2. 1 Process Risk Assessment Model Robert C. Menson, PhD

3. 2 What Risks Must Be Managed? Business Product liability Regulatory Risk to safety of patients, users, handlers

4. Robert C. Menson, PhD 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

5. Robert C. Menson, PhD 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

6. Robert C. Menson, PhD 5 Elements of the Risk Management Process Risk Analysis Risk Evaluation Risk Control Post-Production Information Assessm ent Management

7. Robert C. Menson, PhD 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

8. Robert C. Menson, PhD 7 FMEA Model

9. Robert C. Menson, PhD 8 HAZOP Model Design Statement Activity Material Destination TransferPowderHopper

10. Robert C. Menson, PhD 9 HAZOP TransferMaterialDestination NoValve closed Line blocked Pump broken Tank emptyValve closed Hopper full MorePump fastLarger tank Inaccurate gage Other than Liquid Wrong powder

11. Robert C. Menson, PhD 10 HACCP Hazard Analysis and Critical Control Point Risk Management System Biological Hazards Chemical Hazards Physical Hazards Requires Prerequisite Quality System Program Traditionally GMPs

12. Robert C. Menson, PhD 11 Risk Assessment Process Map Process 1. Risk Assessment 2. ECP Analysis 3. ECP Review Matrix 4. ECP Action Plan

13. Robert C. Menson, PhD 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

14. Robert C. Menson, PhD 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.

15. Robert C. Menson, PhD 14 Risk Assessment Decision Tree

16. Robert C. Menson, PhD 15 Risk Assessment Decision Tree

17. Robert C. Menson, PhD 16 Risk Assessment Decision Tree

18. Robert C. Menson, PhD 17 Risk Assessment Decision Tree

19. 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 Risk Assessment Document Robert C. Menson, PhD18

20. Step 2: Identify key elements of ECPs Migrate ECPs from Risk Assessment to ECP Plan Assign process drivers/ owners for each ECP in the Plan Collect relevant Information (SOP#s, Equipment used, Training documents…) Risk Assessment Document ECP Plan Document Robert C. Menson, PhD19

21. 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 ECP Plan Document Risk Review Matrix Robert C. Menson, PhD20

22. Step 4: Create Remedial Action Plan Prioritize each item # and assign responsibilities and completion dates Track items to completion Risk Review Matrix Robert C. Menson, PhD21