Applying Risk Management Principles to Drive …

1 Applying Risk Management Principles to Drive quality Management system effectiveness Carlos Monteagudo Director of quality Assurance Amgen, Inc. PQRI 2nd FDA/PQRI Conference on Advancing Product quality October 6th, 2015. Presentation Agenda Drivers and Basic Principles for Integrating Risk Management into quality Management Systems Examples of Risk Management Integration into quality Management Systems To Drive Efficiency and effectiveness Development quality Defect Investigations Change Control Management Product Complaints Equipment Commissioning and Qualification Supplier Auditing Driving Periodic Continuous Improvement Periodic Reviews and Risk Management 2. Risk Management Enables effectiveness of quality Management Systems quality risk Management is integral to an effective pharmaceutical quality system . It can provide a proactive approach to identifying, scientifically evaluating, and controlling potential risks to quality .

2 ICH-Q10. Risk Management Will: Drive the right focus in the quality Management system to Ensure Patient Safety and Important quality Attributes Help define the level of effort driven by the quality system Support risk-based decisions in the quality system Integration of Risk Management Principles into Key Areas of quality Systems Enables effectiveness Development Evaluation of Change quality Control quality Defects Management system Periodic Auditing and Product Inspection Reviews ICH Q10 and SG3/N15R8 Document from GHTF Study Group 3 Provides Guidance on Integration of quality Risk Management into quality Management system Use Risk Assessments to Prioritize and Focus Development Effort to Ensure Patient Safety Understanding of the relationship between Maintains the focus on Critical quality Attributes minimizing risk to patients and quality Target (Safety and Efficacy). Benefits of quality Risk Management in Product Development Directs resources to focus Development of robust on key development areas control strategy to support that have high impact on decision making process product quality ensuring product quality Risk Assessments Guide and Prioritize Product Development Efforts Product Process Knowledge Control Strategy Knowledge Target Product Life Cycle Profile Management Critical quality Design Attributes Space Process Process Process Final Control Platform Performance Development Characterization Strategy Knowledge Draft Control Verification Clinical Studies Strategy Safety and Efficacy data Risk Risk Risk Risk Assessment Assessment Assessment Assessment Adapted from CMC Biotech Working Group A-mab case study Risk Analysis are Key Components of Device and Combination Product Design Controls User Risk Needs Analysis Design Inputs

3 Verification Validation Design Design Output Combo Product Design Review Risk Management Can Help Define Requirements of quality Defects Investigations Establish criteria in the investigation Management system to allow you to focus on events with potential impact to product quality or safety Use risk analysis in the Investigation process as a tool to assess potential causes of an event or patient safety risk Maintain applicable risk assessments with new information Consider Incidental and Periodic Risk Risk Principles Can Be Used to Define the Level of Effort in quality Investigations Example of a Risk-Based Classification Scheme For Investigations Low Risk Event Medium Risk Event High Risk Event No or Unlikely Risk Moderate Risk Significant Risk Requirements: Requirements: Requirements: 1. Document the event 1. Document the event 1. Document the event 2. Document correction or 2.

4 Execute Root Cause 2. Execute Root Cause Analysis justification for no further Analysis 3. Testing Assess Extent of Impact action 3. Testing for Potential Impact to Product quality & Safety to Product quality & Safety 4. Execute Patient Safety 4. Assess Impacted Lots Assessment 5. Notify quality Disposition 5. Asses Impacted Lots individual & Qualified Person 6. Notify quality Disposition 6. Corrective Actions Taken individual, Qualified Person and 7. Risks of Continued Senior Management Processing 7. Corrective Actions Taken 8. Risks of Continued Processing QA Approval Level: QA Approval by: QA Approval by: quality Staff Level 6 quality Management or Higher quality Staff Level 5. Investigation Efforts Are Commensurate to the Risk To Patient Safety 9. Efforts Taken in a Change Control Can Be Defined By A Risk Based Approach Change Risk Level Requirements Low Document change execution in Change Control.

5 No impact assessments needed. Medium Impact Assessment by Applicable Areas. Use of Risk Management Process to assess risk Report Change to Agency if Required Maintain Tracking of Release Product High Impact Assessment by Applicable Areas. Use of Risk Management Process to assess risk Obtain Agency Approvals, if required. Do not Distribute Product Until Closure of Change Control Use Risk Management Data to Configure Complaints Management system Align definition of complaint codes with Identified Hazards and Failures Establish connectivity to risk Management information to assess complaints with unknown causes Align complaints trending threshold with risk rating criteria to facilitate initiation of risk reviews in pre- determine frequencies Risk Likelihood Estimated Likelihood Threshold to Trigger Rating Probability Risk Review Remote - between and 10 complaints / 1M units 5..0001% distributed Apply Risk Management Concepts to Focus Validation Efforts To Ensure quality ASTM E2500 Provides a process Framework Use a science and risk-based approach to assure that GMP.

6 Equipment Fit for use Perform satisfactorily Ensures Product quality Example of A Risk Based Model For Equipment Commissioning and Qualification Risk Assessment Will Ensure Controls Are Established For Equipment Related Elements Impacting Critical quality Attributes Example of a Risk Based Audit Scheme for Raw Material Suppliers Supplier Preference Assessment Supplier Criticality Risk QMS Action High High Audit Frequency, CAPA Plan, Full spec Incoming testing. Medium Low Audit Frequency, CI Plan, Reduced Incoming testing Low Low Frequency, Incoming verification of Certificate of analysis Integration of Risk Management Into Periodic Reviews Drive Continues Improvement Production Market Industry and Agency Nonconformities Complaints New requirements Process Changes Adverse Events Information on similar Supplier Changes Customer Inquiries products in the market NO. Known Hazard or Product Risk Failure?

7 Acceptable? YES NO. Risk File Update YES. YES Corrective/Preve Likelihood of ntive Action Risk Change? NO. Continue Monitoring Data Trending Gain Efficiency and quality Management system effectiveness by Integrating Risk Management Principles Integrating Risk Management into the quality Management system can Drive effectiveness and focus efforts on ensuring patient safety It's not about doing risk assessments, It's about using risk Principles to Drive effectiveness . Ensure compliance, integration of risk Principles cannot justify not complying with requirements.