`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 022249/S-023
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`
`
`
`Cephalon, Inc. (a wholly owned subsidiary of Teva Pharmaceutical Industries, Ltd.)
`Attention: Nina Moore
`Associate Director, Regulatory Affairs
`41 Moores Road, P.O. Box 4011
`Frazer, PA 19355
`
`
`Dear Ms. Moore:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated October 3, 2017,
`received October 3, 2017, and your amendments, submitted under section 505(b) of the Federal
`Food, Drug, and Cosmetic Act (FDCA) for TREANDA® (bendamustine hydrochloride)
`Injection, 45 mg/0.5mL or 180 mg/2mL, and TREANDA® (bendamustine hydrochloride) for
`Injection, 25 mg or 100 mg.
`
`This “Changes Being Effected” supplemental new drug application provides for updates to
`Sections 8.6 Renal Impairment, 8.7 Hepatic Impairment, and 12.3 Pharmacokinetics of the
`United States Prescribing Information based on the analysis that showed that renal function
`[creatinine clearance (CrCL) range: 30 to 80 mL/min] does not influence exposure to
`bendamustine, and bendamustine has not been studied in patients with moderate or severe
`hepatic impairment.
`
`APPROVAL & LABELING
`
`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, 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
`
`Reference ID: 4196300
`
`
`
`NDA 022249/S-023
`Page 2
`
`
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to, except with the revisions listed, the enclosed labeling (text for
`the package insert,) with the addition of any labeling changes in pending “Changes Being
`Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
`labeling.
`
`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
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
`supplements for which FDA has not yet issued an action letter, with the content of labeling
`[21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes with the revisions
`listed approved in this supplemental application, as well as annual reportable changes, and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
`
`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.
`
`Because none of these criteria apply to your application, you are exempt from this requirement.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`
`Reference ID: 4196300
`
`
`
`NDA 022249/S-023
`Page 3
`
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf).
`
`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. 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.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, contact me at katie.chon@fda.hhs.gov or (240) 402-6578.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Ann T. Farrell, MD
`Director
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`
`ENCLOSURE:
`Content of Labeling
`
`Reference ID: 4196300
`
`
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ANN T FARRELL
`12/15/2017
`
`Reference ID: 4196300
`
`