1. Inspection Readiness at a Start-up: Case Study
Donna W. Dorozinsky
President & CEO
Just in Time GCP

2. Situation - December Team Small Start up 3 Studies
1 Regulatory
4 Clinical
1 Medical Officer
3 Studies
NDA planned for March
Get us Inspection Ready
Situation - December

3. Protocol #1 Pivotal trial with DBL planned for end of January
Change in CRO with migration of database (CRO A)
Subsequently 2 CROs due to delayed enrollment
CRO B – US sites and RoW, biometrics
CRO C – US sites
TMF
TMF from original CRO with sponsor on CDs
Both add on CROs holding their TMF Content in eTMF
1200 documents between the 2 TMFs
Sponsor held some TMF content on shared drives, s, etc
Vendor content held by vendors
ePRO used for primary endpoint
Issue with configuration for eligibility requiring manual calculation of eligibility for a period of time

4. Protocol #2 Pivotal trial with database locked in October of that year
2 CRO
CRO B – US sites and RoW, biometrics
CRO C – US sites
TMF
Both CROs holding their TMF Content in eTMF
1800 documents between the 2 TMFs
Sponsor held some TMF content on shared drives, s, etc
Vendor content held by vendors

5. Protocol #3 Open Label Extension
Not all subjects rolled from #1 & #2 protocols
Study was active and would be active at time of NDA filing
Only CRO C for this study, added biometrics responsibilities
Sponsor held some TMF content on shared drives, s, etc
TMF
CRO holding their TMF Content in eTMF
600 documents between the 2 TMFs
Vendor content held by vendors

6. Identifying Risks 3 studies with large gaps in TMF Content
Change in CRO & subsequent database transfer
General CRO oversight – TMF oversight gaps
Sponsor Content
Identifying Risks

7. Overall Strategy Focus on anticipated BIMO Activities
Understand the Story
Make sure the TMF tells the Story
Engage CRO as partners in remediation
Continue to have CROs hold TMF for inspection

8. Prioritization Remediate TMFs Storyboards Change in CROs
Database Transfer
CRO Oversight
Sight Selection
ePRO issues
TMF Oversight

9. TMF Remediation Completeness of CRO TMFs
Data Integrity of Transferred TMF Content
Completeness and security of sponsor content
TMF Remediation

10. CRO Completeness Met with each CRO to discuss TMF Gaps
Developed Inspection Readiness Plan for each CRO
Weekly meetings with CRO to track progress
Identified high level gaps – essential documents
Protocol training
CoV document for both protocol #1 & #2
Monitoring Visit documents
CROs had 60 days to clean up TMF
As CROs reported a site’s file as complete, sponsor performed completeness review and issued queries – immediately identified trend in gaps
Continued weekly meetings until fully remediated
Established TMF Map to identify content location

11. Sponsor Content – CD from CRO & Sponsor Generated
Implemented sponsor eTMF
Met with 2 vendors
Implemented selected vendors standard configuration with minor changes
Developed Change Management SOP to govern implementation
Implementation took 12 weeks
Upload all sponsor content to eTMF
High number of documents related to the changes in CRO and transfer of database
Sponsor Content – CD from CRO & Sponsor Generated

12. Storyboards
During period of time that CROs were collecting gap content, worked to establish storyboards to help identify sponsor content
Searched s of 4 team members and one individual who had left during the study
Reconstructed key events with documentation we found
Utilized pseudo “risk tracker” that study lead had maintained.

13. Outcome
Inspection in September with over 40,000 documents between the 3 TMFs
Inspector wanted paper
Full remediation following inspection

14. Thank you! Donna Dorozinsky ddorozinsky@justintimegcp.com
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