Process Robustness & Challenges to Demonstrating Compliance

Transcription

1 Process Robustness & Challenges to Demonstrating Compliance Nick Smith Head of Production & TSS 2 nd March 2017

2 95% Thomas Eldered 5% Management Headcount : GMP facilities Cobra s Structure Cobra Biologics Holding AB Board of Directors Thomas Eldered (Chairman) Peter Coleman (CEO) Carl Johan Spak Carl Johan Sundberg Elisabeth Lindner Gesar Wang Cobra Biologics AB Cobra Biologics Matfors AB Cobra Biologics UK Ltd Södertälje, Sweden 110 employees Matfors, Sweden 60 employees Keele, United Kingdom 100 employees

3 Cobra s History

4 Our Facilities Matfors, Nr. Sundsvall, Sweden Keele, Nr Manchester, United Kingdom Södertälje, Nr. Stockholm, Sweden

5 Site by Site Capability Södertälje: Mammalian Cell / MAB / Biosimilar 19 year track record, advanced facility, 2 GMP suites Comprehensive analytics and cell line development capability Process development to 250L SUB Developing capability in perfusion production 1000L & 250L disposable SUB for commercial capacity FastXpress mab development offering Keele: Gene Therapy 18 year track record 50L stainless steel fermenter 50L microbial disposable SUB HQ DNA / process development and analytics AAV/lenti and adenovirus process development and GMP Matfors: Fill/ Finish and Large Scale Microbial 20 year track record for clinical and commercial supply with 600L microbial GMP capacity Aseptic fill/ finish facility including lyophilisation capability Expansion space for fill/finish or bio-production

6 Our Product Categories Cobra has a unique global track record in all product categories

7 Cobra s Gene Therapy Service Offerings Plasmid DNA + GMP grade Plasmid DNA Bacterial cell Clinical Use Small amounts of plasmid DNA, carrying genes of interest, are mixed with bacterial cells Bacterial cells take up the DNA. As the bacteria grow and divide they make lots of copies of the plasmid DNA. Plasmid DNA is purified away from the bacterial contaminants, and formulated into the Gene Therapy medicine. GMP grade Plasmid DNA HQ grade Plasmid DNA Or can be used as a starting material for Viral Vector production. + Plasmid DNA (minimum 3 plasmids) GMP grade Viral Vectors Cultured mammalian cell Clinical Use Purified plasmid DNAs, carrying the genes for viral vector generation, are mixed with cultured mammalian cells The cells take up the DNA and the genes on the plasmids are switched on. These plasmid delivered genes allow the cells to make lots of viral vector particles. Viral vector particles are purified away from the cells and plasmids, and formulated into the Gene Therapy medicine.

8 Cobra s Revenue Growth since % group revenue growth since 2011

9 Services, Project Management and Quality

10 Our Global Customers Successful completion of > 450 batches Worked with > 100 customers Customers located in 19 countries across 5 continents 31 Different Customers at Keele

11 Global Manufacturing Landscape for Viral Vectors and Plasmid DNA CDMO Landscape Only 5 companies offer dedicated contract manufacturing services (no internal products) for clinical production [Roots Analysis 2016 Viral Vectors and Plasmid DNA Manufacturing Market ]

12 Demonstrating Compliance Through Documentation GMP Documentation is: Material that provides official information or evidence or that serves as a record An essential part of a Quality Assurance system A detailed picture of what a manufacturing function has done in the past, present and provides a basis for planning the future The documentation: Provides instruction on how to perform a task Records what was performed and by which individual Provides evidence that a procedure was performed correctly Ensures traceability throughout batch production

13 The Inputs

14 Equipment

15 Equipment Fit for Purpose Calibrated and Qualified across the process range Impact of failure on review Breakdowns Cleaning Frequent and aggressive Bioburden control Difficult to validate Product changeovers not replicated Analytical method validation Time & Cost to customer Client confidentiality Risk assess proximity to patient Closed System Manufacture Disposable technology Biological Containment

16 Process

17 Process All aspects of production approved by the client Critical Process Parameters not fully defined at Clinical Phase Subtle changes can have significant effect: Order of addition Scale-up Mixing Dynamics Addition rates Application of platform process to the product Single batch requirement Unexpected performance: Growth Behaviour Yield Additional Process Steps

18 People

19 People Process GMP Framework for decision making Training & Process understanding Clean Room Environment Risk of cross contamination Single Process Policy Gowning Qualified Aseptic Technique Recruitment and Retention Limited skilled GMP operators in UK GMP & Process Development dichotomy Biologics Process Flexibility & Shifts Availability Access to Support Staff QA QC Stores Engineering

20 Materials

21 Materials Supplier Quality Assurance Customer Specific Requirements Changes to standard materials Sourcing appropriate / equivalent grades Coordination & Segregation Preventing mix-up Contingency Additional / repeat process steps Custom Builds / Closed Systems Sourcing for single manufactures No surprises!

22 Environment

23 Environment Facility Cleaning Process Impact & Validation Trending Gowning Qualification Maintaining Segregation Cross flows of multiple processes Starting Materials Finished Product Waste

24 Management

25 Management Approved Suppliers Documented Training Specific Process Instructions Integration with Quality Assurance Systems: Change Controls and Deviations Client discussion / approval Impact Assessment v registered particulars Dedicated Process Teams Scheduling client specific Process Equipment In-Process Support Executing multiple new processes in parallel across different disciplines

26 Summary Processes and systems are complex Changes and events will happen Compliance is demonstrated by documented evidence: Quality Systems Data Integrity: A attributable to the person generating the data L legible and permanent C contemporaneous (recorded in real time) O original record (or true copy ) A accurate

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