How Industry Can Partner with FDA in Defining a Risk- Based Monitoring Program Presenter: Jan Holladay Pierre, MPH Quality Principal Leader DynPort Vaccine Company LLC, A CSC Company This presentation is the property of DynPort Vaccine Company LLC, A CSC Company, and may not be reproduced without express written consent.
Defining a Risk-Based Monitoring Program Presenter: Jan Holladay Pierre, MPH Quality Principal Leader DynPort Vaccine Company LLC, A CSC Company
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Summing it Up Prior Presentations Described key aspects of the new guidance document on risk-based monitoring Identified the importance of risk-based monitoring from a regulatory perspective Discussed the practicalities of developing and executing a Risk-Based Monitoring Plan
Objectives Understand Monitoring Strategies Discuss a Site-Specific QC Checklist Describe Elements of a Risk-Based Monitoring Checklist 12
Monitoring Strategies Activity Pre-qualification of clinical sites Trial Master File (TMF) creation and maintenance Clinical supply management Monitoring Data listing review; CRF- SDV; source back to protocol requirements GCP compliance Description Identify disparate points of entry for source document verification (SDV) verify adequately experienced staff to include ancillary roles and assure workload is appropriate (i.e., request active protocols). TMF assists sponsor in maintaining required essential documents. Electronic TMF allows sponsor-cro visibility. Develop procedures for receipt and distribution clinical supply, and test and control articles; develop automated tool for demand/supply forecasting/tracking/reconciliation (i.e., interactive voice response system [IVRS]). Non-traditional monitoring resources; SOP and or monitoring plan describing traditional and non-traditional monitoring, precise instructions on how the monitor should undertake SDV. Direct method of verifying data in line listing corresponds to data in EDC; verify data identified in CRFs are consistent with source document by reviewing actual source data versus photocopies. Direct method of verifying critical source against protocol requirements. Adopt an automated CTMS for easy visibility of operations for continuous monitoring and auditing; ease of metrics.
Site Specific QC- Checklist Institutional Policies (i.e., CRA access to electronic medical records [EMR]) Qualifications and Training (i.e., ancillary) Source Documentation Collection Points Delegation of Authority/Responsibilities Adverse Events/Serious Adverse Events Con Meds History and Physicals Screening/Enrollment/Protocol Deviation Logs Laboratory Data Standard or Protocol Investigational Product (IP) Accountability
Elements Risk-Based Monitoring Checklist Identify regulatory or global standards Identify risks related to resources (i.e., key personnel back-up) and systems (i.e., clinical data management system) Identify key processes and plans related to ensuring quality data is collected, reviewed and reported Identify QA/QC activities around key processes
Regulatory and Global Standards 21 CFR Part 312.50 & 812.40 21 CFR Part 11 ICH GCP E6 5.18.3 FDA Draft Guidance on Risk-Based Monitoring ALCOA and Good Documentation Practices 16
Risks Related to Resources Back-up for key personnel (i.e., data manager, monitors etc.) Back-up for Site personnel (i.e., study coordinator, sub-investigators) Vendor (i.e., labs) support and oversight Electronic systems capabilities 17
Key Processes Protocol design and development Maintaining the audit trail Plans (i.e., monitoring, data management ) Data validation (i.e., ongoing data review plans) Centralized and on-site monitoring activities 18
QA/QC Activities Prequalification Site and Vendor Audits System Validation (i.e., EDC, CDMS) Process Validation (i.e., manual edit checks, line listing generation) Periodic data review (i.e., EDC, trip reports, Site QC source documentation) 19
Putting it all Together Define the risks and develop the controls to assure quality data
Summary Redefine monitoring from a nontraditional perspective Identifying risks is the first step in monitoring The checklist approach establishes steps in a complex iterative research process Effective monitoring is key to assuring quality research 21
Thank You! Jan Holladay Pierre, MPH Quality Principal Leader DynPort Vaccine Company LLC, A CSC Company bpierre2@csc.com www.csc.com/dynport