CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`NDA 202155/ S-13
`
`Trade Name:
`
`ELIQUIS
`
`Generic Name: Apixaban
`
`Sponsor:
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`Bristol Myers Squibb
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`Approval Date: 05/03/2016
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`Indications: ELIQUIS is a factor Xa inhibitor indicated:
`• to reduce the risk of stroke and systemic embolism in patients
`with non-valvular atrial fibrillation.
`• for the prophylaxis of deep vein thrombosis (DVT), which may
`lead to pulmonary embolism (PE), in patients who have
`undergone hip or knee replacement surgery.
`• for the treatment of DVT and PE, and for the reduction in the
`risk of recurrent DVT and PE following initial therapy.
`
`
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`NDA 202155/ S-13
`
`Trade Name:
`
`ELIQUIS
`
`Generic Name: Apixaban
`
`Sponsor:
`
`Bristol Myers Squibb
`
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`Approval Date: 05/03/2016
`
`
`
`
`Indications: ELIQUIS is a factor Xa inhibitor indicated:
`• to reduce the risk of stroke and systemic embolism in patients
`with non-valvular atrial fibrillation.
`• for the prophylaxis of deep vein thrombosis (DVT), which may
`lead to pulmonary embolism (PE), in patients who have
`undergone hip or knee replacement surgery.
`• for the treatment of DVT and PE, and for the reduction in the
`risk of recurrent DVT and PE following initial therapy.
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`NDA 202155/ S-13
`
`CONTENTS
`
`
`Reviews / Information Included in this NDA Review.
`
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`X
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`
`
`
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`X
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`
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`X
`
`
`Approval Letter
`Other Action Letters
`Labeling
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Other Review(s)
`Administrative/Correspondence Document(s)
`
`
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`
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`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 202155/ S-13
`NDA 202155/ S-13
`
`APPLICA TION NUMBER:
`
`APPROVAL LETTER
`
`APPROVAL LETTER
`
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`
`NDA 202155/S-013
`
`
`APPROVAL LETTER
`
`Bristol-Myers Squibb Company
`Attention: Diptee Gajjar, B.Pharm, Ph.D.
`Director, Global Regulatory Lead, Global Regulatory & Safety Sciences
`P.O.Box 4000
`Princeton, NJ 08543-4000
`
`
`Dear Dr. Gajjar:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received November
`30, 2015, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for Eliquis (apixaban) 2.5 mg and 5 mg Tablets.
`
`This “Changes Being Effected in 30 days” supplemental new drug application provides to add
`Bristol-Myers Squibb’s facility in Humacao, Puerto Rico as a Packaging Site for apixaban
`Tablets.
`
`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 Maryam Changi, Regulatory Business Process Manager, at (240)
`402-2725.
`
`
`
`Digitally signed by Wendy I. Wilson -S
`DN: c=US, o=U.S. Government, ou=HHS, ou=FDA,
`ou=People, 0.9.2342.19200300.100.1.1=1300396790,
`cn=Wendy I. Wilson -S
`Date: 2016.05.03 09:29:27 -04'00'
`
`Sincerely,
`
`Wendy I. Wilson -S
`
`
`Wendy Wilson-Lee, Ph.D.
`Branch Chief, Branch 1 (Acting)
`Division of New Drug Product 1
`Office of Pharmaceutical Quality
`Center for Drug Evaluation and Research
`
`
`
`
`
`CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 202155/ S-13
`NDA 202155/ S-13
`
`APPLICA TION NUMBER:
`
`CHEMISTRY REVIEW(S)
`CHEMISTRY REVIEW! S!
`
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`DIVISION OF NEW DRUG PRODUCTS I
`NDA 202155, S-013
`REVIEW OF CHEMISTRY, MANUFACTURING, AND CONTROLS
`
`NDA #: 202155
`
`DATE REVIEWED: 05/02/16
`
`OND: Division of Cardiovascular and Renal Drug Product
`
`REVIEW #: 1
`
`REVIEWER: Sherita McLamore-Hines, Ph.D.
`
`SUBMISSION TYPE:
`CBE-30 Supplement
`
`CDER DATE:
`12/18/2015
`
`NAME & ADDRESS OF APPLICANT:
`Applicant: Bristol-Myers Squibb (BMS)
`
`
`P.O. Box 4000
`
`
`Princeton, NJ 08543
`
`Representative: n/a
`
`DRUG PRODUCT NAME:
`Proprietary: ELIQUS™
`Established: apixaban
`
`PHARMACOL. CATEGORY/INDICATION: Treatment of Acute Coronary Syndrome (ACS)
`
`DOSAGE FORM: Film Coated Tablets
`
`STRENGTHS: 2.5 mg and 5 mg
`
`ROUTE OF ADMINISTRATION: Oral
`
`Rx/OTC: Rx
`
`____Yes xx No
`
`SPECIAL PRODUCTS:
`
`CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR FORMULA, MOLECULAR
`WEIGHT:
`Chemical Name: 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperdinyl)phenyl], 4,5,6,7-
`tetrahydro-1H-Pyrazolo[3,4-c]pyridine-3-carboxamide
`
`Molecular Formula: C25H25N5O4
`MW: 459.50
`Chemical Structure:
`
`
`
`
`
`
`
`n/a
`
`SUPPLEMENT PROVIDES FOR: ELIQUIS™ (apixaban) 2.5 and 5 mg film coated tablets are
`currently manufactured and released tested by BMS of Humacao, PR and BMS of Mt. Vernon, IN.
`The approved packaging sites are BMS of Mt. Vernon (blisters and bottles), BMS of Frosinone, Italy
`(blisters and bottles) and
`. This supplement provides for the
`addition of the BMS site in Humacao, PR as an additional packaging site for the drug product
`(bottles only). There are no other changes are included in this supplement. No additional
`information is provided to support this change.
`
`CONSULT:
`
`SUPPORTIVE DOCUMENT: None
`
`CONCLUSION: While SUPAC-IR does not address the addition of a new packaging site, according
`to the FDA Guidance for Industry Container Closure Systems for Packaging Human Drugs and
`Biologics, Oral Tablets and Capsules are of low packaging concern as the likelihood of packaging
`components interacting with the packaging is low. Moreover, because the container closure system has
`proven to be suitable for the intended use and the proposed site is currently approved for
`manufacturing, packaging and testing the drug product, the reviewer is confident that the risks
`associated with the addition of the Humacao, PR as a drug product packaging site are insignificant.
`Accordingly, the applicant has provided adequate information to support the addition of BMS of
`Humacao, PR as an additional packaging site for ELIQUIS™ (apixaban) 2.5 and 5 mg film coated
`tablets. The applicant was asked to commit to placing one batch of each strength of the drug product
`packaged at the new site on stability. The applicant responded affirmatively and indicated that the
`results would be reported in the NDA annual report. Accordingly, we recommend that this application
`be APPROVED.
`
`(b) (4)
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`NDA 202155/ S-13
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`
`
`
`
`
`
`
`
`From:
`To:
`Subject:
`Date:
`Attachments:
`Importance:
`
`Kord Bacheh Changi, Maryam
`"diptee.gajjar@bms.com"
`CMC Information Request sNDA 202155/S-13
`Monday, April 25, 2016 4:21:00 PM
`image003.png
`High
`
`Dear Dr. Gajjar,
`
`We are reviewing the CMC portion of sNDA 202155/S-013 and have the following information
`requests:
`
`
`· Commit to placing one batch of each strength of the drug product packaged at the
`Humacao, PR site on stability. The stability results for the new packaging site are annual
`reportable.
`
`
`Please submit your response as an amendment to your application. Please also submit a copy to me
`via email by April 29, 2016.
`Please kindly confirm the receipt of this email
`
`Thank you,
`
`Maryam Changi, PharmD,
`RBPM, Office of Program and Regulatory Operations (OPRO)
`Office of Pharmaceutical Quality/CDER/FDA
`Phone:(240) 402-2725
`Email: Maryam.Kordbachehchangi@fda.hhs.gov
`
`
`
`
`
`Kord Bacheh Changi, Maryam
`
`From:
`Sent:
`
`To:
`Subject
`
`Wilson, Wendy
`Wednesday, December 09, 2015 2:38 PM
`
`Kord Bacheh Changi, Maryam
`RE: Two new Supplement Triage form NDA 202155/S-013 and—
`
`0h, ok.
`
`I didn't catch that either.
`
`202155 can remain a CBE-30 if the site is in good standing. It is an immediate release product so it can be
`a CBE.
`
`Wendy
`
`From: Kord Bacheh Changi, Maryam
`Sent: Wednesday, December 09, 2015 2:27 PM
`To: Wilson, Wendy
`Subject: RE: Two new Supplement Triage form NDA 202155/5-013 and-
`
`Hi Wendy,
`
`202155/S-013 is a CBE-30...... I upgrade it to PAS
`
`I apologize, I think in my email below I miss- categorize them.
`
`Just confirm that above changes are ok!
`
`Maryam
`
`From: Wilson, Wendy
`Sent: Wednesday, December 09, 2015 2:19 PM
`To: Kord Bacheh Changi, Maryam
`Cc: Sapru, Mohan; McLamore—Hines, Sherita; Chelliah, Mariappan
`Subject: RE: Two new Supplement Triage form NDA 202155/5—013 and—
`
`Hi Maryam
`
`Sorry for the delay on these.
`
`202155/8-013 will remain a PAS and the assigned product quality reviewer will be Sherita will be the
`reviewer.
`
`
`
`Let me know if you need anything additional.
`
`
`
` Thanks.
`
`
`
`Wendy
`
`From: Kord Bacheh Changi, Maryam
`Sent: Wednesday, December 02, 2015 11:56 AM
`To: Wilson, Wendy
`Cc: Sapru, Mohan
`Subject: Two new Supplement Triage form NDA 202155/S-013 and
`
`Hi Wendy,
`
`Attached, please find two additional Supplements Triage forms for NDA 202155/S‐013 (PAS) and
` Please let me know when IQA is ready for them.
`
`
`
`
`Thanks,
`
`Maryam
`
`
`2
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`
`
`
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`
`
`NDA 202155/S-013
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`
`CBE SUPPLEMENT –
`ACKNOWLEDGEMENT
`
`202155
`
`S-013
`
`Eliquis (apixaban) Tablets
`
`
`Bristol-Myers Squibb Company
`Attention: Sekayi Mushonga, Pharm.D.
`Director, US Regulatory Liaison CV & Metabolics
`P.O. Box 4000
`Princeton, NJ 08543-4000
`
`
`Dear Dr. Mushonga:
`
`We have received your Supplemental New Drug Application (sNDA) submitted under section
`505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA or the Act) for the following:
`
`
`NDA NUMBER:
`
`SUPPLEMENT NUMBER:
`
`PRODUCT NAME:
`
`DATE OF SUBMISSION:
`
`DATE OF RECEIPT:
`
`This supplemental application, submitted as a “Changes Being Effected in 30 days” supplement,
`proposes the following change(s): Packaging site transfer from Mt Vernon to Humacao in Puerto
`Rico.
`
`Unless we notify you within 60 days of the receipt date that the application is not sufficiently
`complete to permit a substantive review, we will file the application on January 29, 2016 in
`accordance with 21 CFR 314.101(a).
`
`If the application is filed, the user fee goal date will be May 30, 2016.
`
`Cite the application number listed above at the top of the first page of all submissions to this
`application. Send all submissions, electronic or paper, including those sent by overnight mail or
`courier, to the following address:
`
`
`November 30, 2015
`
`November 30, 2015
`
`
`
`NDA 202155/S-013
`Page 2
`
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Cardiovascular and Renal Products
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`All regulatory documents submitted in paper should be three-hole punched on the left side of the
`page and bound. The left margin should be at least three-fourths of an inch to assure text is not
`obscured in the fastened area. Standard paper size (8-1/2 by 11 inches) should be used; however,
`it may occasionally be necessary to use individual pages larger than standard paper size.
`Non-standard, large pages should be folded and mounted to allow the page to be opened for
`review without disassembling the jacket and refolded without damage when the volume is
`shelved. Shipping unbound documents may result in the loss of portions of the submission or an
`unnecessary delay in processing which could have an adverse impact on the review of the
`submission. For additional information, see
`http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Drug
`MasterFilesDMFs/ucm073080.htm.
`
`If you have questions, call me, at (240) 402-2725
`
`
`Sincerely,
`
`
`
`
`Maryam Changi, Pharm.D
`Regulatory Business Process Manager
`Office of Program and Regulatory Operation
`Office of Product Quality
`Center for Drug Evaluation and Research
`
`
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