This document discusses quality management processes for safety data from clinical trials. It outlines key considerations like patient safety, regulatory compliance, and data quality. It then describes essential processes like vendor contracting, GCP monitoring of vendors, blinding/unblinding processes, document review, and data verification. It also discusses preparation for clinical trials, monitoring during trials, and PV audit management. Overall it provides an overview of quality processes to ensure integrity and compliance for safety data from clinical trials.

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

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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

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