CENTER FOR DRUG EVALUATION AND
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`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
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`APPLICATION NUMBER:
`22-264
`22-264
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`APPLICA TION NUMBER:
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`APPROVAL LETTER
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`APPROVAL LETTER
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`DEPARTMENT OF HEALTH AND HUMAN
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`Public Health Service
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`Food and Drug Administration
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` Rockville, MD 20857
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`NDA APPROVAL
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`NDA 22-264
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`Ortho-McNeil-Jansen Pharmaceuticals, Inc.
`Attention: Rodney Malchow
`Associate Director, Regulatory Affairs
`1125 Trenton-Harbourton Road
`P.O. Box 200
`Titusville, N.J. 80560
`
`Dear Mr. Malchow:
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` Please refer to your new drug application (NDA) dated October 25, 2007, received October 26,
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`2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Invega
`Sustenna (paliperidone palmitate) 39mg, 78mg, 117mg, 156mg, and 234 mg extended-release
`injectable suspension.
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`We acknowledge receipt of your submissions and communications dated February 2, 2009,
`February 11, 2009, February 24, 2009, March 24, 2009, May 7, 2009, May 15, 2009, May 20,
`2009, May 22, 2009, June 9, 2009, June 22, 2009, June 26, 2009, July 10, 2009, July 15, 2009,
`July 16, 2009, July 20, 2009 and July 23, 2009.
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`Your February 2, 2009 submission constituted a complete response to our August 25, 2008
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`action letter.
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`This new drug application provides for the use of Invega Sustenna (paliperidone palmitate)
`extended-release injectable suspension for the acute and maintenance treatment of schizophrenia
`in adults.
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`We have completed our review of this application. It is approved, effective on the date of this
`letter, for use as recommended in the enclosed agreed-upon labeling text.
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`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.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, please submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm155657.htm. that is
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`identical to the enclosed agreed-upon labeling text. Upon receipt, we will transmit that version
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`

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`NDA 22-264
`Page 2
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`to the National Library of Medicine for public dissemination. For administrative purposes,
`please designate this submission, “SPL for approved NDA 22-264.”
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels as agreed upon in your communication dated
`July 29, 2009 as soon as they are available, but no more than 30 days after they are printed.
`Please submit these labels electronically according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications
`and Related Submissions Using the eCTD Specifications (October 2005). 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 22-264.” Approval of this submission by FDA is
`not required before the labeling is used.
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`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.
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`PROPRIETARY NAME
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`The Division of Medication Error Prevention and Analysis (DMEPA) and the Division of
`Psychiatry Products do not object to the use of the proprietary name, Invega Sustenna, for this
`product.
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new dosage forms, new indications, new routes of administration, and new
`dosing regimens 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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`We are waiving the pediatric study requirement for ages 0 to 12 years because necessary studies
`are impossible or highly impracticable due to the very low incidence of schizophrenia diagnosed
`prior to age 13.
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`We are deferring submission of your pediatric studies for ages 13 to 17 years because pediatric
`studies in this age group should be delayed until additional safety and effectiveness data have
`been collected. Studies for the extended-release injectable suspension are deferred until studies
`currently being conducted under the adolescent schizophrenia development program are
`complete.
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`Your deferred pediatric studies required by section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act are required postmarketing studies. The status of these 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. These required studies are listed below.
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`1. A deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients
`ages 13 to 17. A study to obtain pharmacokinetic data and provide information pertinent to
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`Final Protocol Submission:
`Study Completion Date:
`Final Report Submission:
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`by June 1, 2011
`by November 1, 2013
`by January 1, 2014
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`by November 1, 2013
`by April 1, 2015
`by October 1, 2016
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`Final Protocol Submission:
`Study Completion Date:
`Final Report Submission:
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`NDA 22-264
`Page 3
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`dosing of paliperidone palmitate extended-release injectable suspension in the relevant pediatric
`population. This study will be initiated after submission of the reports from the ongoing
`pediatric oral paliperidone studies to support use of paliperidone in adolescents aged 13 – 17.
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`2. A deferred pediatric study under PREA for the treatment of schizophrenia in pediatric patients
`ages 13 to 17. A study of the efficacy and safety of paliperidone palmitate extended-release
`injectable suspension in the relevant pediatric population.
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`Submit clinical protocols to your IND for this product. Submit final reports to your NDA
`22-264. Use the following designator to prominently label all submissions:
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`POSTMARKETING COMMITMENTS NOT SUBJECT TO REPORTING
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`REQUIREMENTS UNDER SECTION 506B
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`We remind you of the following postmarketing commitment agreed upon in our communication
`dated July 20, 2009.
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`3. You have committed to adding a clearly visible fill line to the syringe barrel so that the health
`care provider can ensure that the syringes contain the required volume of suspension prior to
`administration and that no gross leakage or evaporation of the syringe contents has occurred
`during storage or shipping. We request that this change be carried out, and a prior approval
`supplement be submitted within one year of approval.
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`Completion date:
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`Under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary of
`each commitment in your annual report to this NDA. The status summary should include
`expected summary completion and final report submission dates, any changes in plans since the
`last annual report, and, for clinical studies, number of patients entered into each study. All
`submissions, including supplements, relating to this postmarketing study commitment should be
`prominently labeled “Postmarketing Commitment Protocol”, “Postmarketing Commitment
`Final Report”, or “Postmarketing Commitment Correspondence.”
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`PROMOTIONAL MATERIALS
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`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
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`Required Pediatric Assessment(s)
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`by August 2010
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`

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`NDA 22-264
`Page 4
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`proposed materials in draft or mock-up form with annotated references, and the package insert(s)
`to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`NMT
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert(s), at the time of initial dissemination or publication, accompanied by a Form
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`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 Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see www.fda.gov/cder/ddmac.
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`DISSOLUTION METHOD AND SPECIFICATIONS
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`The dissolution method and specifications for all strengths of the extended-release injectable
`suspension should be:
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`Parameter
`Apparatus Type
`Media
`Volume
`Temperature
`Frequency
`Sampling Times
`Acceptance Criteria
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`Dissolution Method and Specification
`USP Type II (paddle)
`0.001 M HCl containing 0.489% Polysorbate 20 (Tween®20)
`900 ml
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`25 ± 0.5 °C
`50 rpm
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`1.5, 8, 20, and 45 minutes
`1.5 minutes
`8 minutes
`20 minutes
`45 minutes
`HPLC UV detection
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`of Label Claim
`of Label Claim
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`of Label Claim
`of Label Claim
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`Analysis
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`EXPIRY
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`A 24 month expiry date is granted based on the available stability data.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and a copy to the following address:
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`MedWatch
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`Food and Drug Administration
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`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`NDA 22-264
`Page 5
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` REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA (21
`CFR 314.80 and 314.81).
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`If you have any questions, call Kimberly Updegraff, M.S., Senior Regulatory Project Manager,
`at (301) 796-2201.
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` Enclosure (labeling)
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`Sincerely,
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` {See appended electronic signature page}
`
`Thomas Laughren, M.D.
`
` Director
`Division of Psychiatry Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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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/
`----------------------------------------------------
`
`THOMAS P LAUGHREN
`07/31/2009
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