辉瑞制药公司fmea培训课程教材(英文)(36页)-质量工具(编辑修改稿)

辉瑞制药公司fmea培训课程教材(英文)(36页)-质量工具(编辑修改稿)内容摘要：

ement process Example of a CMC Regulatory Decision: Acceptability of a Post Approval Manufacturing Process Change  Original NDA or ANDA = CMC Quality amp。 Performance (―Insurance‖) Contract  For example in ANDA’s Regulatory mitments = Conditions in executed batch records  Prior Approval Supplement* (PAS)  Product conforms with all established specifications  But ―Specifications do not tell the whole story‖  ., Shelflife and/or bioavailability may have changed and/or a new impurity may be introduced that may not be detected with established analytical methods,…sponsor may not adequately qualify changes (inspection frequency may not be sufficient),…. *prior approval supplement for process optimization and continuous improvement efforts Company X ―Goes Lean‖  “ Cycletime reduction subgroup members, for example, examine each process function, for example, dispensing, roller paction and pression, to determine how to speed up changeover and get equipment to run faster and more efficiently.‖  ―The team solicits ideas at regular meetings and via . The ideas are then rated from 1 to 10 based on bang for the buck to reduce cycle time, and on how difficult they would be to ., whether they will require validation or prior FDA approval.‖ Post Approval Process Change (SUPAC Guidance) ―Within‖ (Change Target setting) ―Outside‖ Current Uncertainty Management  At the operational level the most efficient approach for managing uncertainty is ―demand management‖  Strict ―checking the box‖ process using prespecified requirements (remendations) and procrustean standards  FDA guidance documents, 483 observations,..  90% CI 80125%, inprocess blend uniformity tests, ….. SOP’s,….. Current Demand Management: Characteristics  For conventional products and manufacturing processes easy to implement, supervise, and mange  Decision responsibility is deferred to a set of ―procrustean‖ standards liability distributed to the entire pharmaceutical munity (., via USP, AAPS, etc.)  For innovative and/or plex products and processes no one is willing to take responsibility for decisions (., develop guidance document) – decision liability is then on the person willing to take a decision. Current Demand Management: Characteristics  Innovation and continuous improvement slows down and inefficiency increases  The level of quality assurance achieved is difficult to measure and is buried in historical mindset and clinical variability  With increasing plexity a major failure is necessary to signal inadequacies of the system – such a failure is often the only approach to introduce new regulations or improved decision criteria  Challenge to and alternate approaches to current procrustean standards difficult to prove and debates drain resources Without Continuous (Community) Learning: Demand Management is “static” until a crisis is created, it then reacts to replace a current procrustean standard with another. Continuous Improvement: Enhancing Customer Satisfaction Reducing Variability “ Special Cause‖ or ―Common Cause‖ Stable Yes。 Capable? Unstable Corrective Actio。