Presented on 25-Oct-2010

1. Quality Management of Safety
Data from Clinical Trials
Boris Videlov, MS, PMBA
Director PV QA
Forest Research Institute

2. 2
Disclosure
 This presentation is intended to be used
for informational purposes only
 The views expressed herein are those of
the author and do not necessarily
represent the views of Forest Research
Institute or any of its staff

3. 3
Main considerations
 Patient Safety
 Regulatory Compliance
but also
 Data Quality
 Trial Integrity

4. 4
Overview
 Essential processes
 Vendor Contracting Process
 Vendor GCP Monitoring Program
 Blinding/Unblinding Process
 Document Review Process
 Data Verification Process
 PV Monitoring Program
 Preparation for the Clinical Trial
 During the Clinical Trial
 PV Audit Management

5. Governed by Procedure(s) 5
Vendor Contracting Process
 Contractors – viewed by the authorities as extensions of
the company
 Transfer of obligations to a CRO (CFR 21 § 312.52)
 Joint effort between Clinical Development, Procurement,
Drug Safety, Product Development, Corporate Quality,
Marketing, Legal, and other departments
 Negotiate inter-departmental process
 Use of Contract Management System
 Requires subsequent Training and Monitoring
 Difficult to control affiliates’ contractual activities

6. Governed by Procedure(s) 6
Vendor Contracting Process
 Due Diligence Audit
 Safety Data (PV) Exchange / Quality Agreements
 Process for development and maintenance
 Consider using a safety agreements database (eg, Contract
Management tool)
 Maintain key responsibilities/timeframes reference document
and report(s)
 Include compliance clauses:
 Compliance with applicable regulations and agreements
 Response timeframes for compliance issues
 PV Audits
 Escalation of issues
 Penalties

7. Governed by Procedure(s) 7
Vendor GCP Monitoring Program
 Compliance Monitoring
 Site/data monitoring (CRFs to Drug Safety in timely manner if
found at site)
 Identify and address non-conformances
 Quality Monitoring
 Feedback from Clinical Development/Clinical Operations
 Identify and address trends
 Routine risk-based GCP auditing schedule
 For cause GCP site audit
 Documented CAPA
 Escalation to Procurement/Legal

8. Governed by Procedure(s) 8
PV Audit Management
 Classification
 Partner/CRO/Site Audits
 For cause/Routine
 Program/Trial
 Prioritization (risk-based)
 Tracking of findings/observations
 Observations
 Root Cause Type (high level)
 Tracking of commitments to address findings/
observations
 Trending
 Risk Management (ICH Q9)

9. Governed by Procedure(s) 9
Blinding/Unblinding Process
 Corporate-wide Blinding/Unblinding Procedure
 IVRS/IWRS system
 In house/Vendor selection
 System capabilities (company requirements)
 Controlled randomization data entry processes
 User maintenance and audit trail
 Unblinding for regulatory reporting purposes
 Contingency plans

10. 10
Document Review Process
 Shared company/departmental responsibility
 Routine and Ad hoc
 Document Types
 Internal Procedural Documents
 Investigator Brochure (updated)
 Clinical Trial Protocols/Amendments
 Informed Consent Form
 External Procedural Documents
 CRO documents
 Contractual
 S.O.W.
 SAE Monitoring Plan/AE Reporting Plan
 Safety Data Exchange Agreements
 Document and Contract Management Systems, integration
Governed by Procedure(s)

11. Governed by Procedure(s) 11
Data Verification Process
 Ensures the integrity and quality of the entire database
or data subset
 Full data verification vs. sample
 Routine
 Data verification between the Safety Database and the Clinical
Database
 Rationale
 Periodicity
 Key fields
 Ad hoc
 Database Upgrade/Migration
 Data(base) Transfer
 Data Cleansing
 Unblinding

12. Governed by Procedure(s) 12
PV Monitoring Program
-Preparation for the Clinical Trial
 Paper SAE Form vs. EDC
 CT Protocol review
 SAE and unblinding sections
 Forms customization
 SAE Form/Pregnancy Form/etc.
 Informed Consent Form review
 Site/Principal Investigator selection
 Coordinator and Investigator meetings
 Investigator Binder/CD preparation
 Training materials

13. Governed by Procedure(s) 13
PV Monitoring Program -
During the Clinical Trial
 Compliance Monitoring (metrics)
 Timeframes for SAE Form submission Investigator ⇨ (CRO) ⇨ Sponsor
(incoming) - Article 16 of Directive 2001/20/EC; 21 CFR § 312.64.
 Query response timeframes (incoming)
 Investigator/IRB/EC Notifications (outgoing) - Article 17 of Directive
2001/20/EC; 21 CFR § 312.32.
 Quality Monitoring (QA)
 SAE Form completeness and accuracy
 Query volume to sites and trends
 Discrepancies between Clinical Database and Drug Safety Database
 Documented CAPA – collaboration between Drug Safety, Corporate QA,
Clinical Development/Operations
 Official Notification/Memorandum
 Minuted teleconference
 F2F meeting
 Escalation to Corporate/Legal

14. Change Management
Planning for New Regulations
 Final Rule: IND Safety Reporting Requirements for
Human Drug and Biological Products and Safety
Reporting Requirements for BA and BE Studies in
Humans
 Revised definitions and new 15-day reporting requirement
 findings from clinical or epi studies that suggest a significant
risk to study subjects (and examples)
 SSARs that occur at a rate higher than expected
 SAEs from bioavailability studies (drug absorption rate by the
bloodstream and generic drug bioavailability)
 Draft: Guidance for Industry and Investigators: Safety
Reporting Requirements for INDs and BA/BE Studies
 effective date is March 28, 2011

15. 15
Thank you for your attention!
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