Implementation Of 2000 L Sub And Disposable Clarification System


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Implementation of new single use bioreactor system

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Implementation Of 2000 L Sub And Disposable Clarification System

  1. 1. Implementation of 2000L SUB andDisposable Clarification System in Existing cGMP Facility Dave Wolton CMC Biologics 2011-10-25
  2. 2. Overview• CMC Biologics• Why is the 2000L a game changer?• Integration into Existing Facility• Defining the Bioreactor Process• Facility Design Challenges• Disposable Harvest System• Lessons Learnt 2
  3. 3. CMC Biologics Target Pre- Commercial & Lead Tox Phase I Phase II Phase III tox Production ID CMC Biologics Contract Manufacturer of Biological Therapeutics utilizing MAMMALIAN & MICROBIAL CELL CULTURE TECHNOLOGIES• Cell-line Development – CHEF1™ technology• Upstream/Downstream – process development and manufacture• Analysis, Characterization, Formulation, Quality and Regulatory
  4. 4. Background to why I believe the2000L is a game changer• 13 years at contract manufacturer in Slough 2000L scale• 6 years producing Enbrel in a 6 x 12,000L plant• 1 year designing 12 x 1000L SUB plant • Approximately 1 million Euros spent on basis of design• Moved to CMC 2 years agoCONFIDENTIAL 4
  5. 5. Blockbuster ‘in market supply’potential of the 2000L SUB factory Output from model = 2 x 12,000L stainless plant – Plant runs for 300 days per year – Protein A Cycles per batch approx. 4 – Harvest two reactors every 2 days – Assumed product campaigns are the norm – Cell culture only work days 5
  6. 6. Plants of the future 6 x 12,000L x 2,000LxDisposable 12 12 2,000L Disposable Lean design stainless Conventional design 6
  7. 7. Plants of the future Reactor hall 15M x 15M 7
  8. 8. Copenhagen 2000L SUBImplementation and proof of concept
  9. 9. 2000L SUB• 2000L capacity retrofitted to a 100L stainless steel suite 9
  10. 10. Aim of the project• Increase US/DS capacity to match launch/commercial production (MAB): 2000L• Integrate into existing facility without affecting current clinical manufacturing• Minimize limited company recourses • Project used 1 Engineer and two validation resources• Meet cGMP requirements – EMEA, FDA 10
  11. 11. 2000L SUB in 100L SS facilityMicrobial CCI2x 1500L 2x 750L CCII 100LCCIII300L 11
  12. 12. Stainless Steel SIP Automatic valves CIP DCSHPW 70 elastomers 12
  13. 13. Disposable Bioreactor• Minimize limited company recourses SIP• Low level of atomization CIP• Off the shelf• High flexibility HPW• Waste – Supported by DCS existing infra-structure at CMC Biologics Waste 13
  14. 14. Defining the Bioreactor Process 14
  15. 15. Project Plan 7 months from start to finish Right. On time. 15
  16. 16. Vendor: • Security of supply • Market leader in number of units sold • Back up in both USA and Europe • We already use their single use mixers, 100L, and 500L SUBs • Willingness to negotiate a bag supply agreement • Track record in supplying disposables • Conventional design • Compact storage • Wide choice of control systems 16
  17. 17. Vendor: EZ controller• Wheel in wheel out seed reactor concept• Simple• Robust• Large number of units sold• Fast to set up, train on and validate• Compact (can be mounted on the SUB)• Cost effective to have multiple units on multiple SUB’s 17
  18. 18. Factory Acceptance Testing 18
  19. 19. Installation 19
  20. 20. Installation Reception as it was 20
  21. 21. Installation 21
  22. 22. Installation Reception as it looks now…. 22
  23. 23. Engineering Run - Inoculation XG2Cb 23
  24. 24. 2000L SUB data• The light blue datapoints represent the 2000L SUB• The other data is from 500L SUB runs of the same product 24
  25. 25. Disposable Harvst System 25
  26. 26. Integrated 2000L depth filter system 26
  27. 27. Lessons Learnt• Decide on controller early – This will impact timelines and complexity• Agree who mounts the control system and where it will be mounted• Do a cost benefit analysis on the seed strategy• Take into account fabrication and shipping costs/time• Be careful in regards vessel orientation and hose location 27
  28. 28. Summary• Slide from Johannes R. Roebers, PhD 28
  29. 29. Thanks to…• Andreas Mark Arnung, CMC Biologics• Christian Skjødt, CMC Biologics• Esben Eggertsen, CMC Biologics• Gustavo Mahler, CMC Biologics• Henrik Knudsen, CMC Biologics• Jakob Ravnsborg, CMC Biologics• Johannes R. Roebers PhD, Elan• Mads Laustsen, CMC Biologics• Martin Oscar Miret Hattel , CMC Biologics• Martin Kelly, Thermo Scientific• Ronni Glenn Refstrup Hansen , CMC Biologics 29
  30. 30. CONFIDENTIAL 30
  31. 31. 31