DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 208194/S-001 NDA 208194/S-002 SUPPLEMENT APPROVAL Eagle Pharmaceuticals, Inc. Attention: Foma Rashkovsky Senior Director, Regulatory Affairs 50 Tice Boulevard, Suite 315 Woodcliff Lake, NJ 07677 Dear Mr. Rashkovsky: Please refer to your Supplemental New Drug Applications (sNDA), supplement 001 dated December 23, 2015, received December 23, 2015, and supplement 002 dated December 28, 2015, received December 28, 2015; and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for BendekaTM (bendamustine hydrochloride) Injection, 100 mg/4 mL (25 mg/mL). Supplement 001 is a “Changes Being Effected” supplemental new drug application providing for updates to the Highlights Suspected Adverse Reactions section of the United States Prescribing Information (USPI) changing the reporting phone number and company name from Eagle Pharmaceuticals, Inc. to Teva Pharmaceuticals. In addition, revisions were made in the USPI to be consistent with the Reference Listed Drug. Supplement 002 is a “Prior Approval” supplemental new drug application providing for updates to the Highlights Recent Major Changes; addition of infection information in Warnings and Precautions; and addition of post-marketing experience in Adverse Reactions sections. In addition, the labeling has been revised with additional instructional statements and information related to the preparation and storage of Bendeka. 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. 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: 3949985 NDA 208194/S-001 NDA 208194/S-002 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 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 from publicly available labeling repositories. Also within 14 days, amend all pending supplemental applications that includes labeling changes 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 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 markedup 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 this drug product for this indication has an orphan drug designation, 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: 3949985 NDA 208194/S-001 NDA 208194/S-002 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, call Laura Wall, Regulatory Project Manager, at (301) 796-2237. 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: 3949985 --------------------------------------------------------------------------------------------------------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 06/23/2016 Reference ID: 3949985