Monoclonal Antibody Production

1
Monoclonal Antibody Production
Investigating a Bag Bioreactor System
Angelica Bitton Alain Laplume Allison
Turner
2
Overview

1. Process Overview
2. Single-Use Bioreactors
3. Model Manipulation
4. Findings
5. Sizing Selection
6. Cost Analysis
7. Conclusions Recommendations

3
Process Overview

• Bag Bioreactor System (BBS-102)

4
Single-Use Bioreactors

• Used in inoculation stages or pilot-plant scale
  fermentation steps
• LDPE liner or bag housed by stainless steel unit
• Agitation achieved by rocking mechanism or
  magnetic stirrer
• Reduced cleaning sterilization requirements
• Reduced validation requirements
• Increased flexibility in design

AAA
5
Model Manipulation

• Initial Conditions
• Operating temperature 37C
• Holding time 120 minutes
• Broth feed 58.5 kg/batch
• Capacity 5 x 100 L bags
• Inoculation medium solution 175.4 kg/batch
• Final mAb yield 19.2 kg/batch
• Manipulated Parameters
• Temperature, holding time, broth feed
• Bag capacity
• Inoculation medium solution

6
Findings

• Capacity 2 x 100 L bags
• Inoculation medium solution 22.5 kg/batch
• Final mAb yield 19.0 kg/batch

AAA
7
Sizing Selection

• XDR Xcellerex Disposable series
• Conventional SS vessel with LDPE insert
• Magnetic stirring mechanism
• Sartorius BIOSTAT CultiBag RM line
• LDPE bags housed by SS skid
• Rocking stirring mechanism
• GE Healthcare Wave bag bioreactor systems
• SYSTEM200 2 x 100 L
• Operation under perfusion possible
• Rocking stirring mechanism

8
Costing

• No vendor quotes available
• According to GE Healthcare
• Capital cost 30 conventional SS bioreactor
• Operating costs 1/3 conventional SS bioreactor
• SuperPro 2008 estimated costs
• Calculated Costs
• Bag bioreactor housing system
• 165,000.00
• Capital equipment cost per batch
• 600.00 (300.00 per 100 L bag)
• Utilities
• Meaningful estimate not feasible
• First 3 years
• 202,800.00

AAA
9
Conclusions Recommendations

• Single-use technology significantly reduces cost,
  validation, and cleaning requirements
• Reduction of media solution allows specified mAb
  yield of 19.0 kg/batch to be met with only 2 bags
• GE Healthcare Wave SYSTEM200 bag bioreactor
  system will meet the specific needs of this
  process
• Future investigations should assess the effect of
  holding time on the cell density process yield

10
THANK YOU QUESTIONS?