`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`
`
`Approval Package for:
`
`
`
`APPLICATION NUMBER:
`NDA 208194/S-004
`
`
`
`
` Name: BendekaTM (bendamustine hydrochloride)
`Injection, 100 mg/4 mL (25 mg/mL).
`
`Sponsor: Eagle Pharmaceuticals, Inc.
`
`
`
`
` Approval Date: February 6, 2017
`
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`
`
`
`APPLICATION NUMBER:
`NDA 208194/S-004
`
`
`CONTENTS
`
`
`Reviews / Information Included in this Review
`
`
`
`Approval Letter
`Approvable Letter
`Labeling
`Division Director’s Memo
`Labeling Review(s)
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology / Toxicology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology & Biopharmaceutics Review(s)
`Other Review(s)
`Administrative and Correspondence Documents
`
`
`
`
`X
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`
`
`
`
`X
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`
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`
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`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`
`
`
`APPLICATION NUMBER:
`NDA 208194/S-004
`NDA 208194/8-004
`
`
`
`APPLICA TION NUMBER:
`
`
`
`
`
`
`APPROVAL LETTER
`
`APPROVAL LETTER
`
`
`
`6*” ”Mt";
`
`g __/CDEPARTMENT OFHEALTH ANDHUMAN SERVICES
`
`2,a.
`”W
`
`NDA 208194/S-004
`
`Eagle Pharmaceuticals, Inc.
`Attention: Adrian Hepner, MD, PhD
`Chief Medical Officer
`
`50 Tice Boulevard, Suite 315
`
`Woodcliff Lake, NJ 07677
`
`Dear Dr. Hepner:
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`APPROVAL LETTER
`
`Please refer to your Supplemental New Drug Application (sNDA) dated November 15, 2016,
`received November 15, 2016, submitted pursuant to section 505(b)(2) of the Federal Food, Drug,
`and Cosmetic Act (FDCA) for BendekaTM (bendamustine hydrochloride) Parenteral 100 mg/4mL
`(25mg/mL).
`
`This “Prior Approval” supplemental new drug application proposes the following change(s):
`Increase the long term stability limit for the
`(b)(4)
`“9 (4) impurity from NMT (”Wm NMT (”min the drug product specifications.
`
`We have completed our review of this supplemental new drug application. This supplement is
`approved.
`
`We remind you that you must comply with the requirements for an approved NDA set forth
`under 21 CFR 314.80 and 314.81.
`
`If you have any questions, call Rabiya Laiq, Pharm.D., Regulatory Business Process Manager, at
`(240) 402-6153.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Anamitro Banerjee, Ph.D.
`Branch Chief, Branch II (Acting)
`Office of New Drug Products
`Office of Pharmaceutical Quality
`Center for Drug Evaluation and Research
`
`
`
`Anamitro
`
`Baneuee
`
`
`
`
`
`Digitally signed by Anamitro Banerjee
`Date: 2/06/2017 07:57:58PM
`GUID: 5075764700003844b7bc89632228509f
`
`
ÿ
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`
` ÿÿ
`
` ÿ!"!!#$"$%
`
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`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`
`
`
`APPLICATION NUMBER:
`NDA 208194/S-004
`NDA 208194/S-004
`
`
`APPLICA TION NUMBER:
`
`
`
`
`
`
`
`CHEMISTRY REVIEWS
`CHEMISTRY REVIEWS
`
`
`
`
`2. NDA NUMBER Original
`
`N 208194
`
`RESUBMISSION
`
`E1:1
`
`4. SUPPLEMENT(S)
`NUMBER S
`
`S-004
`5. DATE S
`Submit Date
`
`FDA Receipt Date
`Goal Date
`
`Chemist Receipt Date
`Amendments
`
`TYPE
`
`PAS
`
`November 14. 2016
`
`November 15. 2016
`March 14, 2017
`
`November 17, 2016
`
`Date Completed
`7. NAME OF THE DRUG
`
`January 6, 2017
`
`Bendamustine h drochloride
`
`I CIIEMIST‘S REVIEW #1
`
`l. ORGANIZATION
`
`ONDP
`
`3. NAME AND ADDRESS OF APPLICANT
`
`Company Name:
`Street Address:
`
`Eagle Pharmaceuticals, Inc.
`50 Tice Boulevard
`Suite 315
`
`City:
`State:
`
`Zip Code:
`Country:
`
`Woodcliff Lake
`NJ
`
`07677
`USA
`
`6. PROPRIETARY NAME
`
`BENDEKATM ln'ection
`8. SUPPLEMENT PROVIDES FOR:
`
`thfilong term stability limit for the
`lncreas
`NMT H in the dru roduct s-ecifications.
`9. INDICATION
`
`treatment of chronic] mohoc tic leukemia
`12. DOSAGE FORM
`IV
`
`
`
`4-(S-(bis(2-chloroethyl)amino)-1 -methyl-| H~benzo[d]imidazo1-2-y1)butanoic
`hydrochloride
`
`4-(5-(bis(2-chloroethyl)amino)-1methyl-1H—benzo[d]imidazol-Z-yl)butanoic
`acid hydrochloride
`Chemical Formula: C16H22C|3N302
`Molecular Weight; 394.72
`
`16. COMMENTS
`(b) (”impurity in the drug product specifications for
`The applicant is proposing to increase the limit for the
`stability to NMT I”) (”based on data from seven commercial scale batches. The applicant further argues. based on literature
`reports that
`(b) “’of bendamustine. Further. the applicant provided analysis of
`commercially available bendamustine (TREANDA‘, the listed drug) through the shelf life in support of the proposed 5
`cifications
`for this impurity. The non-clinical reviewer Dr. Michael Manning indicated that the proposed specification of NMT 6’ (”is
`acceptable from the Pharm/Tox perspective.
`The information provided in this submission was found to be adequate to support the proposed change.
`
`1585 Status: N. A.
`
`18. REVIEWERS SIGNATURE
`
`REVIEWER
`
`, manufacturin and controls.
`DIVISION DIRECTOR
`
`See a - ended electronic si _nature sheet
`
`Anamitro Baner'ee. PhD.
`
`Thomas Oliver, PhD.
`
`
`
`Review Notes
`
`NDA Number: N 208i 94
`S-004
`
`BENDEKAIR] (bendamustine hydrochloride) Injection for intravenous use was approved on December 07.
`
`2015 for the treatment ofpatients with chronic lymphocytic leukemia (CLL) and for patients with indolent
`
`B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with
`
`rituximab or a rituximab containing regimen.
`
`Proposed changes
`
`Increase the long term stability limit/hr the
`
`(”(4)
`
`impuritvfrom NMT (b) (”to NMT (h) min the drug product specifications.
`
`Justification: Based on additional stability data available for seven commercial scale batches ofthe drug
`
`product.
`
`Summary
`
`mmimpurity in the drug product
`The applicant is proposing to increase the limit for the
`4
`specifications for stability to NMT (bu )based on data from 7 commercial scale batches. The applicant
`further argues, based on literature reports that
`MWof
`
`bendamustine. Further, the applicant provided analysis of commercially available bendamustine
`
`(TREANDAR‘, the listed drug) through the shelf life in support of the proposed specifications for this
`
`impurity.
`
`H0
`
`O
`
`in
`W tr
`N\
`Monochloroeihyl bendamustine (MCE)
`Chemical Formula: CHH|9C|3N302
`Molecular Weight: 332.23
`
`In support of the proposed change in the specifications for
`
`M“), the applicant indicated
`
`that additional data from commercial batches, data from the listed drug TREANDAQQ, and literature reports
`
`justify the proposed change and adequately establish the safety of this impurity. The information provided
`
`by the applicant is summarized below:
`
`Following this page, 2 pages withheld in full - (b)(4)
`
`2
`
`
`
`
`
`Banen'ee, Anamitro
`
`From:
`Sent:
`To:
`Cc:
`
`Subject:
`
`Hi Anamitro,
`
`Manning, Michael
`Thursday, December 22, 2016 1:51 PM
`Banerjee, Anamitro
`Sheth, Christopher
`
`RE: Consult needed. PAS supplement. NDA 208194—004
`
`is acceptable from the pharm/tox perspective. The
`
`
`The proposed specification limit of
`rationale is tha
`
`
`
`f the total bendamustine dose.
`
`
`
`Thanks,
`
`Michael
`
`From: Banerjee, Anamitro
`Sent: Tuesday, December 20, 2016 10:17 AM
`To: Laiq, Rabiya
`Cc: Manning, Michael; Sheth, Christopher
`Subject: RE: Consult needed. PAS supplement. NDA 208194-004
`
`Thanks Rabiya.
`
`Hi Michael,
`The applicant is proposing to change the specifications for the impurity—
`from NMT -to -based on additional stability data. The applicant has provided an assessment
`exposure in cancer patients. Please let me know if the proposed specification is acceptable from PT
`
`report on
`perspective.
`Thanks
`Anamitro
`
`
`
`Digitally signed by Anamilro Banerjee
`Date: 1/06/2017 11:07:00PM
`GUID: 5075764700003844b7bc89632228509f
`
`
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`Digitally signed by Thomas Oliver
`Date: 1/08/2017 01:52:36PM
`
`GUID: 508da71f00029ed46977000ee3d31ca0
`
`Anamltro
`
`Baneuee
`
`
`
`
`&'
`( )
`
`
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`
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`
`Digitally signed by Thomas Oliver
`Date: 1/08/2017 01:52:36PM
`
`GUID: 508da71f00029ed46977000ee3d31ca0
`
`Anamltro
`
`Baneuee
`
`
`
`
`&'
`( )
`
`
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