206316Orig1Orig2s000...Drug: Edoxaban Tablets, 15 mg, 30 mg and 60 mg Subject OCrecommendation...
Transcript of 206316Orig1Orig2s000...Drug: Edoxaban Tablets, 15 mg, 30 mg and 60 mg Subject OCrecommendation...
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CENTER FOR DRUG EVALUATION AND RESEARCH
APPLICATION NUMBER:
206316Orig1Orig2s000
CHEMISTRY REVIEW(S)
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DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug AdministrationSilver Spring, MD 20993
CMC Memo to File
To: NDA 206316Date 15 December 2014
Sponsor: Daiichi-SankyoDrug: Edoxaban Tablets, 15 mg, 30 mg and 60 mg
Subject OC recommendationReviewer Dr. Akm Khairuzzaman
Pursuant the overall “acceptable” recommendation given on 14-Nov-2014 for the manufacturing facilities by the Office of Compliance, the CMC recommendation is no changed to “Recommended for Approval” from CMC perspective.
HFD-/Division FileHFD-120
Akm Khairuzzaman, Ph.D.Chemistry Reviewer
Olen Stephens, Ph.D.Acting Branch Chief, ONDQA
Reference ID: 3672974
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AKM KHAIRUZZAMAN12/15/2014Recommended for Approval from CMC point of view
OLEN M STEPHENS12/15/2014
Reference ID: 3672974
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Savaysa (edoxaban) tablets
NDA 206316
Summary Basis for Recommended Action
from Chemistry, Manufacturing, and Controls
Applicant: Daichii Sankyo.US Agent: Doreen V. Morgan399 Thornall Street, 10th FloorEdisonNJ 08837
Indication: To reduce the risk of stroke and systemic embolism inpatients with nonvalvular atrial fibrillation (DCRP)
Treatment of deep vein thrombosis and pulmonaryembolism (DHP)
Presentation: The product will be available in 15 mg, 30 mg, and 60 mg strength,immediate release, film coated tablets. The tablets are orange, round-shaped, debossed with “DSC L15” (15 mg tablets), pink, round shaped, debossed with “DSC L30” (30 mg), and yellow, round shaped, debossed with “DSC L60” (60 mg tablets). The tablets are packaged in HDPE bottles with 7, 30, 90 and 500 counts. The tablets are also available in
aluminum foil blister unit dose packages of 7 and 10 counts.
EER Status: Overall recommendation is pending as of 2-Oct-2014.
Consults: ONDQA Biopharmaceutics - Acceptable with PMC (Sandra Suarez, 9-Sep-2014).
Microbiology - Acceptable (Steven Donald, 3-Apr-2014)
Methods Validation - Acceptable (Jason Rodriguez, 5-Sep-14)
EA – Categorical exclusion granted.
Reference ID: 3640230
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3
All associated Drug Master Files are acceptable or the pertinent information has been adequately provided in the application.
Overall Conclusion: The application is recommended for “Approval” from CMC perspective pending a final overall “Acceptable” recommendation from the Office of Compliance about the manufacturing facilities.
Ramesh K. Sood, Ph.D.Acting Director, DPA I/ONDQA
Reference ID: 3640230
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RAMESH K SOOD10/07/2014
Reference ID: 3640230
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Memorandum DEPARTMENT OF HEALTH AND HUMAN SERVICESPUBLIC HEALTH SERVICEFOOD AND DRUG ADMINISTRATIONCENTER FOR DRUG EVALUATION AND RESEARCH
Date: 21-Aug-2014
From: Janice Brown, M.S.CMC LeadDNDQA I/ONDQA
Through: Ali Al-Hakim, Ph.D.Chief, Branch IINew Drug Quality Assessment Division I1ONDQA
To: NDA 206316Edoxaban Tablets
Subject: Risk Assessment
As per a new policy, each NDA with GRMP dates on or after August 1, 2014 will include a risk assessment in the Executive summary. This will be based on an initial risk assessment that would be captured in all IQAs written for NDAs received on or after June 1, 2014. It was decided that the CMC Lead would perform a retrospective risk assessment for those NDAs received prior to June 1, 2014 that had GRMP dates after August 1, 2014.
The following IQA template was provided:
In an email dated 30-May-2014, Dr. Ramesh Sood provided follow-up guidance on how to fill out the required IQA template that is used to populate the NDA template. The guidance provided templates for the most common dosage forms.
Reference ID: 3614785
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JANICE T BROWN08/22/2014
ALI H AL HAKIM08/22/2014
Reference ID: 3614785
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AKM KHAIRUZZAMAN09/08/2014
DEBASIS GHOSH09/08/2014Responsible for Drug Substance Review only
YUBING TANG09/08/2014
SHARMISTA CHATTERJEE09/08/2014
OLEN M STEPHENS09/08/2014
Reference ID: 3623807
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MICHAEL L TREHY09/05/2014
Reference ID: 3622844
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DPATR-FY14-055 Page 1 of 5 Version: 2/6/2013
DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service
Food and Drug Administration Center for Drug Evaluation and Research
METHODS VALIDATION REPORT SUMMARY
TO: Akm Khairazzuman and Debasis Ghosh, CMC Reviewer
Office of New Drug Quality Assessment (ONDQA) E-mail Address: [email protected] Phone: (301)-796-3886 (Akm); (301) 796-4093 (Debasis) Fax: (301)-796-9747
FROM: FDA Division of Pharmaceutical Analysis
Michael Trehy, MVP Coordinator 645 S Newstead Avenue
St. Louis, MO 63110 Phone: (314) 539-3815 Through: John Kauffman, Deputy Director Phone: (314) 539-2168 SUBJECT: Methods Validation Report Summary
Application Number: 206316 Name of Product: Savaysa (edoxaban), Tablets 15, 30 amd 60 mg
Applicant: Daiichi Sankyo, Inc.
Applicant’s Contact Person: Doreen V. Morgan, Pharm.D.; Executive Director, Regulatory Affairs
Address: 399 Thornall Street, 10th floor, Edison, NJ 08837 Telephone: (732) 590-5198 Fax: (732) 906-5562 Date Methods Validation Consult Request Form Received by DPA: Feb-28-2014
Date Methods Validation Package Received by DPA: Feb-28-2014
Date Samples Received by DPA: Apr-15-2014
Date Analytical Completed by DPA: June-24-2014
Laboratory Classification: 1. Methods are acceptable for control and regulatory purposes.
2. Methods are acceptable with modifications (as stated in accompanying report).
3. Methods are unacceptable for regulatory purposes.
Comments: See attached memo for analysts’ comments and data summary.
Reference ID: 3531225
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DPATR-FY14-055 Page 3 of 5 Version: 2/6/2013
DPA has the following comments pertaining to the following methods.
(Daiichi Sankyo, Inc, 3.2.P.5.2)
Reference ID: 3531225
(b) (4)
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MICHAEL L TREHY06/24/2014
JOHN F KAUFFMAN06/25/2014
Reference ID: 3531225
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EDOXABAN TOSYLATE / N 206-316
INSPECTIONAL ASSIGNMENT (EMAIL TRANSMITTAL)
Date: May 23, 2014 To: International
Division of Medical Products and Tobacco Inspections Office of Regulatory Affairs
Facility(ies): Daiichi Sankyo Propharma Co., Ltd. (DSPP)
Akita Plant, 1-10-1, Mukaihama, Akita-shi Akita, 010-1601, Japan FEI No: 3002806777 and Daiichi Sankyo Chemical Pharma Co., Ltd. (DSCP) Odawara Plant, 477, Takata, Odawara-shi, Kanagawa 250-0216, Japan FEI No.: 3003279188
Drug Name (dosage form, strength/concentration):
Edoxaban Tosylate Drug Substance
Profile Class: A/NDA No.: NDA 206-316 Chemistry Reviewer Debasis Ghosh, Ph.D.
CDER/OPS/ONDQA/DNDQAI/BRII [email protected] Tel: 310-796-4093
Microbiology Reviewer (if applicable)
N/A
OC Compliance Officer
Vipul Dholakia, Ph.D, CDER/OC/OMPQ HFD-320 [email protected] Tel. 301-796-5065
CDER has identified specific area(s) for inspectional focus for drug substance manufacturing in connection with the NDA 206-316. In accordance with the API Process Inspection Compliance Program 7356.002F, PAIs provide for continuity in our pre-market review of drug product by focusing on areas in which data is questionable; drug
Reference ID: 3512233
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EDOXABAN TOSYLATE / N 206-316
The following is a brief explanation of product or process specific issues that should receive follow-up during the inspection. I. Chemistry Review The chemistry reviewer, Debasis Ghosh did not have any major issue for inspectional coverage.
II. Microbiology Review The microbiology reviewer, Steven Donald did not have any major issue for inspectional coverage. III. Manufacturing Edoxaban Tosylate (Daiichi Sankyo Propharma Co. Ltd.)
a.
b.
c.
Reference ID: 3512233
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EDOXABAN TOSYLATE / N 206-316
ii.
e. Distribution Supply Chain:
i.
A pre-inspection briefing may be scheduled if additional clarification or background is needed. Should you have questions prior to or post inspection or for significant deficiencies observed during inspection, please contact the CDER officials identified above. Please report your findings regarding these issues in the Establishment Inspection Report (EIR) under the heading, “ADDITIONAL INFORMATION” with the subheading, “Follow-up to CDER Questions.”
Reference ID: 3512233
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VIPULCHANDRA N DHOLAKIA05/23/2014
MAHESH R RAMANADHAM05/23/2014
Reference ID: 3512233
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---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------
VIBHAKAR J SHAH03/05/2014
VIPULCHANDRA N DHOLAKIA03/05/2014
MAHESH R RAMANADHAM03/05/2014
Reference ID: 3465358
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Page 1 of 4 Version: 02/06/2013
DEPARTMENT OF HEALTH AND HUMAN SERVICESPublic Health Service
Food and Drug AdministrationCenter for Drug Evaluation and Research
METHODS VALIDATION CONSULT REQUEST FORM
TO: FDADivision of Pharmaceutical AnalysisAttn: Michael TrehySuite 10021114 Market StreetSt. Louis, MO 63101
FROM: Akm Khairazzuman and Debasis Ghosh, CMC Reviewers Kasturi Srinivasachar, CMC Lead
Office of New Drug Quality Assessment (ONDQA)E-mail Address: [email protected]; [email protected]: (301)-796 3886 (Akm); (301)-796 4093 (Debasis)Fax.: (301)-796 9747
Through: Olen Stephens, Acting Branch Chief Phone: (301)-796 3901
andYoubang Liu, ONDQA Methods Validation Project ManagerPhone: (301)-796 1926
SUBJECT: Methods Validation Request
Application Number: NDA 206316
Name of Product: Savaysa (edoxaban), Tablets, 15, 30 and 60 mg
Applicant: Daiichi Sankyo, Inc.
Applicant’s Contact Person: Doreen V. Morgan, Pharm.D., Executive Director, Regulatory Affairs
Address: 399 Thornall Street, 10th
floor, Edison, NJ 08837
Telephone: 732-590-5198 Fax: 732-906-5562
Date NDA Received by CDER: 1-8-14 Submission Classification/Chemical Class: NME
Date of Amendment(s) containing the MVP: 1-8-14 Special Handling Required: No
DATE of Request: 2-28-14 DEA Class: N/A
Requested Completion Date: 5-28-14 Format of Methods Validation Package (MVP)
PDUFA User Fee Goal Date: 1-8-15 Paper X Electronic Mixed
We request suitability evaluation of the proposed manufacturing controls/analytical methods as descr bed in the subject application. Please submit a letter to the applicant requesting the samples identified in the attached Methods Validation Request. Upon receipt of the samples, perform the tests indicated in Item 3 of the attached Methods Validation Request as described in the NDA. We request your report to be submitted in DARRTS promptly upon completion, but no later than 45 days from date of receipt of the required samples, laboratory safety information, equipment, components, etc. We request that you notify the ONDQA Methods Validation Requestor and the ONDQA Methods Validation Project Manager of the date that the validation process begins. If the requested completion date cannot be met, please promptly notify the ONDQA Methods Validation Requestor and the ONDQA Methods Validation Project Manager.
Upon completion of the requested evaluation, please assemble the necessary documentation (i.e., original work sheets, spectra, graphs, curves, calculations, conclusions, and accompanying Methods Validation Report Summary). The Methods Validation Report Summary should include a statement of your conclusions as to the suitability of the proposed methodology for control and regulatory purposes and be electronically signed by the laboratory director or by someone designated by the director via DARRTS. The ONDQA CMC Reviewer, ONDQA Methods Validation Project Manager, and ONDQA CMC Lead/Branch Chief should be included as cc: recipients for this document.
All information relative to this application is to be held confidential as required by 21 CFR 314.430.
Reference ID: 3462850
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Page 4 of 4 Version: 02/06/2013
5
Novel or complex chromatographic methods (e.g., specialized columns/stationary phases, new detectors/instrument set-up, fingerprinting method(s) for a complex drug substance, uncommon chromatographic method
6Methods for which there are concerns with their adequacy (e.g., capability of resolving closely eluting peaks, limits of detection and/or quantitation)
7 Methods that are subject to a “for cause” reason
Reference ID: 3462850
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---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------
KASTURI SRINIVASACHAR02/28/2014
OLEN M STEPHENS02/28/2014
YOUBANG LIU02/28/2014
Reference ID: 3462850
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
Page 1 of 22
IQA and Filing Review Cover Sheet
1. NEW DRUG APPLICATION NUMBER: 206316
2. DATES AND GOALS:
Letter Date: Jan. 8, 2014
Submission Received Date :Jan. 8, 2014
PDUFA Goal Date: Jan. 8, 2015
3. PRODUCT PROPERTIES:
Trade or Proprietary Name: Savaysa (proposed)Established or Non-Proprietary Name (USAN):
Edoxaban
Dosage Form: Tablets, immediate releaseRoute of Administration OralStrength/Potency 15, 30 and 60 mg
Rx/OTC Dispensed: Rx
4. INDICATION: 1) To reduce the risk of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation; 2) for the treatment of venous
thromboembolism including DVT and PE;
5. DRUG SUBSTANCE STRUCTURAL FORMULA:
6. NAME OF APPLICANT (as indicated on Form 356h):
Daiichi Sankyo, Inc.
Reference ID: 3459732
(b) (4)
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
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7. SUBMISSION PROPERTIES:
Review Priority: Standard
Submission Classification (Chemical Classification Code):
Type 1, NME
Application Type: 505(b)(1)
Breakthrough Therapy No
Responsible Organization(Clinical Division):
Division of Cardiovascular and Renal Products and Division of Hematology Products
8. CONSULTS:
CONSULT YES NO COMMENTS: (list date of request if already sent)Biometrics XClinical Pharmacology XEstablishment Evaluation Request (EER)
X
Pharmacology/Toxicology X If needed by reviewer for genotoxic impuritiesMethods Validation XEnvironmental Assessment XCDRH XOther X Microbiology
Reference ID: 3459732
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
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5. Thepost-approvalandannualstabilityprotocolsandtheiracceptancecriteriaareacceptable,fromamicrobiologicalstandpoint.
Reference ID: 3459732
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
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Parameter Yes No Comment
7.
Are drug substance manufacturing sites identified on FDA Form 356h or associated continuation sheet? For each site, does the application list: Name of facility, Full address of facility including
street, city, state, country FEI number for facility (if previously
registered with FDA) Full name and title, telephone, fax
number and email for on-site contact person.
Is the manufacturing responsibility and function identified for each facility?, and
DMF number (if applicable)
X
8.
Are drug product manufacturing sites identified on FDA Form 356h or associated continuation sheet. For each site, does the application list: Name of facility, Full address of facility including
street, city, state, country FEI number for facility (if previously
registered with FDA) Full name and title, telephone, fax
number and email for on-site contact person.
Is the manufacturing responsibility and function identified for each facility?, and
DMF number (if applicable)
X
Reference ID: 3459732
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
Page 21 of 22
49.
If the NDA is not fileable from the product quality perspective, state the reasons and provide filing comments to be sent to the Applicant.
N/A (fileable)
50.
If the NDA is not fileable from the biopharmaceutics perspective, state the reasons and provide filing comments to be sent to the Applicant.
N/A (fileable)
51.Are there any potential review issues identified?
The dissolution acceptance criterion is not supported by the data (requesting additional information)
The discriminating ability of the dissolution method is uncertain (requesting additional information)
The steps for the dissolution model did not include data to demonstrate the ability of the model to
(requesting additional data). Need additional data to support the
approval of the 15 mg strength
52.Are there any filing comments to be conveyed to the Applicant?
See Biopharmaceutics comments in page12.
53.Are there any comments to be conveyed to other review disciplines?
Comments Conveyed to the OCP Review Team on 02/20/14: There were major changes implemented to the drug product tested in Phase 1 and Phase 2 studies that may require additional data to support the bridging. The need for these data will be determined by the impact/relevance of the PK studies conducted in early phases of the development to the product labeling.
Reference ID: 3459732
(b) (4)
(b) (4)
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ONDQA Initial Quality Assessment (IQA) and Filing Review For Pre-Marking Applications
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This document will be sequentially signed in DARRTS by all of the following who authored or reviewed this assessment:
See appended electronic signature page}
Kasturi Srinivasachar, Ph.DCMC-Lead or Division I, Branch 1Office of New Drug Quality Assessment
{See appended electronic signature page}
Sandra Suarez, Ph.D.Biopharmaceutics ReviewerOffice of New Drug Quality Assessment
{See appended electronic signature page}
Angelica Dorantes, Ph.D.Biopharmaceutics Team LeaderOffice of New Drug Quality Assessment
{See appended electronic signature page}
Olen Stephens, Ph.D.Acting Branch Chief Division I, Branch 1Office of New Drug Quality Assessment
Reference ID: 3459732
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---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------
KASTURI SRINIVASACHAR02/24/2014
SANDRA SUAREZ02/24/2014
ANGELICA DORANTES02/24/2014
OLEN M STEPHENS02/24/2014
Reference ID: 3459732