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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING COMMITMENT
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` NDA 22249/ S-014
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`Reference ID: 3364393
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` Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries, Ltd.
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`Attention: Michael McGraw, PharmD, MS
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`Manager, Regulatory Affairs
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`41 Moores Road
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`P.O. Box 4011
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`Frazer, PA 19355
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`Dear Dr. McGraw:
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`Please refer to your Supplemental New Drug Application (sNDA) dated February 28, 2013,
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`received February 28, 2013, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for TREANDA® (bendamustine hydrochloride) Lyophilized Solid for
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`Injection, 25 mg/vial; 100 mg/vial.
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`We acknowledge receipt of your amendment dated August 27, 2013.
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`This “Prior Approval” supplemental new drug application provides for revisions to the labeling
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`based on the QTc study report, submitted as part of post marketing commitment PMC #379-3, in
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`which Cephalon committed to conducting a study to assess the potential for bendamustine to
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`prolong the QT interval in patients.
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`We also refer to our Post Marketing Commitment/ Supplement Request letter dated December 7,
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`2011 in which we acknowledged fulfillment of PMC 379-2 that provided for ADME Study 1039
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`titled “An Open-Label Study to Investigate the Pharmacokinetics (Distribution, Metabolism, and
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`Excretion) of Bendamustine Hydrochloride Following Intravenous Infusion of
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`[14C]Bendamustine Hydrochloride in Patients With Relapsed or Refractory Malignancy
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`(Hematologic or Non-hematologic)”. In that letter we requested that you update the labeling to
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`include the results from ADME study 1039. This supplement also provides for those updates to
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`Section 12.3, Pharmacokinetics, based on ADME study 1039.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
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`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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`text.
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` NDA 22249/S-014
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` Page 2
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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, submit the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert), with the
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`addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as
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`well as annual reportable changes not included in the enclosed labeling.
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` Information on submitting SPL files using eList may be found in the guidance for industry titled
` “SPL Standard for Content of Labeling Technical Qs and As at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`date(s).
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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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`FULFILLMENT OF POSTMARKETING COMMITMENT
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`We have received your submission dated February 28, 2013, containing the final report for the
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`following postmarketing commitment listed in the March 20, 2008 approval letter.
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`PMC 379-3 Cephalon commits to conducting a study to assess the potential for bendamustine
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`to prolong the QT interval in patients. The QT plan will be submitted prior to
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`initiation for IRT review and concurrence.
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`Protocol Submission:
`July 2008
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`Study Start:
`December 2008
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`Reference ID: 3364393
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` NDA 22249/S-014
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` Page 3
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` Final Report Submission:
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` June 2010
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`We have reviewed your submission and conclude that the above commitment was fulfilled.
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`This completes all of your postmarketing requirements and postmarketing commitments
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`acknowledged in our March 20, 2008 letter.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
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`(3) the package insert(s) to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
` instructions are provided on page 2 of the form. For more information about submission of
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` promotional materials to the Office of Prescription Drug Promotion (OPDP), see
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` http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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` REPORTING REQUIREMENTS
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` We remind you that you must comply with reporting requirements for an approved NDA
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` (21 CFR 314.80 and 314.81).
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` If you have any questions, call Theresa Carioti, Regulatory Project Manager, at (301) 796-2848.
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`ENCLOSURE:
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`Content of Labeling
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`Reference ID: 3364393
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`Sincerely,
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`{See appended electronic signature page}
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`Robert C. Kane, M.D.
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`Deputy Director for Safety
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`Division of Hematology Products
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`Office of Hematology and Oncology Products
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`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/
`----------------------------------------------------
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`ROBERT C KANE
`08/28/2013
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`Reference ID: 3364393
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