Cell Therapy Catapult Manufacturing Solutions for cell-based ATMPs. A presentation by Head of Process Development, Sarah Callens Nov 2013
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Cell Therapy Catapult Manufacturing Solutions for cell-based ATMPs. A presentation by Head of Process Development, Sarah Callens. Nov 2013

Cell Therapy Catapult Manufacturing Solutions for cell-based ATMPs. A presentation by Head of Process Development, Sarah Callens. Nov 2013

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Cell Therapy Catapult Manufacturing Solutions for cell-based ATMPs. A presentation by Head of Process Development, Sarah Callens Nov 2013 Presentation Transcript

  • 1. Cell Therapy Catapult Manufacturing Solutions for cell-based ATMPs Quality and Manufacturing Solutions for Advanced Therapies Workshop Sarah Callens Head of Process Development November 2013 Sarah.callens@ct.catapult.org.uk http://ct.catapult.org.uk/  Catapult is a Technology Strategy Board programme
  • 2. 2 •  Process Development team and capabilities •  Process Development equipment •  How to develop a manufacturing strategy
  • 3. CTC Capabilities: Process Development 3 Process Development Resourcing •  10 FTE expanding to 15 FTE by April 2014 Capabilities •  QbD, experimental design, TPP, risk analysis, device design control, bioreactor design, automation and software design, CoG reduction •  iPS culture, directed differentiation, decellularisation, encapsulation, large-scale cell culture, cell banking, 3D scaffold production, suspension culture, GMP production experience •  Process development for autologous immune therapies, closed processing, large scale adherent and suspension cultures, novel process development for 2D and 3D therapies.
  • 4. Process Development Capability Primary Recovery Akta TFF SciLog TFF 15 FTE Rocking platform Cubian XC 1.7M budget 2013 Vi-CELL Stirred platform Automated Quantum® Fill Finish Manual Peregrine In Process Control Cell Expansion KSep
  • 5. Starting material and IPC Analysis Cubian XC Peregrine 5 xCelligence MP
  • 6. Cell separation, concentration, wash and formulation Sepax II Smart Max 6
  • 7. Cell expansion 7 Rocking Motion Platform Disposable Stirred Platform Quantum® Hollow Fibre
  • 8. Primary Recovery 8 SciLog TFF GE Akta Crossflow KSep
  • 9. Filling Lines L1 Automated Filling Line 9 M1 Manual Filling Line
  • 10. Developing a Manufacturing Strategy What does the product need to do? Generate Target Product Profile (TPP) (Start with clinical need) •  Composition and dose •  Cell types, forumulation etc •  Function (may include handling properties or physical characteristics •  Immunomodulatory, targeting, angiogenic, porosity, tensile strength, surgical implementation •  How much, how often, at what cost •  Expiry and cold chain, facility constraints •  Business Aspects •  Logistics 10
  • 11. Think about what data needs to be generated Input-Output (IPO) Diagram Inputs Fixed Factors - constants PROCESS (Cell Harvest Step ) Environmental – outside of control Outputs
  • 12. Use TPP requirements to design experiments: Experimental Planning Experimental Objective Screening Optimisation Many factors Few levels Fewer factors More levels Objective Assessment Scale-up/ TechTransfer Data Fit for purpose? Bioprocess Development entails a progressive approach to Goal Attainment Unit Operations within a Bioprocess do not reside as stand alone operations within a Bioprocess Train The cell product and the process by which its produced cannot be separated – the product is the process Experimental Planning requires a degree of rational progression to successfully address the goal: producing a robust, efficacious and economically viable product
  • 13. DoE Process: From Screening to Optimisation e.g. cell harvest step Time in culture Vessel Type Detachment Agent Hold Time Buffer Wash Surface Type Screening Hold Time Centrifugation Parameters Optimisation Wash Method Feed frequency Wash Method Centrifugation Parameters Choose factor ranges Determination of relevant factors Adjust factor ranges accordingly Determination of optimal settings
  • 14. Key Process Parameters determined by Risk Assessment 14 Ishikawa e.g. cell harvest step Machine Measurement Environment CO2 Flow rate C C % CO2 Temp of cells N Time X Laminar flow C C Ambient temp N Media warming (time@temp) C Detachment Final vol wash of cells C buffer X Hold time N Room temp C DPBS Vessel type X (diffusion) Confluence Setting Surface type X Detachment Agent conc. Vol of detach. agent X X 5% CO2 C X Media C Change method Sampling Material Location Amount C C Methods Microscope C Setting Daily Temp Monitoring C Calibration of pipettes C Inc door open time Temp of inc. C % CO2 PROBLEM STATEMENT N Cell Yield at 70% Confluency Final cell wash method (# of X washes) Feed X frequency Handling Validation of confluency C Detachment time X Rinse of surface after detachment X Recovery N process Sample mixing C People C Different C operators Time C served C = Constant N = Noise X = Experimental
  • 15. Interactive map of critical parameters and their limits following experimentation • Operating Space C = critical • Acceptable space/Design space NC = non-critical Minimum Seeding Density Max Incubation time Feeding frequency Volume of Detachment Agent Dilution of Detachment Agent Temperature of Detachment Time of Detachment Recovery Volume Protein in Recovery Buffer Post-Detachment Holding Time C C 5E3/CM2 CONTROL: 3-4 days ACCEPTABLE: 6 Days C 3 DAYS NC 0.06ml/cm2 NC CONTROL-NEAT ACCEPTABLE- 1:2 NC 18-37 C C CONTROL- min 40min ACCEPTABLE – max 120min NC 0.06ml/cm2 C 2% NC Up to 180min
  • 16. Select manufacturing strategy that will meet requirements of TPP and output of CPP 16
  • 17. Researchers Industry Cell Therapy Catapult NHS Investment   Cell Therapy Catapult NIHR Biomedical Research Centre, 16th Floor Tower Wing, Guy's Hospital Great Maze Pond, London, SE1 9RT DDI: +44 (0) 207 1883428  Mob: +44(0)7891 295131 chris.herbert@ct.catapult.org.uk Catapult is a Technology Strategy Board programme