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Bioprocessing

Bioprocessing. PHSC 438 October 2006 Dr. Tim Bloom. Overview. History Product examples Using microbial cells Using mammalian cells Preview of the rest of the semester. Biotechnology. Using biological systems for production Using living cells/organisms Using cellular components

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Bioprocessing

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  1. Bioprocessing PHSC 438 October 2006 Dr. Tim Bloom

  2. Overview • History • Product examples • Using microbial cells • Using mammalian cells • Preview of the rest of the semester

  3. Biotechnology • Using biological systems for production • Using living cells/organisms • Using cellular components • Convert raw materials into product • Does not include agriculture/ranching • Unless organism is genetically modified • Golden rice • Growth-enhanced salmon

  4. Bioprocessing • Branch of biotechnology • Using genetically engineered organisms • Contain foreign DNA • Usually codes a protein used as a product • Insulin • Human growth hormone • Microbial cells, mammalian cells, plants, intact animals

  5. History of Biotech • First products not commercial • Beer, wine, vinegar • Bread and cheese • Micro-organisms convert raw materials into more useful product • Empirical development with local microbes

  6. More Recent • Use enzymes to economize production • Proteases for leather • Amylases for simple sugars • Industrial scale enzyme production • Required reliable sources of enzymes • Cheap source is microbes • Growth and harvest techniques developed

  7. Industrial Use of Enzymes • Enzyme trapped in a column • Raw materials passed through • Products formed by interaction with trapped enzyme • Product captured in eluant from column

  8. The Golden Age • After World War II • Development of antibiotics • Produced by bacteria and fungi • Development of larger scale techniques • Tanks for growing cells • Systems for moving sterile liquids around • Systems for harvesting products from cells

  9. Culture Scale Affects…

  10. Microbial Products • Small molecules • Vitamins • Amino acids • Antibiotics • Alcohols • Organic solvents • Proteins • Therapeutic proteins • Reagent enzymes

  11. Non-microbial Cells • Need for vaccines against viruses • Started with chicken eggs • Moved to cultured monkey cells • Developed systems for large-scale growth • More difficult than growing microbes • Continued development for economy of scale

  12. Labor Intensive Viral Production

  13. Mammalian Cell Products • Proteins • Antibodies • Cytokines • Growth factors • Viral vaccines • Also more economicalif grown in tanks

  14. Moving Forward • Current efforts focused on improvement • Developing new products • Creating useful new cell hosts • Optimizing efficient growth and harvest of cells • Improving purification technology • More convenient formulations for administration

  15. Process Development Overview • Engineer cells to make product • Optimize growth conditions • Develop purification protocols • Establish formulation

  16. Engineering Cells • Insert foreign DNA into host • Codes for protein (product) • Codes for enzyme (makes product) • Codes for regulator (changes product level) • Bottom line: cell host makes more of a product that unmodified cell can

  17. Growth Requires… • Nutrients • Dissolved oxygen • Waste removal (or dilution) • Appropriate pH and temperature • Supplied by medium • Controlled by (semi-) automated systems

  18. Cell Culture Growth Curve

  19. Product Purification • Separation from other things in system • Host cells • Host cell components • Media components undesired in final product • Based on chemical/physical properties • Interactions with other molecules (chromatography) • Size (filtration) • Solubility (precipitation)

  20. Formulation • Excipients • Dosage form/administration route • Protect product • Physical degradation • Chemical degradation

  21. From the Beginning… • Cells can be grown as individuals • Bacteria and yeast • Animal cells • Plant cells • How?

  22. Next Time… • Kinds of cells used in industry • Requirements for industrial scale cell growth • Systems used to keep cells happy

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