Implementation of new single use bioreactor system

1. Implementation of 2000L SUB and
Disposable Clarification System in
Existing cGMP Facility
Dave Wolton
CMC Biologics
2011-10-25

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
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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. Background to why I believe the
2000L 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 ago
CONFIDENTIAL 4

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
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6. Plants of the future
6 x 12,000L x 2,000LxDisposable
12 12 2,000L Disposable
Lean design
stainless Conventional design
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7. Plants of the future
Reactor hall 15M x 15M
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8. Copenhagen 2000L SUB
Implementation and proof of
concept

9. 2000L SUB
• 2000L capacity retrofitted to a 100L stainless
steel suite
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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
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11. 2000L SUB in 100L SS facility
Microbial CCI
2x 1500L 2x 750L
CCII
100L
CCIII
300L
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12. Stainless Steel
SIP
Automatic valves
CIP
DCS
HPW
70 elastomers
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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
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14. Defining the Bioreactor Process
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15. Project Plan
7 months from start to finish
Right. On time.
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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
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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
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18. Factory Acceptance Testing
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19. Installation
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20. Installation
Reception as
it was
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21. Installation
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22. Installation
Reception as
it looks now….
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23. Engineering Run - Inoculation
XG2Cb
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24. 2000L SUB data
• The light blue
datapoints
represent the
2000L SUB
• The other data is
from 500L SUB
runs of the same
product
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25. Disposable Harvst System
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26. Integrated 2000L depth filter system
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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
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28. Summary
• Slide from Johannes R. Roebers, PhD
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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
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30. CONFIDENTIAL 30

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