IDA Ireland / PharmaChemical Ireland Symposium
The Road to Integrated Development and Manufacturing
Jacintha GriffinWyeth 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
1992 - 20031992 - 2003 20042004
20052005
20072007
20082008
20092009
Technical Transfers & Process
Optimisation
Co-Development & Clinical Trial Supplies
PDC Concept Approval
New products organization & PDCs in
Operation
Newbridge PDC Construction Start
Newbridge PDC
Opens
Pharmaceutical Development Centre (PDC) Integrated Development and Manufacturing
Business Case and Fiscal SupportsCritical 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 Charter
• Process Robustness thru “Quality by Design”- Increase Robustness, Reproducibility, Reliability and Compliance
• Co-Develop and Optimize at site of commercial manufacture
- Ensure shortest possible development time and mitigate risk of delayed launch
• Improve Product and Process Characterization- Critical Control Parameter Determinations
- Enhanced Process Ranging Studies
• Explore new technologies and innovative equipment - Lead to competitive advantage (e.g. patent extensions, speed to market)
• Flexible Capacity to respond to Pipeline Products
PDC Charter
• Integration of PAT/Data Management
• Analytical Lab to support the Development Centre- Optimization of analytical methods for pipeline and inline products
• Support manufacture of Early and Late Phase Clinical Materials
• Foster technical exchange, learning and continuity of knowledge
- Between R&D and the commercial site
- Opportunity for collaboration with Local Universities
• Improve “On Site” understanding of process prior to launch
• Extend exclusive life time of existing marketed products Patent Extensions and Lifecycle Management
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
PDC NewbridgeMulti-Purpose Multi- Product cGMP Module
MolecularMolecular ParticulateParticulate Bulk powderBulk powder Final dosage form
Final dosage form
Spectroscopic: NIR
Other chemical: Analysis to support physical characterisation (GQAD)
Spectroscopic: NIR
Other chemical: Analysis to support physical characterisation (GQAD)
Crystallographic: X-Ray 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
Crystallographic: X-Ray 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
Mechanical: Texture Analysis
Flow: Powder Rheometry
Agglomeration: Air Jet Sieving
Moisture: Loss on Drying, Water Activity
Density: Bulk and Tapped Density, Helium Pycnometry, Envelope Density
Mechanical: Texture Analysis
Flow: Powder Rheometry
Agglomeration: Air Jet Sieving
Moisture: Loss on Drying, Water Activity
Density: Bulk and Tapped Density, Helium Pycnometry, Envelope Density
Coating Layer Thickness: Terahertz Pulsed Imaging
Tablet Dimensions: Tablet Autotester
Coating Layer Thickness: Terahertz Pulsed Imaging
Tablet Dimensions: Tablet Autotester
Focus on Capability – Process Characterisation
1 – 5kg & 5 – 50kg Equipment
Process Char. Lab
LIMS SAP ERP BMS
PAT & Data Management Infrastructure
PAT ToolsPAT Tools
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
Newbridge PDC Competencies
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
CorporateR&D
Phase 2 Phase 3 CommercialPhase 0, 1
Pipeline
Pipeline
New York
PDC
Puerto RicoPDC
Newbridge
PDC
Process Knowledge 3rd Party
Puerto Rico
Newbridge, Ireland
New Products & Process Development (NPPD) and PDC Network
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 ManufacturingA 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
Build on manufacturing expertise and proven track record Tech, transfers, scale up, operational excellence
Build and deliver on business caseo Drive an integrated & innovative approach to development and
manufacturingo Focus on smart development and manufacturing excellenceo Science driving complianceo 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
Summary
Thank You
Questions?