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?