
` and Adduction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
`
`NDA 204592
`Page 5
`
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`If you have any questions, call Swati Patwardhan, Regulatory Project Manager, at (301) 796-
`4085.
`
`
`
`Enclosure(s):
`Content of Labeling
`Carton and Container Labeling
`
`
`
`Reference ID: 3392875
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`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SHARON H HERTZ
`10/18/2013
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`Reference ID: 3392875
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`