As a niche provider, Vita Data Sciences has handled several Sponsor rescue case studies since our inception. In this slide share (presented at PhUSE SDE in Boston), we aim to provide background of our NDA submission experience and present a rescue case study where our team worked with a Sponsor towards their final NDA submission packet, even though the Sponsor had outsourced these services to a global full-service CRO. We have provided a brief background and outline significant gaps identified in the deliverables, services we offered, and summarize lessons learned/recommendations which can come in handy for anyone who is starting to work on their NDA clinical datasets package. Your feedback and comments are welcome.
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• Rescue Case Study Background
• Gap Assessment
• Remediation Performed
• Lesson Learned & Recommendations
Key Topics for Discussion
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4. www.vitadatasciences.com
• A mid-sized pharmaceutical company
• Sponsor’s first-ever NDA submission
• Limited in-house resources
• Outsourced to 3 different global CROs to work on their
late stage studies and submission support
• Six studies (Phases I-III) in both legacy and CDISC formats
Sponsor’s Background
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• CDISC SDTM format for all submitted studies
• Phase II-III analysis datasets in CDISC ADaM format
• ISS in CDISC ADaM format
• BIMO dataset and Site Level Subject Data Listings
• All datasets as per the Study Data Technical Conformance
Guide
Pre-NDA Meeting: FDA Expectations
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May June July Aug Sep Oct Nov Dec’15Jan’15 . . .
Feedback from the
FDA on test
submission (eData &
Reviewers)
Planned NDA
Submission
CRO 1 Contracted for
Legacy Mapping &
Submission Support
Revised NDA
Submission
Upon Feedback from
the FDA
Nov
NDA Submission Target at Risk
& Change Order $$$
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Inventory of Datasets CRT Submission Package
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Submission-Ready Deliverables Phase I Studies
(CRO 1)
Phase 2 Study
(CRO 2)
Phase 3 Studies
(CRO 3)
ISS
(CRO 3)
SDTM Datasets NA
SDTM aCRF X X NA
SDTM define X NA
SDTM reviewers guide X X X NA
ADaM/Legacy datasets
ADaM/Legacy define X
ADaM/Legacy reviewers
guide
X X X
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Case Report Form (CRF) was in word format
Different versions of OpenCDISC were used across all
studies.
SAS
®
codes were not provided to the Sponsor for the
FDA submission
BIMO datasets and site level subject data listings were
not programmed.
Gap Assessment – Miscellaneous
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May June July Aug Sep Oct Nov Dec’15Jan’15 . . .
Planned NDA
Submission
VDS Contracted
to Support NDA
Submission
10 Weeks
Submit Complete CRT
Package to Publishing
Vendor
Rescue Project Targeted Timeline
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• ‘Submission-ready’ CRT package in 10 weeks !
• Worked closely with the Sponsor and other CROs
• NDA submitted per original targeted timeline
• No feedback from the FDA on data compliance!
o Helped addressed questions from the FDA review division
• Provided support on several additional projects
Rescue Project – Successful!
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• Address OpenCDISC compliance issues during SDTM
dataset development
• Define.xml and SDTM aCRF developed early in the SDTM
development life cycle
• Ensure consistency used when multiple studies are
outsourced
• Reviewers guide should have details about your primary
efficacy end-points including reference to the SAS codes
Key Lessons Learned/Recommendation
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• Clear contract with added specifics about Sponsor
expectations for each deliverable
– Dataset standards and any Sponsor specific standards
– List of expected CDISC deliverables (XPTs, define, SDTM aCRF,
SDRG/ADRG)
– Number of Dry runs
– Compliance checks
– SAS Codes and associated macros
– ‘Submission-ready’ CRT package
• Sponsor’s oversight on outsourced deliverables
Key Lessons Learned/Recommendation
…contd (2)
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• Engage FDA review division early in the drug
development/submission process
– Study Data Standardization Plan (SDSP)
• Discuss datasets submission details at the pre-NDA
meeting
• Submit sample/test submission to the eData team and
FDA review division
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Key Lessons Learned/Recommendation
…contd (3)
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• Choose the right service provider/vendor to work on your
submission!
o Interview and qualify project team members
o Team members must have prior submission experience
o Data Standards and Submission SME should be part of the
team
Remember – goal must be to have ‘submission-ready’
deliverables from your vendor upfront!
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Key Lessons Learned/Recommendation
…contd (4)
A mid-sized pharmaceutical company (limited in-house resources)
Sponsor’s first-ever NDA Submission (Require access to functional expertise – CDISC data submission standards)
Six (Phases I-III) studies in both Legacy and CDISC formats previously assigned to two different large, global CROs (increased complexity)
To be submitted <12 weeks (Timeline!)
Incomplete SDTM Mapping Specifications
Missing SDTM aCRF or not per MSG guidelines, missing bookmarks
No define.xml or not validated through OpenCDISC; hyperlinks don’t function
Unresolved OpenCDISC validation compliance issues
No traceability report – legacy to SDTM
No reviewer’s guide or not used correct SDRG template
Missing define files for legacy analysis datasets
No ADaM define.xml or not validated through OpenCDISC; hyperlinks don’t function
Incomplete ADaM mapping specification/missing necessary components
Reviewer’s guide missing information on key efficacy endpoints.
