How to merge R&D dream and GMP reality PAS-X Process Development in Novartis Technical R&D 11th PAS-X User Group Meeting, May 3rd, 2013, Morristown, NJ Patrick Drumm (for Dr. R. Leu Marseiler), Novartis Pharma PAS-X Introduction at Novartis TRD Background  PAS-X widely used in Novartis commercial sites  Introduction of Supply Chain Management within Technical Research and Development (TRD): • SAP as ERP • PAS-X as MES in Pharmaceutical&Analytical Development (PHAD)  first introduction in R&D environment within Novartis  PHAD Pilot Plants CH: • 2 Pilot Plants (Steril, liquid & topical dosage forms/solid dosage forms)  GMP batches for clinical supplies  High turnover of products due to changing pipeline, low re-supply rate  nonGMP batches for process development and scale up 2 Dr. R. Leu Marseiler, Novartis Pharma AG What our Formulation Experts dream of...... Freedom & Flexibilitiy Just do it! Short Lead Time Easy Documentation 3 Dr. R. Leu Marseiler, Novartis Pharma AG How GMP reality looks like................ Standardization and Control QA Approval for MBRs Material Master Data SOPs Change Control Cleaning Rules 4 Dr. R. Leu Marseiler, Novartis Pharma AG Material Reconciliation Calibration Ranges The Key Question For succesfull introduction in R&D QA Approval for MBRs Material Master Data SOPs Change Control Cleaning Rules Material Reconciliati on Calibration Ranges How to benefit of PAS-X for clinical batches... ......without compromising flexibility for technical batches? Freedom & Flexibility Short Lead Time Easy Documentation 5 Dr. R. Leu Marseiler, Novartis Pharma AG The Answer PAS-X Feature Package Process Development Clinical Technical Technical light Development Studies Enhanced Parameterization 6 Dr. R. Leu Marseiler, Novartis Pharma AG DoE Designer Technical Light Batches Replace Paper&Pencil by Scanner&PAS-X  First feasibility trials in early development  Forecasting and planning based on «dummy material» • No real Bill of Material pre-defined • Drug substance and Excipients needs for several trials within BOM  Development Studies within PAS-X to define single trials  Just Recording • No MBR => full flexibility  All GMP relevant data, some process data is collected: • Material consumption => inventory adjusted • Equipment allocation => equipment status, cleaning rules controlled • Equipment attribute => ensure equipment is used in calibrated range 7 Dr. R. Leu Marseiler, Novartis Pharma AG Technical Batches Simplify Series of Technical Trials  Process optimization and Scale up trials  Bill of Material pre-defined  MBR or GMBR&PVL • Reduced approval workflow (QA not involved) • Use of DoE Designer for a series of trial: 1 DoE 22 A B (1) - - a + - b - + ab + + = 1 GMBR + 4 PVLs = 4 pMBRs PVL1 PVL2 PVL3 PVL4 Parameter A 50° 60°C 50° 60°C Parameter B 10 kN 15 kN 10 kN 15 kN  All GMP and process data is recorded 8 Dr. R. Leu Marseiler, Novartis Pharma AG Clinical Batches Facilitate MBR design for high turn-over of products  Clinical Supply batches fully GMP compliant  Bill of Material pre-defined  MBR or GMBR&PVL • approved by QA • Process specific GMBRs combined with product specific PVLs PVL1 PVL2 PVL3 PVL4 Target Material A B C D Drug Substance NVS1 NVS1 NVS2 NVS3 Excipient 1 Excipient 2 Excipient 3 Lactose Starch Mg stearate Lactose Starch Mg stearate Starch Mannitol Mg stearate Lactose Mg stearate Mixer Tumble A Tumble A Tumble B Tumble A Fill weight 125mg 250mg 150mg 300 mg 9 Dr. R. Leu Marseiler, Novartis Pharma AG PAS-X plus PD offers......... The Right Solution for Each Batch Development Phases Standardization&Control Technical light Technical Clinical Freedom&Flexibility The benefits of an MES ......... .......without limiting the flexibility for R&D 10 Dr. R. Leu Marseiler, Novartis Pharma AG