implementation of 2000 l sub and disposable clarification system
DESCRIPTION
Implementation of new single use bioreactor systemTRANSCRIPT
Implementation of 2000L SUB and
Disposable Clarification System in
Existing cGMP Facility
Dave Wolton
CMC Biologics
2011-10-25
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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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
Target
& Lead
ID
Pre-
tox Tox Phase I Phase II Phase III
Commercial
Production
CMC Biologics
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
– 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
= 2 x 12,000L stainless plant
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Blockbuster ‘in market supply’
potential of the 2000L SUB factory
Output from model
Plants of the future
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6 x 12,000L stainless
12 x 2,000L Disposable Conventional design
12 x 2,000L Disposable Lean design
Plants of the future
7
Reactor hall 15M x 15M
Copenhagen 2000L SUB
Implementation and proof of
concept
2000L SUB
• 2000L capacity retrofitted to a 100L stainless
steel suite
9
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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2000L SUB in 100L SS facility
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Microbial 2x 1500L
CCI 2x 750L
CCII 100L
CCIII 300L
Stainless Steel
12
SIP
CIP
HPW
Automatic valves
DCS
70 elastomers
Disposable Bioreactor
• Minimize limited
company recourses
• Low level of
atomization
• Off the shelf
• High flexibility
• Waste – Supported by
existing infra-structure
at CMC Biologics
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SIP
CIP
HPW
DCS
Waste
Defining the Bioreactor Process
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Project Plan
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7 months from start to finish
Right. On time.
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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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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Factory Acceptance Testing
18
Installation
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Installation
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Reception as
it was
Installation
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Installation
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Reception as
it looks now….
Engineering Run - Inoculation
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XG2Cb
2000L SUB data
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• The light blue
datapoints
represent the
2000L SUB
• The other data is
from 500L SUB
runs of the same
product
Disposable Harvst System
25
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Integrated 2000L depth filter system
Lessons Learnt
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• 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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Summary
• Slide from Johannes R. Roebers, PhD
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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CONFIDENTIAL 30
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