Bioprocessing

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Bioprocessing

• PHSC 438
• October 2006
• Dr. Tim Bloom

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Overview

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

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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

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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

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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

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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

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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

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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

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Culture Scale Affects
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Microbial Products

• Small molecules
• Vitamins
• Amino acids
• Antibiotics
• Alcohols
• Organic solvents
• Proteins
• Therapeutic proteins
• Reagent enzymes

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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

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Labor Intensive Viral Production
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Mammalian Cell Products

• Proteins
• Antibodies
• Cytokines
• Growth factors
• Viral vaccines
• Also more economicalif grown in tanks

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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

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Process Development Overview

• Engineer cells to make product
• Optimize growth conditions
• Develop purification protocols
• Establish formulation

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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

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Growth Requires

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

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Cell Culture Growth Curve
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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)

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Formulation

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

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From the Beginning

• Cells can be grown as individuals
• Bacteria and yeast
• Animal cells
• Plant cells
• How?

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Next Time

• Kinds of cells used in industry
• Requirements for industrial scale cell growth
• Systems used to keep cells happy