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Lauren O’Brien, Adrienne Campbell, Lewis Reis, Paul Stewart

Production Bioreactor – PBR1. Lauren O’Brien, Adrienne Campbell, Lewis Reis, Paul Stewart. Outline. Bioreactor Operation Main Factors Affecting Bioreactor Productivity Optimization Final Design Cost and Suppliers Alternative Reactors Question Period . Bioreactor OPERATION .

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Lauren O’Brien, Adrienne Campbell, Lewis Reis, Paul Stewart

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  1. Production Bioreactor – PBR1 Lauren O’Brien, Adrienne Campbell, Lewis Reis, Paul Stewart

  2. Outline Bioreactor Operation Main Factors Affecting Bioreactor Productivity Optimization Final Design Cost and Suppliers Alternative Reactors Question Period

  3. Bioreactor OPERATION Purpose: Growth of the hybridoma culture and production of monoclonal antibodies. Bioreactor volume: 18981 L Mab Production: 30.26 kg/batch

  4. Main factors affecting bioreactor productivity • fermentation temperature • dissolved oxygen content • supplied nutrient • waste product accumulation

  5. Optimization Effect of Air Flow Rate on mAb Production Initial Air Flow Rate: 1187 kg/hr

  6. Optimization Effect of Mass Flow Rate of Stream S-108 on Bioreactor Volume and mAb Production Initial Flow Rate of S-108: 10112 kg/hr Initial Medium Percentage: 1.8

  7. Optimization Effect of Mass Flow Rate of Stream S-109 on Reactor Volume and mAb Production Initial Flow Rate of S-109: 1077 kg/hr Initial Medium Percentage: 15.7

  8. Final Design

  9. Cost and suppliers

  10. Alternative reactors • In Vivo • Inject the hydridoma cells into the peritoneal cavity of a mouse. • Hybridoma cells multiply and produce fluid (ascites) in its abdomen. • The mice are then ‘tapped’ and the mAb rich fluid is removed • Advantages • Inexpensive, easy to use, familiar • Usually produces very high mAb concentrations that often do not require further concentration procedures that can denature antibody and decrease effectiveness. • Disadvantages • Contaminating mouse proteins • Can cause pain or distress • Animal welfare issues

  11. Alternative reactors • Semi-Permeable Membrane Based Systems • Hollow Fiber Membrane System • Cells are maintained in a compartment separated from the media reservoir by a selective membrane. Cells are perfused continuously with media, but are not exposed to shear. • Advantages • More effective for supplying nutrients and removing waste • High-density cultures, and therefore higher monoclonal antibody concentrations compared to batch • Disadvantages • More complicated and expensive • High-density culture methods require frequent monitoring

  12. Question Period

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