Use of Risk Management in Pharmaceutical Manufacturing

1. Use of Risk Management in Pharmaceutical Manufacturing Manufacturing Subcommittee Meeting September 17, 2003

2. Risk Management Process consisting of well-defined steps which, when taken in sequence, support better Decision Making by contributing to a greater insight into risks and their impacts

3. More High ManufacturingScience III Risk II I Less Low Regulatory Process Category III- High; II-Medium; I-Low Quality By Design Model

4. Developing Relationship between Manufacturing Science and Risk • Manufacturing Science α Risk • Solve for α? • How can it be solved consistently and systematically using validated models?

5. Manufacturing Science • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure

6. Manufacturing Science • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure • FMEA uses a systematic way of examining all ways in which a failure can occur within a process, and then identifies all the potential root causes of each failure. For each failure an estimate is made on the effect of the whole system, in our case, Quality. This would include how often the failure could occur, the severity of the failure, and the ability to detect. This is the start of defining the critical quality attributes and parameters.

7. Manufacturing Science • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure • Using FMEA to define the critical quality attributes and parameters, define the process capability to meet the acceptable ranges. If process capability is well within acceptable range, then additional risk mitigation is not necessary. If process capability cannot ensure process reliability within acceptable ranges, then risk mitigation strategies should be explored.

8. Manufacturing Science • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure • A risk mitigation strategy considered when critical quality attributes and parameters cannot reliably be ensured in the process to meet acceptable ranges.

9. Manufacturing Science • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure • A risk determination can be made by the FDA based on the outcome of comprehensive Quality System inspectional outcomes for specific sites.

10. Developing Relationship between Manufacturing Science and Risk • Primary Attributes • Process Knowledge • Process Capability • Manufacturing Technology • Process Control Technology • Quality Systems Infrastructure • Risk will equal the aggregate evaluation of the elements above as determined by the manufacturer.