FDA recently endorsed the Risk Management approach described in ICH Q9. I presented this a year ago to ASQ Philadelphia. Still relevant today!

1. An Introduction to Risk Management Michael D. Kaufer, MBA, MS CGMP Solutions, Inc.

3. Learning Objective #1 ICH Q9

7. Figure 1.1: Stakeholders

9. Figure 1.2: Drug Product Lifecycle

11. Figure 1.3: Typical Risk Management Process

13. Learning Objective #2 What are the basics of Risk?

21. Learning Objective #3 Risk Tools

24. Figure 1.6: Cause-and-Effect Diagram for the elements of process validation

25. Figure 1.7: Brainstorming how do we clean equipment & facilities?

26. Figure 1.8: Decision Tree - do I look for another job or start-up my own firm?

27. Figure 1.9 Basic Flowchart Shapes

28. Table 1.1 Example of a Matrix (using risk rankings or weightings) Criteria Factors-to-be-considered Points No. of APIs Score I. Type of product being developed or transferred A. Non-sterile solutions 1 1 2 ≥ 3 B. Non-sterile suspensions 2 1 2 ≥ 3 C. Semi-solids 3 1 2 ≥ 3 D. Solid dosage (tablets) 4 1 2 ≥ 3 E. Solid dosage (capsules) 5 1 2 ≥ 3 F. Solid dosage (lozenges) 6 1 2 ≥ 3 G. Drug coated patches 7 1 2 ≥ 3 H. Terminally sterilized products 8 1 2 ≥ 3 I. Injectable drug (aseptically produced) 9 1 2 ≥ 3 J. Injectable drug (aseptically produced and lyophilized) 10 1 2 ≥ 3 K. Implantable device with drug component(s) 11 1 2 ≥ 3 Criteria Factors-to-be-considered Points Weight Score II. Non-API-related changes to components & composition A. Changes are those that are unlikely to have any detectable impact on formulation quality and performance. 1 Multiply by score from Section I B. Changes are those that could have a significant impact on formulation quality and performance. 2 C. Changes are those that are likely to have a significant impact on formulation quality and performance. 3

30. Table No. 1.2: Failure Severity Rating Serious adverse event 10 Extreme effect Adverse event 8 Major effect Customer declines further use 6 Significant effect Customer complains 4 Moderate effect Customer is dissatisfied; still uses product 2 Slight effect Failure would have no effect on the customer 1 No effect Criteria Severity Rating Effect

31. Table No. 1.4: Failure Occurrence Rating Very high number of process deviations 1 in 5 8 Very high High number of process deviations 1 in 10 7 High Frequent process deviations 1 in 20 6 Moderately high Moderate number of process deviations 1 in 80 5 Medium Occasional process deviation 1 in 400 4 Low Few process deviations 1 in 2,000 3 Slight Very few process deviations 1 in 4,000 2 Very slight Process deviation very unlikely 1 in 10,000 1 Remote Criteria Failure Rate Rating Occurrence

32. No controls in place 10 Impossible Controls not aligned to critical quality attributes 9 Remote Controls are experimental 8 Very slight Controls being concurrently validated 7 Slight Low likelihood of detection; low usage of inspection and testing; inspections & tests are not optimal 6 Low Medium likelihood of detection; heavy use of inspection between process steps 5 Medium Moderate likelihood of detection; heavy use of inspection during process steps 4 Moderately high Detection is very likely; validated lab methods 3 High Detection is likely; heavy use of inspection between & during process steps (with some automation) 2 Very high Detection is certain; validated on-line PAT controls 1 Almost certain Criteria for Controls in Place Rating Detection Ability Table No. 1.5: Detection Rating (for failure modes)

33. Learning Objective #4 Principles of Risk Management

40. Thank you! Questions?