Product Quality beyond Compliance Case Study: Continuous Manufacturing

Transcription

1 Product Quality beyond Compliance Case Study: Continuous Manufacturing IFPAC Conference, Washington D.C. Yanxi Tan Cain, Ph.D. Regional Head Novartis Pharma Quality Operation January 27th, 2015

2 Disclaimer This presentation is based on publicly available information. These slides are intended for the personal use of the audience. These slides are not intended for wider distribution outside the intended purpose without presenter approval. The content of this slide deck is accurate to the best of the presenter s knowledge at the time of production. 2 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

3 The Journey of Quality Beyond Compliance A Quality Journey was started... Quality System provides the framework Managing Quality Common quality system & standards across all Novartis divisions Making Medicine Focus on our products and how we make medicine Continuous Improvement Manufacturing Strategy/ Quality Strategy; Quality by Design Competitive advantage Sustainable and reliable supply network of high quality products 3 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

4 Quality Strategy Anticipating long-term needs with a strong focus on the quality culture Quality Beyond Compliance Continuous Improvement, Competitive Advantage People, organizational capability, training Quality Culture Products, process, and technology Quality systems and tools Cooperation and alignment External engagement Managing Quality and Making Medicine 4 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

5 Developing Knowledge over Product Lifecycle Continuous Manufacturing Supply patients with quality products right first time and every time, efficiently and safely Offer in depth process understanding and knowledge to manage the risks through product lifecycle Deliver quality product through precise sysmatic process control and confirmed through PAT Reduce complexity of the processes (less steps) and product lifecycle Ensue product quality at dosage level vs. batch Patient needs Truly achieve product quality by design, rather by analysis Quality Cost 5 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Compliance Business Use Only

6 Concept for Continuous Manufacturing The process is the product! All continuous unit operations Total integration, coupled end-toend Systems approach Plant wide control strategy 6 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Compliance Business Use Only

7 Continuous Batch Quality Beyond Compliance Process Transformation Batch Facility 1 & 2 Mostly step based Separation of DS & DP steps and sites Large fragmented footprint, high CAPEX Long lead times Facility 3 Continuous Simultaneous inlet and outlet of materials Intensified processes with shortened lead times (hours vs. months) Increased supply chain flexibility Facility 1 Filter 1 Membrane Filter 2 Separator Reactor 1 LLE Crystallizer Reactor 2 Reactor 3 Dehydration Column Reactor/ Waste Waste Waste Crystallizer Waste Waste Reduced plant footprint, lower CAPEX Dryer 1 Extruder Injection Mold Tablet Coater DP (Tablets) Qualtiy quantum leap by higher level of process control 7 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Compliance Business Use Only

8 Process Transformation: Continuous Manufacturing Continuous Manufacturing is based on Process Intensification which allows more precise process control Maximised material processing in the smallest process space, for example: 8 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

9 10 cm Process Transformation: Continuous Manufacturing Intensification made easy with simultaneous inlet of raws and outlet of products Corning Continuous conversion of materials = flow processing = Continuous Manufacturing Flow=Rate Control is key! 9 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Compliance Business Use Only

10 Key Aspects of Continuous Manufacturing A process principle that is characterized by simultaneous inlet and outlet of materials, creating/modifying/transforming materials at a controlled rate over time. Offers opportunities to yield better quality at shorter lead times, smaller plant footprint, little to no scaleup and reduced number of unit operations as it is an enabler for transformations of extreme kinetics (fast, hazardous) and takes out many corrective steps, hence streamlines the overall process chain. As a consequence process development requires kinetic understanding and process characterisation 10 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

11 Magnitude of Technical Challenge New process technologies for most unit operations New approaches for end to end integration of process technologies New development roadmaps for projects New screening tools to match projects and technologies New process control strategies New quality and regulatory pathways New HSE strategies 11 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

12 Role of PAT in Continuous Manufacturing PAT enables one half of CM control strategy Online, inline, at-line, offline > faster is better Predictable and reliable response time is key Non-destructive principles if obtainable Some parameters are directly not measurable and require indirect measurements (surrogate test) Challenges: Impurities, Dissolution, Micro, Polymorphism 12 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

13 New Quality Paradigm Lead Successful Implementation Quality cannot be tested into the product, i.e., quality should be built in by design. (ICH Q8) CM will bring us there... Batch definition Start product collection Material traceability in CM train Release decision Process validation 13 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

14 Ensure Fast Adoption: Build Confidence! Stepwise move from batch release concept to advanced concepts in sync with implementation timing 1. Release on basis of sampling and testing for clinicals and to develop correlation between in-process data (PAT and model based) and end-product testing data 2. Escalate parameters where this correlation is known and switch accordingly 3. Full implementation of QbD/PAT/advanced control during commercial phase after data body has been generated 14 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

15 CM Changing the Way Medicines are Made Quality beyond compliance Ensure patients rapid access to breakthrough therapies Offer in depth process understanding and knowledge to manage the risks through product lifecycle Truly achieve product quality by design, rather by analysis 15 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only

16 Acknowledgements Dedicated and innovative Novartis CM Technical, Quality and Regulatory scientists Continuous Manufacturing Joint Industry/Regulator/MIT White Paper working groups 16 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Compliance Business Use Only

17 Q&A 17 IFPAC Conference Yanxi Tan Cain January 27th, 2015 Product Quality beyond Complaince Business Use Only