Manufacturing Science (PDF) - PQRI

Manufacturing Science(and and the associated regulatory processes)PQRI / FDA Workshop4/22/03Gerry MigliaccioPfizer Inc

Objective• Provide seeds for tomorrow’s workshopon the desired relationship betweenmanufacturing science and relatedregulatory processes.– Desired state should accommodate the needsall segments of industry and FDA.– Desired state should allow flexibility.– Desired state should encourage and facilitateinnovation but not penalize status quo.

Manufacturing ScienceDefinition• Consists of Five Elements– Product / Process Knowledge– Process Capability Data– Manufacturing Technology– Process Control Technology– Quality Systems Infrastructure

Product / Process Knowledge (K)• Development pharmaceutics• Critical to quality attributes offormulation• Critical to quality process parameters• Critical to quality product attributes• Impact of changes to critical to qualityparameters and attributes

Process Capability (CP K )• Data analysis of critical to qualityparameters and attributes.• Assessment of actual performance versusoriginal specifications.• Continuous trending.

Manufacturing Technology (T)• Equipment design and principles ofoperation• Facility design• Level of manual intervention versusautomation• Cleanability, , potential for cross-contamination

Process Control Technology (PC)• Instrumentation and sensors• Monitoring and reactive control versuscontinuous feedback loops• Remote versus at-line or on-line• Conventional versus process analyticaltechnologies• Traditional validation versus continuousquality verification

Quality Systems (QS)• cGMP Infrastructure at ManufacturingSite• Regulatory Inspection Performance• Recall Record

The FormulaeRisk ƒ (K, CP k , T, PC, QS)∴↑ Manufacturing Science ≡ ↓ RiskandRegulatory Process ∝ Risk

Manufacturing Science andRisk• Product / process knowledge will provideus with an initial assessment of the risk ofa quality issue.– What is the impact of deviations in level offormulation components on fitness-forfor-use?– What is the impact of deviations in critical-to-quality parameters on fitness-forfor-use?

Manufacturing Science andRisk• Process capability analysis will provideus with an assessment of:– Process variability and need for furtherprocess optimization– Ability to meet quality attributes required toassure safety and efficacy 100% of the time.

Manufacturing Science andRisk• Product /process knowledge coupled withprocess capability analysis allow us tocategorize the risk associated with agiven process.• Since knowledge is continuously obtainedand capability continuously analyzed, therisk classification can change over time.

Manufacturing Science andRisk• Manufacturing and Process ControlTechnology can be used to mitigate therisk associated with a process.– Process capability / robustness issues can beaddressed through the use of innovativemanufacturing technologies and processcontrols.

Regulatory Processes and Risk• Regulatory processes should beproportional to the level of risk.– Routine cGMP inspection frequency– Need for PAI’s– NDA content and approval process– Supplement content and approvalrequirements– Comparability protocols

The FormulaeRisk ƒ (K, CP k , T, PC, QS)∴↑ Manufacturing Science ≡ ↓ RiskandRegulatory Process ∝ RiskGreat concept, but how to we get there?

Key Units of Work• Define the data set required for FDA andIndustry to appropriately categorize risk.– Critical to quality attributes and parameters– CP K data• Development of an agreement betweenFDA and Industry on the use oftechnology to mitigate risk.

Key Success Factors• Firms must be willing to shareappropriate data with FDA.• FDA must demonstrate to firms whoinvest in technology that the regulatoryprocesses will allow for greater flexibility.• Firms who decide to proceed withcurrent approach should not bepenalized.