The document summarizes data from 12 biopharmaceutical flexible facility projects. Common elements included the use of single-use bioreactors and technology to increase flexibility. Most facilities used campaign manufacturing. Expansion strategies included equipment swapping, fitting out unused space, and installing additional single-use bioreactors. The majority of facilities were designed to enable implementation of new technologies like perfusion and antibody drug conjugates.
2. 2
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
3. The 12 projects
Common denominators
3
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
4. The 12 projects
The dataset
4
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
5. Process design
5
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 designs
2) Concurrent: Manufacturing of different products in cell culture possible at the same time
6. Facility design and manufacturing strategy
Campaign 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
6
Downstream DownstreamUpstream
Downstream
(1 week)
Cell culture
(3 weeks)
DownstreamUpstream Upstream
7. Facility design
7
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)
8. Single-use implementation
8
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
11. Flexible technology integration
11
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%
12. Summary
12
• 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
13. For more information
13
Frank Nygaard
Senior Technology Partner
T: +45 3079 9785
fkny@nnepharmaplan.com
Connect 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