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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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`NDA 205580
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`TENTATIVE APPROVAL
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`Eagle Pharmaceuticals, Inc.
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`Attention: Foma Rashkovsky
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`Senior Director, Regulatory Affairs
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`50 Tice Boulevard, Suite 315
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`Woodcliff Lake, NJ 07677
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`Dear Mr. Rashkovsky:
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`Please refer to your New Drug Application (NDA) dated September 6, 2013, received
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`September 6, 2013, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and
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`Cosmetic Act for bendamustine hydrochloride injection.
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`We refer to your initial submission dated June 30, 2013, received on July 1, 2013, and our
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`Refuse to File letter dated August 28, 2013. Your September 6, 2013 submission was in
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`response to our Refuse-to-File letter.
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`We acknowledge receipt of your amendments dated October 14, November 11, 26, December
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`27, 2013; January 8 (2), 27, 30, February 6, 10, March 7, 31, April 1, 7, 11, 25, May 5, 7, 9,
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`13, and June 18, 26, 2014.
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`This NDA provides for the use of bendamustine hydrochloride injection for Indolent Non-
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`Hodgkin Lymphoma (NHL).
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`We have completed our review of this application, as amended. It is tentatively approved under
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`21 CFR 314.105 for use as recommended in the agreed-upon enclosed labeling (text for the
`package insert and carton and immediate container labels) and/or submitted labeling (text for the
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`package insert submitted June 26, 2014 and carton and immediate container labels submitted
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`April 25, 2014). This determination is based upon information available to the Agency at this
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`time, [i.e., information in your application and the status of current good manufacturing practices
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`(cGMPs) of the facilities used in the manufacture and testing of the drug product]. This
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`determination is subject to change on the basis of any new information that may come to our
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`attention.
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`The listed drug upon which your application relies is subject to a period of patent protection, and
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`therefore final approval of your application under section 505(c)(3) of the Federal Food, Drug,
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`and Cosmetic Act (the Act) [21 U.S.C. 355(c)(3)] may not be made effective until the patent
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`protection period has expired.
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`Reference ID: 3534564
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` NDA 205580
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` Page 2
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` Your application contains certifications to each of the patents under section 505(b)(2)(A)(iv) of
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` the Act stating that the patents are invalid, unenforceable, or will not be infringed by your
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` manufacture, use, or sale of, this drug product under this application (Paragraph IV
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` certifications).
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`Section 505(c)(3)(C) of the Act provides that approval of a new drug application submitted
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`pursuant to section 505(b)(2) of the Act shall be made effective immediately, unless an action is
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`brought for infringement of one or more of the patents that were the subject of the paragraph IV
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`certifications. This action must be taken prior to the expiration of forty-five days from the date
`the notice provided under section 505(b)(3) is received by the patent owner/approved application
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` holder. You notified us that you complied with the requirements of section 505(b)(3) of the Act.
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`In addition, you have notified the Agency that the patent owner and/or approved application
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`holder has initiated a patent infringement suit against you with respect to U.S. Patent No.
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`8,445,524 (524 patent) in the United States District Court, District of Delaware.
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`Finally, the Orphan Drug provisions of the Act [21 U.S.C. §§ 360aa-360dd] provide for a grant
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`of seven years of market exclusivity to which a period of pediatric exclusivity may attach.
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`Orphan drug exclusivity blocks approval of any other application for the same drug for the same
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`indication. Cephalon Inc.’s product, TREANDA (bendamustine hydrochloride) has orphan drug
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`exclusivity that currently blocks approval of your application.
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`Therefore, final approval of your application cannot be granted until the expiration of:
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`1. a. the 30-month period provided for in Section 505(c)(3)(C) beginning on the date of
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`receipt of the 45-day notice required under Section 505(b)(3), unless the court has
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`extended or reduced the period because of the failure of either party to reasonably
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`cooperate in expediting the action, or
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`b. the date the court decides that the 524 patent is invalid or not infringed as
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`described in section 505(c)(3)(C)(i), (ii), (iii,) or (iv) of the Act, or,
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`c. the 524 patent has expired; and
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`2. TREANDA’s orphan drug exclusivity period.
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`In addition, we will not grant final approval until we are assured there is no new information that
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`would affect whether final approval should be granted.
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`To obtain final approval of this application, submit an amendment two or six months prior to the:
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`1) expiration of the patents and/or exclusivity protection or 2) date you believe that your NDA
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`will be eligible for final approval, as appropriate. In your cover letter, clearly identify your
`amendment as “REQUEST FOR FINAL APPROVAL.” This amendment should provide the
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`legal/regulatory basis for your request for final approval and should include a copy of any
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`relevant court order or judgment settlement, or licensing agreement, as appropriate. In addition
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`to a safety update, the amendment should also identify changes, if any, in the conditions under
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`which your product was tentatively approved, i.e., updated labeling; chemistry, manufacturing,
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`and controls data; and risk evaluation and mitigation strategy (REMS). If there are no changes,
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`clearly state so in your cover letter. Any changes require our review before final approval and
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`the goal date for our review will be set accordingly.
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`Reference ID: 3534564
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` NDA 205580
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` Page 3
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` Until we issue a final approval letter, this NDA is not deemed approved.
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` Please note that this drug product may not be marketed in the United States without final agency
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` approval under Section 505 of the Act. The introduction or delivery for introduction into
` interstate commerce of this drug product before the final approval date is prohibited under
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` Section 501 of the Act and 21 U.S.C. 331(d).
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`PROPRIETARY NAME
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`If you intend to have a proprietary name for this product, the name and its use in the labels must
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`conform to the specifications under 21 CFR 201.10 and 201.15. We recommend that you submit
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`a request for a proposed proprietary name review. See the guidance for industry titled,
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`“Contents of a Complete Submission for the Evaluation of Proprietary Names,” at
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u
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`cm075068.pdf and “PDUFA Reauthorization Performance Goals and Procedures Fiscal Years
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`2008 through 2012.”
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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 in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`We note that if this application is ultimately approved, you will need to meet these requirements.
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`If you have any questions, call Laura Wall, Regulatory Project Manager, at (301) 796-2237.
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`Sincerely,
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` {See appended electronic signature page}
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` Ann T. Farrell, MD
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` Division Director
` 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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`ENCLOSURE(S):
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`Content of Labeling
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`Carton and Container Labeling
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`Reference ID: 3534564
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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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`ANN T FARRELL
`07/02/2014
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`Reference ID: 3534564
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