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Debugging Finished Goods Manufacture For A Popularly Prescribed Pharmaceutical

Debugging Finished Goods Manufacture For A Popularly Prescribed Pharmaceutical. Jean-Marie Geoffroy, Xavier Castells Abbott Laboratories Robert H. McCafferty, Curvaceous Software Limited. Background. Reasonably Large Database 106 Variables in Total 212 Lots Spanning Full Year’s Manufacture

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Debugging Finished Goods Manufacture For A Popularly Prescribed Pharmaceutical

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  1. Debugging Finished Goods Manufacture For A Popularly Prescribed Pharmaceutical Jean-Marie Geoffroy, Xavier Castells Abbott Laboratories Robert H. McCafferty, Curvaceous Software Limited

  2. Background • Reasonably Large Database • 106 Variables in Total • 212 Lots Spanning Full Year’s Manufacture • Raw Material, Logistical Information Also Tracked • History Of Issues • Granulation, Blending, Compression, And Coating Unit Processes Involved • Yield Loss And Associated Mechanisms Negligible • Variability Driving: • Test Cost • Idle Equipment Time • Dissolution Profile Anxiety

  3. Entire Spreadsheet in One Picture • Each Black Line An Observation • Missing Data Clustered At Bottom Of Axes

  4. Querying Against Variability And Yield • First Pass Approach Given Product Within Specifications • Considers All Standard Deviations Available In Dataset

  5. Variability Analysis (cont.) • Clear Temporal Patterns By Month, Possibly Day As Well

  6. Variability Analysis (cont.) • Adverse Results With Extended Hold Time • Different Gradients For Gran/Blend, Blend/Compress, Compress/Coat Delay • Also True Of Accumulated Time… Possible Hole In Blend/Compress Delay

  7. Cost Argument Analysis • Effectively Confirms All Items Discovered By Variability Analysis • No Relationship Between Yield And Tablets Tested (Different Mechanisms)

  8. Cost Analysis (cont.) • Adverse Signature In Raw Material 1 Characteristics • Map Directly To High Tablet Testing And Variability, Recent And Previous

  9. Dissolution Profile Analysis • Hardness Range Increases As Min Or Max Diverge From Spec. • Operators Taking Corrective Action (Too Hard/Soft) Only When Warranted • Standing Procedures Working

  10. Dissolution Profile Analysis (cont.) • Weight Range Increases As Min Or Max Diverge From Spec. • Operators Taking Corrective Action (Too Light/Heavy) Only When Warranted • Standing Procedures Working

  11. Dissolution Profile Analysis (cont.) • Clear Coating Process Sweet Spots • Nozzle To Bed Distance As Well As Pan Loading

  12. Analysis Results • Holistic View Taken… All Variables Considered Simultaneously • Clear Shift In Raw Material Constitution Driving High Variability • Problem Clearly Amplified By Unanticipated Hold Time Influence • Expected Temporal Patterns (Month and Campaign) Present, Mid- Month Hole In Daily Behavior Under Review • Manufacturing Procedures Confirmed Operating As Expected • High/Low Hardness Reaction • High/Low Weight Reaction

  13. Extending to Geometric Model • All Interactions Considered • Full Response Surface In Single View

  14. Money In The Bank • Improved Process Understanding Drives Reduced Variability • Immediate Manufacturing Savings Possible • Reduced Test Cost • Elimination Of Excess Idle Time • Unnecessary WIP/Inventory Cost Elimination • Much More Certain Planning and Scheduling Feasible • Entire Factory Throughput Can Now Be Optimized

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