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IDA Ireland / PharmaChemical Ireland Symposium The Road to Integrated Development and Manufacturing Jacintha Griffin Wyeth Newbridge September 23rd 2009 Overview The Road to Integrated Development & Manufacturing • From technical transfer to Co-development • Pharmaceutical Development Centre (PDC) business case • PDC Newbridge – Capability, facility and approach to integrated development & manufacturing • Development and Manufacturing Model - Future Opportunities and Challenges Wyeth Newbridge The Road to Integrated Development & Manufacturing Newbridge PDC Newbridge PDC Construction Start 2009 New products organization & PDCs in Operation PDC Concept Approval Co-Development & Clinical Trial Supplies Technical Transfers & Process Optimisation 1992 - 2003 2004 2008 2007 2005 Opens Pharmaceutical Development Centre (PDC) Integrated Development and Manufacturing Business Case and Fiscal Supports Critical Supports in Justifying Business Case for Development centre: • Proven technical capability of supporting a large portfolio of solid dosage products • Demonstrated capability in collaborating with corporate R&D - Co-development • Collaboration with the IMB for rapid application, audit and receipt of IMP licence • Process optimization for marketed product portfolio - “Quality by re-Design” • Changing regulatory environment – impact of ICH Q8, 9, 10 Government, IDA mandate and support • R&D Tax Credit System & capability grants • 12.5% Corporation Tax • IP Royalty Scheme PDC Charter and value proposition PDC Newbridge Multi-Purpose Multi- Product cGMP Module Pilot Scale 5-50kg • 1/10th the commercial scale of pipeline products Small Scale (<5kg Suite) • ‘Smart Development’ Smaller Batches - Higher Velocity / Throughput • Supports API Cost and Supply Constraints Full Scalability to pilot and commercial scales • Process Characterisation Laboratory • • Active and Excipient Functional Characterisation Dedicated Analytical Development Laboratory Flexible and Modular Design • • • Multiple Product Capability Flexible Containment to handle potent compounds “Future Proofed” for Next Generation Technologies PAT/Data Management Infrastructure • Process Analytical Infrastructure for Real Time Acquisition, Aggregation, Analysis of Data Focus on Capability – Process Characterisation Molecular Spectroscopic: NIR Other chemical: Analysis to support physical characterisation (GQAD) Particulate Crystallographic: XRay Powder Diffraction (with Controlled Humidity Chamber) Microscopic: Scanning Electron Microscopy, Optical Microscopy, Image Analysis Thermal: Differential Scanning Calorimetry, Thermogravimetric Analysis Micromeritic: Specific Surface Area, Dynamic Vapour Sorption, Particle Size Analysis Bulk powder Final dosage form Mechanical: Texture Analysis Coating Layer Thickness: Terahertz Pulsed Imaging Flow: Powder Rheometry Agglomeration: Air Jet Sieving Moisture: Loss on Drying, Water Activity Density: Bulk and Tapped Density, Helium Pycnometry, Envelope Density Tablet Dimensions: Tablet Autotester PAT & Data Management Infrastructure Process Char. Lab LIMS SAP ERP PAT Tools 1 – 5kg & 5 – 50kg Equipment BMS Newbridge PDC Competencies Cross Functional Team with Qualifications, Subject Matter Expertise and Practical Experience in: • Material Science • Powder Properties, Spectroscopic Techniques • Formulation Design • Pharmaceutics, Drug development, Pharmacokinetics • Process Design & Process Engineering • Process development • Analytical Method Design and Development • Spectroscopic Techniques, QbD for methods • Scale-up Expertise, Operational excellence and Lean manufacturing methodologies • Process Analytical Technology and Chemometrics expertise • IT, Automation and Data Management • Software Programming, Automation and Control Systems • Quality and Compliance • Regulatory understanding and application of CFR, GMP and ICH Q8, Q9 and Q10 Organisational structure to deliver success New Products and Process Development (NPPD) • Accountable for all new product activities from Proof of Concept (PoC) Key operating principles: • “Quality by Design” and “Quality Risk Management” principles embedded • API and Drug product accountabilities • Broad scope – clinical relevance and manufacturing optimization • Smart Development - Do more with less API using QbD and DoEs • Drive Finished Product dosage to support standardized technology platforms • PDC network part of NPPD New Products & Process Development (NPPD) and PDC Network Newbridge PDC Pipeline Newbridge, Ireland Corporate R&D New York PDC Process Knowledge 3rd Party Pipeline Puerto Rico PDC Phase 0, 1 Phase 2 Phase 3 Puerto Rico Commercial Building blocks for integrated Development & Manufacturing Using Quality Risk Management techniques to drive the level of development activities required to yield the highest level of scientific knowledge Understand inputs - physical characterisation techniques Structured development programme - Understand Design space and interdependencies through DOEs Data management infrastructure - design allows for the ability to Acquire, Analyse, Archive and Report Product and Process Data Advanced chemometrics and statistical modelling to interrogate and understand data Process Analytical Technology (PAT) for real time monitoring, prediction and control of quality attributes Elimination of science of scale through knowledge management, model creation & Management Regulatory filing (Design & Control space) and elimination of post approval changes PDC – Co-location with Manufacturing A Win - Win Development co-located with manufacturing at commercial site • Enhanced technical expertise to support both marketed and pipeline portfolios • Seamless knowledge transfer from late stage development through to commercial • Manufacturing requirements and input earlier into development programme • Influences standardized technology platform selection • Technical training and site upskilling • Reduction in regulatory complexity – Learn before filing • Deployment of PAT “with a purpose” – Pull not Push Looking to the future Future Opportunities • Leverage from Competence Centres/Clusters – Solid state Pharmaceutical cluster (SSPC) etc • Build RD&I reputation – IP, publications, conferences • Business Process Innovation • RTR & Continuous Manufacturing Industry Challenges • Availability of personnel with cross functional skills • Alignment and harmonisation of regulatory requirements of EMEA / Japan / FDA & other global markets Summary Build on manufacturing expertise and proven track record Tech, transfers, scale up, operational excellence Build and deliver on business case o Drive an integrated & innovative approach to development and manufacturing o Focus on smart development and manufacturing excellence o Science driving compliance o Simple PAT solutions Grow a highly skilled, cross functional Team Diverse backgrounds –formulation & process development, automation, statistics, chemometrics, analytics & engineering Overall result: Enhanced process knowledge -Defined targets & ranges for CPP and CQA o Enhanced robustness, reduced COGs, elimination of scale up issues Thank You Questions?