際際滷

際際滷Share a Scribd company logo

FDA News Presentation

Download as PPT, PDF
B
Boris Videlov

The document discusses integrating pharmacovigilance quality management systems (QMS) to ensure compliance and quality across various pharmacovigilance processes. It outlines key considerations for establishing a QMS including regulations, metrics, customizing electronic systems, and managing quality for clinical trial data, contracting, inspections/audits, and expedited individual case safety reports. The QMS aims to prospectively and retrospectively monitor quality across pharmacovigilance activities.

1 of 26
Downloaded 32 times
Integrating Pharmacovigilance Into Quality Management System First Annual CAPA Congress Boris Videlov
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
Why have a Pharmacovigilance QMS? Regulations Governmental: US CFR, EU (EMEA, MHRA, etc) International: ICH (Q 9 &10), CIOMS, ISO Professional/Certification: BARQA, TQM, 6 , ASQ, Lean Industry Standards Good Pharmacovigilance Practice (GPvP) http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodPharmacovigilancePractice/index.htm GCP and Good Documentation Practices Company Procedures Corporate Requirements Process requirement from Corporate Quality Pharmacovigilance Departmental requirement Contractual Agreements Regulatory Inspections
Pharmacovigilance Process
Monitoring Metrics Reports Focused, Intelligent, Simple Ensure system upgrades do not affect the reports Use of various Report Systems: SDB, BO, QMS Establish Reports Tracking, Periodicity, Targets, and Ranges Define Trend Discuss with the appropriate audience and close the loop
Metrics Examples
Considerations for QMS Paper vs. Electronic vs. Hybrid If Electronic Validated (DB) vs. not-validated (xls) Commercial system vs. in-house developed system Internal Knowledge vs. External Consulting Inspection commitment vs. company initiative Availability of financial resources and people Regulatory Risk Assessment Benefits vs. Cost Analysis
Electronic System(s) Selection Single system versus multiple systems Available Systems Off-the-shelf system use Re-configuration: effort and cost New System Selection System/Vendor selection New System Implementation/validation: effort and cost
Potential Challenges Unnecessary standard fields Integration with other systems Drug Safety Database Reporting Tools Learning (Knowledge) Management System SOP/Document Management Record structure Sub-records (hierarchy) Linking related records Support for table format data Develop customized intelligent reports Support Continuous Improvement
Likely Customization and Enhancements Custom Fields Custom Tables/Grids Custom Reports and integration with third-party Report Builders Data Export in desired format Links to other databases Activities completion timeframe flexibility On-screen Help Tips and other Links to Procedures or User Guides
Identification of Quality & Compliance Issues Data coming from different sources and systems Use of dashboards to monitor data simultaneously
Quality Management of Document Review Shared company/departmental responsibility Routine and Ad-hoc Document Types: Internal Procedural Documents External Procedural Documents Clinical Trial Protocols/Amendments CRO documents Safety Data Exchange Agreements Marketing Materials System Integration with Document Management System
Quality Management of Contracting Company-wide process Contractors viewed by the authorities as extensions of the company Difficult to control affiliates contractual activities Joint effort between Drug Safety, Product Development, Procurement, Clinical Development, Corporate Quality, Marketing, Legal, and other departments Negotiate inter-departmental process Use of Contract Management System Requires subsequent Training and Monitoring
Quality Management of In- and Out-licensing First step - Due Diligence Licensing Agreements/Development Agreements/Quality Agreements Safety Data (PhV) Exchange Agreements Process for development and maintenance Consider using a database (eg, Contract Management System) Maintain key timeframes reference document/report Include compliance clauses: Compliance with applicable regulations and agreements Response timeframes for compliance issues PhV Audits Escalation of issues Penalties
Quality and Compliance of CT Data (slide 1 of 2) Paper SAE Form vs. EDC Before the trial begins CT Protocol review SAE and unblinding sections Forms customization Site/Principal Investigator Selection Coordinator and Investigator Meetings Investigator Binder/CD preparation Training materials
Quality and Compliance of CT Data (slide 2 of 2) After the trial begins Compliance Monitoring Timeframes for SAE Form submission to Sponsor (incoming) Query response timeframes (incoming) Investigator notifications (outgoing) Quality SAE Form completeness and accuracy Query volume to sites and trends Discrepancies between Clinical Database and Drug Safety Database during reconciliation CRO Audits CAPA collaboration with Corporate Quality & Clinical Development/Operations
Compliance and Quality Monitoring of Business Partners Compliance Monitoring Exchange Metrics Reports for compliance with timelines Identify non-conformances Request Reason for Delay and CAPA Trend and perform Effectiveness Checks Quality Monitoring and feedback from Drug Safety Operations Actions Official Notification/Memorandum Minuted teleconference to discuss CAPA F2F meeting PhV Audit Escalation to Corporate/Legal
Compliance with Company AE Reporting Policy Governance Corporate Standard for AE Reporting by company employees Documented Training Data from multiple databases: HR System or Training Management System to monitor overall training and retraining compliance Drug Safety Database for monitoring compliance with the policy QMS for tracking of compliance, trends, RCA, and CAPA Enforcement is a joint effort
Compliance Management of Expedited ICSRs Useful QMS fields ( 1 ) The data is usually available in SDB ( 2 ) Additional compliance data is required Clock Start Date 1 /Due Date 1 /Actual Submission Date 1 /Delay in Days 2 Additional information 2 Group Responsible Company Name 1, 2 External vs. Internal group 2 Department/Functional Group 1, 2 Reason for Delay 2 Delay in Days 2 Workflow Step where the delay occurred 1, 2 ID fields ICSR ID 1 Reporter (Business Partner) ID 1 Version # 1 Approval # 1 Product Name(s) 1 Authority fields Health Authority 1 Report Type 1
Compliance and Quality Management of Aggregate Reports Interdepartmental Process Use of Document Management System Report Schedule Tracking In-Process Quality Checks and Sign-offs Submission Tracking and Monitoring Subject to Retrospective Quality Review
Quality Management of ICSRs Prospective Quality Checks Performed in Drug Safety Database, some may be documented in QMS Electronic (system) Peer/Supervisor/Medical Review Retrospective Quality Review Performed in DSB, documented in QMS All vs. Targeted data fields Prioritization of ICSRs to be reviewed By expeditedness By case type By case volume By known issues By available resources
Retrospective Quality Review A defect will never occur until the unit has passed final inspection! Murphys Law Periodic retrospective quality review on a sample of items (ICSRs, aggregate reports) Use standard statistical formula/calculations [example] SS = Z 2 * (p) * (1-p) / c 2 Determine appropriate Sample Size, based on statistical parameters: Confidence Interval Confidence level Percentage picking a choice Additional criteria to select priority items (eg, expedited reports) Trending, RCA, CAPA, and Effectiveness Check
Quality Management of the Signaling Process RCA: Potential Safety Signal Identification Safety Signal Investigation Safety Signal Evaluation Impact Analysis CAPA: Changes to Reference Safety Information Aggregate Reports Pre-planned Actions in REMS/RMP/Risk Maps Other Actions
Quality Management of Inspections/Audits Records Classify Inspections/Audits External Regulatory Inspections Business Partner Audits Internal Internal Audits Business Partner/CRO Audits Tracking of specific data Request Type/Details Data Date Range Date Requested/Date Provided/Taken off-site Findings/Observations Root Cause Analysis and Company Commitments (CAPA)
Quality Management of Data Verification Ensures the integrity and quality of the entire database or data subset Full data verification vs. sample Routine Clinical Database Product Quality Complaints Database Medical Communications Database Ad hoc Database Upgrade/Migration Data(base) Transfer Data Cleansing
Thank you for your attention! www.LinkedIn.com

More Related Content

FDA News Presentation

  • 1. Integrating Pharmacovigilance Into Quality Management System First Annual CAPA Congress Boris Videlov
  • 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. Why have a Pharmacovigilance QMS? Regulations Governmental: US CFR, EU (EMEA, MHRA, etc) International: ICH (Q 9 &10), CIOMS, ISO Professional/Certification: BARQA, TQM, 6 , ASQ, Lean Industry Standards Good Pharmacovigilance Practice (GPvP) http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodPharmacovigilancePractice/index.htm GCP and Good Documentation Practices Company Procedures Corporate Requirements Process requirement from Corporate Quality Pharmacovigilance Departmental requirement Contractual Agreements Regulatory Inspections
  • 5. Monitoring Metrics Reports Focused, Intelligent, Simple Ensure system upgrades do not affect the reports Use of various Report Systems: SDB, BO, QMS Establish Reports Tracking, Periodicity, Targets, and Ranges Define Trend Discuss with the appropriate audience and close the loop
  • 7. Considerations for QMS Paper vs. Electronic vs. Hybrid If Electronic Validated (DB) vs. not-validated (xls) Commercial system vs. in-house developed system Internal Knowledge vs. External Consulting Inspection commitment vs. company initiative Availability of financial resources and people Regulatory Risk Assessment Benefits vs. Cost Analysis
  • 8. Electronic System(s) Selection Single system versus multiple systems Available Systems Off-the-shelf system use Re-configuration: effort and cost New System Selection System/Vendor selection New System Implementation/validation: effort and cost
  • 9. Potential Challenges Unnecessary standard fields Integration with other systems Drug Safety Database Reporting Tools Learning (Knowledge) Management System SOP/Document Management Record structure Sub-records (hierarchy) Linking related records Support for table format data Develop customized intelligent reports Support Continuous Improvement
  • 10. Likely Customization and Enhancements Custom Fields Custom Tables/Grids Custom Reports and integration with third-party Report Builders Data Export in desired format Links to other databases Activities completion timeframe flexibility On-screen Help Tips and other Links to Procedures or User Guides
  • 11. Identification of Quality & Compliance Issues Data coming from different sources and systems Use of dashboards to monitor data simultaneously
  • 12. Quality Management of Document Review Shared company/departmental responsibility Routine and Ad-hoc Document Types: Internal Procedural Documents External Procedural Documents Clinical Trial Protocols/Amendments CRO documents Safety Data Exchange Agreements Marketing Materials System Integration with Document Management System
  • 13. Quality Management of Contracting Company-wide process Contractors viewed by the authorities as extensions of the company Difficult to control affiliates contractual activities Joint effort between Drug Safety, Product Development, Procurement, Clinical Development, Corporate Quality, Marketing, Legal, and other departments Negotiate inter-departmental process Use of Contract Management System Requires subsequent Training and Monitoring
  • 14. Quality Management of In- and Out-licensing First step - Due Diligence Licensing Agreements/Development Agreements/Quality Agreements Safety Data (PhV) Exchange Agreements Process for development and maintenance Consider using a database (eg, Contract Management System) Maintain key timeframes reference document/report Include compliance clauses: Compliance with applicable regulations and agreements Response timeframes for compliance issues PhV Audits Escalation of issues Penalties
  • 15. Quality and Compliance of CT Data (slide 1 of 2) Paper SAE Form vs. EDC Before the trial begins CT Protocol review SAE and unblinding sections Forms customization Site/Principal Investigator Selection Coordinator and Investigator Meetings Investigator Binder/CD preparation Training materials
  • 16. Quality and Compliance of CT Data (slide 2 of 2) After the trial begins Compliance Monitoring Timeframes for SAE Form submission to Sponsor (incoming) Query response timeframes (incoming) Investigator notifications (outgoing) Quality SAE Form completeness and accuracy Query volume to sites and trends Discrepancies between Clinical Database and Drug Safety Database during reconciliation CRO Audits CAPA collaboration with Corporate Quality & Clinical Development/Operations
  • 17. Compliance and Quality Monitoring of Business Partners Compliance Monitoring Exchange Metrics Reports for compliance with timelines Identify non-conformances Request Reason for Delay and CAPA Trend and perform Effectiveness Checks Quality Monitoring and feedback from Drug Safety Operations Actions Official Notification/Memorandum Minuted teleconference to discuss CAPA F2F meeting PhV Audit Escalation to Corporate/Legal
  • 18. Compliance with Company AE Reporting Policy Governance Corporate Standard for AE Reporting by company employees Documented Training Data from multiple databases: HR System or Training Management System to monitor overall training and retraining compliance Drug Safety Database for monitoring compliance with the policy QMS for tracking of compliance, trends, RCA, and CAPA Enforcement is a joint effort
  • 19. Compliance Management of Expedited ICSRs Useful QMS fields ( 1 ) The data is usually available in SDB ( 2 ) Additional compliance data is required Clock Start Date 1 /Due Date 1 /Actual Submission Date 1 /Delay in Days 2 Additional information 2 Group Responsible Company Name 1, 2 External vs. Internal group 2 Department/Functional Group 1, 2 Reason for Delay 2 Delay in Days 2 Workflow Step where the delay occurred 1, 2 ID fields ICSR ID 1 Reporter (Business Partner) ID 1 Version # 1 Approval # 1 Product Name(s) 1 Authority fields Health Authority 1 Report Type 1
  • 20. Compliance and Quality Management of Aggregate Reports Interdepartmental Process Use of Document Management System Report Schedule Tracking In-Process Quality Checks and Sign-offs Submission Tracking and Monitoring Subject to Retrospective Quality Review
  • 21. Quality Management of ICSRs Prospective Quality Checks Performed in Drug Safety Database, some may be documented in QMS Electronic (system) Peer/Supervisor/Medical Review Retrospective Quality Review Performed in DSB, documented in QMS All vs. Targeted data fields Prioritization of ICSRs to be reviewed By expeditedness By case type By case volume By known issues By available resources
  • 22. Retrospective Quality Review A defect will never occur until the unit has passed final inspection! Murphys Law Periodic retrospective quality review on a sample of items (ICSRs, aggregate reports) Use standard statistical formula/calculations [example] SS = Z 2 * (p) * (1-p) / c 2 Determine appropriate Sample Size, based on statistical parameters: Confidence Interval Confidence level Percentage picking a choice Additional criteria to select priority items (eg, expedited reports) Trending, RCA, CAPA, and Effectiveness Check
  • 23. Quality Management of the Signaling Process RCA: Potential Safety Signal Identification Safety Signal Investigation Safety Signal Evaluation Impact Analysis CAPA: Changes to Reference Safety Information Aggregate Reports Pre-planned Actions in REMS/RMP/Risk Maps Other Actions
  • 24. Quality Management of Inspections/Audits Records Classify Inspections/Audits External Regulatory Inspections Business Partner Audits Internal Internal Audits Business Partner/CRO Audits Tracking of specific data Request Type/Details Data Date Range Date Requested/Date Provided/Taken off-site Findings/Observations Root Cause Analysis and Company Commitments (CAPA)
  • 25. Quality Management of Data Verification Ensures the integrity and quality of the entire database or data subset Full data verification vs. sample Routine Clinical Database Product Quality Complaints Database Medical Communications Database Ad hoc Database Upgrade/Migration Data(base) Transfer Data Cleansing
  • 26. Thank you for your attention! www.LinkedIn.com

Editor's Notes

  • #2: Good Morning My name is Boris Videlov, and I am responsible for all quality and compliance-related activities in the Global Drug Safety Department of Forest Research Institute. I will share with you today my views on what constitutes a QMS for Pharmacovigilance and some practical considerations on how to get there. Will provide information on SOME of the key elements of a Pharmacovigillance Quality management System and how to build it.
  • #4: FDA: CFR 21 Part 820, 211 Quality System Inspection Technique (QSIT) BARQA - British Association of Research Quality Assurance ASQ - American Society for Quality ISO 9001:2000
  • #6: Our metrics are our canaries in the coal mine. However, we need to be able to read our metrics. In the example here, there is a huge difference if the canarys legs are pointing up - the course of action would be keep digging or Run!.
  • #7: When I was working on the presentation I was thinking how to depict our process, and this is what I came up with. Apologize to the vegetarians, it can be used as a vegie-grinder.
  • #15: Not to be tracked in QMS Subject to regulatory Audits Be mindful of the Regulatory Clock Start Date Compliance with applicable regulations Timeframes to respond to compliance issues some difficulties Audit Clause - some difficulties Escalation/Penalties - some difficulties from Corporate/Legal Consider using a Contract Management tool Maintain key timeframes reference document/report
  • #16: # of queries Completion of SAE form Discrepancies between the CRF and SAE form
  • #17: # of queries SAE Form completeness and accuracy Quality review of samle Discrepancies between the CRF and SAE form
  • #24: Signal confirmation Preplanned CAPA, such as labeling changes, black box warning, up to withdrawal from the market.
  • #25: Inspections & Audits are a important and highly visible source of quality records and most often company-wide CAPA. We always speak about Inspection readiness, but are we always ready? Anything said in Latin sounds profound