flexible facility success
TRANSCRIPT
Flexible facility successCase study of 12 flexible facility biopharm projects
Frank NygaardMay, 2015
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Content
The 12 projects – common denominators
The 12 projects – the data set
Process design
Facility design and manufacturing strategy - campaign versus concurrent manufacturing
Facility design
Single-use implementation
Capacity expansion strategies
Flexible technology integration
Summary
The 12 projectsCommon denominators
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Single-use technology: Enabler for flexible manufacturing
• Decouples the process from the building• No complex distribution matrices as connections are flexible• Media and buffer supply is configured to the given process• Can start with only 500L bioreactor train and expand rapidly
• 2000L footprint is not drastically larger than 500L footprint
Design basics
• NNE Pharmaplan Bio on demand™ with flexibility as key driver • Facility designs are for multiproduct manufacturing• Single-use bioreactors utilised for mammalian fed-batch cell cultivation• Other process and support systems may be single-use, stainless steel or hybrid systems
The 12 projectsThe dataset
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Basic of design Location
#1 2011 China
#2 2012 Taiwan
#3 2012 Russia
#4 2012 China
#5 2012 Denmark
#6 2013 China
#7 2014 Germany
#8 2014 Brazil
#9 2014 India
#10 2014 Brazil
#11 2015 Malaysia
#12 2015 China
Pilot(3)
Launch (3)
Commercial(6)
Manufacturing scope
Basis for data evaluation
Process design
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Model processes for design• “Protein”: 58% (incl. mAbs)• mAb platform: 42%
Batch size• Pilot scale SUB: 500 – 1000L• Launch scale SUB: 1000 – 2000L• Commercial scale: 2000L 1)
Manufacturing strategy• Campaign manufacturing: 83%• Concurrent manufacturing possible: 17% 2)
Facility Design
Process design
SUB size
SUBs per line
#1 Launch “Protein” 2000L 1x
#2 Pilot “Protein” 500L 2x
#3 Launch mAb 2000L 2x
#4 Commercial mAb 2000L 4x
#5 Pilot “Protein” 1000L 4x
#6 Launch mAb 1000L 2x
#7 Commercial “Protein” 2000L 6x
#8 Commercial mAb 2000L 4x
#9 Commercial “Protein” 2000L 2x
#10 Pilot mAb 1000L 1x
#11 Commercial “Protein” 2000L 2x
#12 Commercial “Protein” 2000L 7x
1) “Scale out” of SUBs to increase batch size included in 29% of commercial designs2) Concurrent: Manufacturing of different products in cell culture possible at the same time
Facility design and manufacturing strategyCampaign versus concurrent manufacturing
• Strategic use of manufacturing strategy in the facility design
• Campaign-based manufacturing• More upstream lines than downstream
• Concurrent-based manufacturing • Less upstream lines than downstream
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Downstream DownstreamUpstream
Downstream(1 week)
Cell culture(3 weeks)
DownstreamUpstream Upstream
Facility design
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Construction design• 100% stick build (with modular construction evaluated in 17%)
Process design• 92% traditional design with seed lab, cell culture, initial and final
purification• 8% “Ballroom” concept (with shared cell culture and purification)
Cleanroom classification• Seed lab Class C (Iso 7)• Cell culture Class D (Iso 8)• Initial purification (pre-virus) Class C (Iso 7) or Class D
(Iso 8)• Final purification (post-virus) Class C (Iso 7)
Single-use implementation
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Upstream• Bioreactor: 100%• Harvest clarification: 66%
• Media preparation: 75%• Media hold: 92%
Downstream• Intermediate product hold: 92%• Process equipment: 17%
• Buffer preparation: 75%• Buffer hold: 92%
1) SU: Single use chromatography and UF/DF skids not considered
Facility design
Total capacity
Technology 1)
#1 Launch 2x 2000L SU
#2 Pilot 2x 500L SU
#3 Launch 2x 2000L SU
#4 Commercial 4x 2000L SU
#5 Pilot 4x 1000L SU
#6 Launch 2x 1000L SU
#7 Commercial 6x 2000L Hybrid
#8 Commercial 12x 2000L SU
#9 Commercial 4x 2000L Hybrid
#10 Launch 1x 1000L SU
#11 Commercial 8x 2000L Hybrid
#12 Commercial 14x 2000L Hybrid
Capacity expansion strategies
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Equipmentswap
Drop blockFitting out
Capacity expansion strategies
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• Facility designs with expansion strategy: 92%
• Equipment swap: 25%• Fitting out: 58%• Drop block: 17%
• Capacity expansion: 100 - 400%
EquipmentSwap
Dro
p B
lock
Fitting Out
Phased expansion Initial capacity
Final capacity
#1 Equipment swap 2x 1000L 2x 2000L
#2 Equipment swap 2x 200L 2x 500L
#3 Fitting out 1x 2000L 2x 2000L
#4 Drop block 2x 2000L 4x 2000L
#5 Fitting out 2x 1000L 4x 1000L
#6 Fitting out 1x 500L 2x 1000L
#7 Fitting out 2x 2000L 6x 2000L
#8 Fitting out/Drop block 4x 2000L 12x 2000L
#9 Fitting out 2x 2000L 4x 2000L
#10 Fitting out 1x 500L 1x 1000L
#11 Equipment swap 8x 500L 8x 2000L
#12 14x 2000L 14x 2000L
Flexible technology integration
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Facility design Perfusion F&F ADC
#1 Launch X
#2 Pilot
#3 Launch
#4 Commercial X
#5 Pilot X
#6 Launch X
#7 Commercial X
#8 Commercial
#9 Commercial X X X
#10 Launch X
#11 Commercial X X
#12 Commercial X
• 83% include a flexible fed-batch facility design:
• Fed-batch to perfusion: 42%• End-to-end manufacturing (API+F&F): 50%• Antibody Drug Conjugate (ADC): 8%
Summary
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• Single-use technology is to key enabler for flexibility
• Hybrid solutions prevalent in the facility designs for commercial production
• “Traditional” layout for upstream and downstream – ballroom design not embraced yet
• Expansion strategy considered in facility designs
• Design for implementation of new technologies
For more information
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Frank NygaardSenior Technology PartnerT: +45 3079 [email protected] with Frank Nygaard on LinkedIn
Blog by Frank Nygaard: Where does flexibility really matter?: http://www.nnepharmaplan.com/insights/on-the-move/where-does-flexibility-really-matter/
www.nnepharmaplan.com