Raising the Standard of Excellence Page 1 of 17 Preparing FDA Submission Data Packages Yuguang Zhao, MS Senior Vice President, Programming and Development Tiepu Liu, MD, PhD President of Global Biometrics
Raising the Standard of Excellence
Page 1 of 17
Preparing FDA Submission Data Packages
Yuguang Zhao, MS
Senior Vice President, Programming and Development
Tiepu Liu, MD, PhD
President of Global Biometrics
Raising the Standard of Excellence
Page 2 of 17
Contents
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............................................................................................................................................................................... 4
CDISC FDA: ............................................................................................................................................... 7
....................................................................................................................... 9
............................................................................................................................................. 11
SDSP - ............................................................................................................................... 11
................................................................................................................................................. 11
......................................................................................................................................................... 12
eCTD .................................................................................................................................................... 12
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............................................................................................................................................................................. 13
..................................................................................................................................................................... 14
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Raising the Standard of Excellence
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Food and Drug Administration : FDA 2016 12 17
New Drug Applications : NDAs
Biologics License Applications : BLAs Abbreviated New Drug Application :
ANDAs Standard for Exchange of Nonclinical Data : SEND
Study Data Tabulation Model : SDTM Analysis Data Model :
ADaM CDISC Clinical Data Interchange Standards Consortium
2017 12 17 INDs
1
FDA
FDA
2
CDISC FDA
FDA FDA
3
CDISC
FDA
FDA
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1998 4 FDA Center for Drug Evaluation and Research : CDER
Providing Regulatory Submissions in
Electronic Format-NDAs 4 1997 9
NDA
1998 FDA CBER
BLA PLA ELA
5
1999 FDA CDER CBER Guidance for Industry Providing Regulatory Submissions in Electronic
Format — General Considerations 6
NDA BLA
FDA
Common Technical Document CTD CTD International
Conference on Harmonization ICH 7 ICH CTD 5
1 1 2 5
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1 8
ICH
CTD
eCTD
CDISC
CDISC
CDISC
9
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2004 7 FDA eCTD CDISC
2006 12 CDISC SDTM
2015 5 FDA Providing Regulatory Submissions in Electronic Format – Certain Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (revision 3) 10
FDA NDA BLA
ICH FDA CDISC
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CDISC FDA:
FDA CDISC
CDISC
SDS – Submission Data Standards
ADaM – Analysis Data Model
SEND – Standard for Exchange of Non-clinical Data
CDASH – Clinical Data Acquisition Standards Harmonization
FDA
“The Food and Drug Administration Safety and Innovation Act” FDA
2012 7
”The Prescription Drug User Fee Act : PDUFA V”
5 CDISC
FDA PDUFA 11
2014 12 FDA “Providing Regulatory Submissions in Electronic Format — Standardized Study Data
12” 4 Data Standard Catalog
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FDA 13
Data Standards Catalog
Study Data Technical Conformance Guide
FDA Specific SEND Validation Rules
FDA Specific SDTM Validation Rules
Data Standards Catalog
FDA FDA
Study Data Technical Conformance Guide Study Data Specifications document CDER Common
Data Standards Issues document
NDA
BLA RTF Refuse-To-File ANDAs RRS Refuse-To-Receive
24 36
IND NDA ANDA BLA FDA
2016 12 17
2017 12 17 NDA / BLA ANDA
RTF RTR
FDA ICH eCTD CDISC FDA
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SEND SDTM
ADaM
:
SEND Data Package SDTM Data Package ADaM Data Package acrf.pdf .xpt files Define.xml Study Data Reviewer’s Guide (nSDRG.pdf)
acrf.pdf .xpt files Define.xml Study Data Reviewer’s Guide (cSDRG.pdf)
.xpt files Define.xml Analysis Data Reviewer’s Guide (ADRG.pdf)
Study Data Technical Conformance Guide 14
:
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SDSP -
2014 12 FDA Study Data Standardization Plan: SDSP
SDSP
SDSP
FDA
SDSP FDA
.
The Pharmaceutical Users Software Exchange (PhUSE)
SDSP 15 FDA
CSR
SDTM ADaM CSR
Integrated Summaries of Safety and Efficacy (ISS/ISE)
SDTM ADaM ISS/ISE SDTM
ADaM WHO drug MedDRA
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FDA FDA
pre-IND IND
CDER CBER FDA 16 NDA
II pre-
NDA / BLA
eCTD
FDA
FDA
RTF RTR
SDSP
FDA
FDA CDISC
/
CDISC
17
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CDISC
75 70-90
12 2
FDA
FDA
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1 Providing Regulatory Submissions in Electronic Format — Submissions Under Section 745A(a) of the Federal
Food, Drug, and Cosmetic Act, Guidance for Industry, U.S. Department of Health and Human Services Food and
Drug Administration Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and
Research (CBER), December 2014.
2 US FDA Website: http://www.fda.gov/AboutFDA/WhatWeDo/, FDA Mission, accessed January 18, 2017.
3 Providing Regulatory Submissions in Electronic Format — Standardized Study Data, Draft Guidance. U.S.
Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and
Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological
Health (CDRH), February 2012.
4 Guidance for Industry Providing Regulatory Submissions in Electronic Format — NDAs, Draft Guidance, U.S.
Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and
Research (CDER), April 1998
5 Electronic Submissions of a Biologics License Application (BLA), Product License Application (PLA)
/Establishment License Application (ELA) to the Center for Biologics Evaluation and Research (63 FR 29741,
6/1/98).
Electronic Submissions of Case Report Forms (CRFs), Case Report Tabulations(CRTs) and Data to the Center for
Biologics Evaluation and Research (63 FR 29739; 6/1/98).
Pilot Program for Electronic Investigational New Drug (eIND) Applications for Biological Products (63 FR 29740;
6/1/98).
Instructions for Submitting Electronic Lot Release Protocols to the Center for Biologics Evaluation and Research
(63 FR 29742; 6/98).
6 Guidance for Industry Providing Regulatory Submissions in Electronic Format — General Considerations, U.S.
Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and
Research (CDER), Center for Biologic Evaluation and Research (CBER), January 1999.
7 International Conference on Harmonization Website: http://www.ich.org/about/history.html, accessed,
January 18, 2017
8 International Conference on Harmonization Website: http://www.ich.org/products/ctd.html, accessed,
January 18, 2017.
9 Study Data Standards for Regulatory Submissions Position Statement, September 15, 2003, FDA Website:
http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/ucm368613.htm, Position Statement,
accessed January 18, 2017.
10 Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product
Applications and Related Submissions Using the eCTD Specifications Guidance for Industry, U.S. Department of
Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER),
Center for Biologics Evaluation and Research (CBER), May 2015, Electronic Submissions, Revision 3.
11 Study Data Standards for Regulatory Submissions Position Statement, September 15, 2003, FDA Website:
http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/ucm368613.htm, Position Statement,
accessed January 18, 2017.
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12 Providing Regulatory Submissions In Electronic Format — Standardized Study Data, Guidance for Industry,
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and
Research (CDER), Center for Biologics Evaluation and Research (CBER), December 2014, Electronic
Submissions.
13 Study Data Standards Resources, FDA Website:
http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm, Important Notices, accessed
January 18, 2017.
14 Study Data Technical Conformance Guide, Technical Specifications Document, U.S. Department of Health
and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), Center for
Biologics Evaluation and Research (CBER), November 2016.
15 Study Data Standardization Plan, PhUSE Website:
http://www.phusewiki.org/wiki/index.php?title=Study_Data_Standardization_Plan_(SDSP), Project
Deliverables, accessed January 18, 2017.
16 CDER/CBER Study Data Standardization Plan Recommendations, FDA Website:
http://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM447119.pdf, accessed
January 18, 2017.
17 2014 CDISC Business Case, Executive Summary, CDISC Website:
https://www.cdisc.org/system/files/all/article/PDF/2014%20Business%20Case_Executive%20Summary.pdf,
accessed January 18, 2017.
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Yuguang Zhao, MS
Senior Vice President of Programming and Development
Yuguang Zhao is the Senior Vice President of Programming and
Development at FMD K&L. Mr. Zhao is responsible for providing strategic
planning and corporate direction for continued growth of the company,
providing scientific leadership and resource planning for statistical support
on all projects, and ensuring the teams provide high quality statistical
programming support for Phase I, II, III, and IV clinical trials. He has over 19
years of experience in the pharmaceutical industry and has been very
active in industry working groups. He is used to be a member in the CDISC
SDS team and has received FDA Leveraging/Collaboration Award for the
participation of creation of SDTM and accompanying implementation guide
in 2005. He has co-led the CDISC/FDA data integration pilot. For questions
on preparing FDA Submission data packages, please contact Yuguang at:
Tiepu Liu, MD, PhD
President of Global Biometrics
Tiepu Liu, MD, PhD, is the President of Global Biometrics at FMD K&L. Dr.
Liu has served as Director of Biostatistics at PPD, Executive Director of
Statistics and Data Management at UBC, and a Senior Director of
Biostatistics at Graceway Pharmaceuticals and The Medicines Company,
before joining FMD K&L to lead the Biostatistics and Data Management
functions. Dr. Liu has published 100 scientific papers and more than 100
abstracts and presentations. He has served on numerous scientific review
committees and panels for the National Institute of Health (NIH) and other
government agencies. Dr. Liu has led numerous clinical development
projects, interacting with various regulatory agencies and Data Monitoring
Committees. He has been active in CDISC standards and CFAST initiative.
For questions on preparing FDA submission data packages, please contact
Tiepu at: [email protected].
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