1. Process Risk Assessment Model Robert C. Menson, PhD

2. What Risks Must Be Managed? Risk to safety of patients, users, handlers Business Regulatory Product liability

3. Intended Use/Intended Purpose • Use of a Product, Process or Service in accordance with the specifications, instructions and information provided by the manufacturer ANSI/AAMI/ISO 14971:2000, definition 2.5

4. PAT(Process Analytical Technologies) • Systems for the analysis and control of manufacturing processes based on timely measurement during procession of critical quality parameter and performance attributes of raw and in-process materials and processes, to assure acceptable end-product quality at the completion of the process. FDA Subcommittee on PAT Proposed Definition

5. Assessment Elements of the Risk Management Process • Risk Analysis • Risk Evaluation • Risk Control • Post-Production Information Management

6. Risk Assessment Tools • Risk Matrix • PHA= Preliminary Hazard Analysis • FTA=Fault Tree Analysis • FME(C)A=Failure Mode Effects (Criticality) Analysis • HAZOP=Hazard Operability Analysis • HACCP=Hazard Analysis and Critical Control Point

7. FMEA Model

8. Material Activity Destination HAZOP Model Design Statement Transfer Powder Hopper

9. HAZOP

10. HACCPHazard Analysis and Critical Control Point • Risk Management System • Biological Hazards • Chemical Hazards • Physical Hazards • Requires • Prerequisite Quality System Program • Traditionally GMPs

11. Map Process 1. Risk Assessment 2. ECP Analysis 3. ECP Review Matrix 4. ECP Action Plan Risk Assessment Process

12. Create SOD Tables • Severity (S) • Link to end product functional failure • Medical Department involvement • Occurrence (O) • Use historical data • Similar processes products • Detection (D) • Method validation studies • Historical data

13. Evaluation Rules • Concept of ECP: • A process that is in control ( i.e. does not produce significant defects) but is very difficult to verify by testing. • The corollary is a process with a "high" level of defects that can be detected before shipment to the end user. • If (S) >5 and (D) or (P) >5 then an ECP is assigned.

14. Risk Assessment Decision Tree

15. Risk Assessment Decision Tree

16. Risk Assessment Decision Tree

17. Risk Assessment Decision Tree

18. Risk Assessment Document Step 1: Identify Risks Using Process Map • Convene participants from all relevant areas (Production, QA, QC, Packaging…) • Identify and rate failure modes for each process step by severity, probability, and detection • Assign Essential Control Points (ECP) based on ratings Robert C. Menson, PhD 18

19. Risk Assessment Document ECP Plan Document Step 2: Identify key elements of ECPs • Migrate ECPs from Risk Assessment to ECP Plan • Collect relevant Information (SOP#s, Equipment used, Training documents…) • Assign process drivers/ owners for each ECP in the Plan Robert C. Menson, PhD 19

20. ECP Plan Document Risk Review Matrix Step 3: Compile Risk Review Matrix • Break each ECP into review tasks based on SOP’s, trainings, and other documents • Each item # created is a distinct action item Robert C. Menson, PhD 20

21. Risk Review Matrix Step 4: Create Remedial Action Plan • Prioritize each item # and assign responsibilities and completion dates • Track items to completion Robert C. Menson, PhD 21