Process Risk Assessment Model

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