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Introduction to Bioprocess 12th. July 2010 CEPP, UTM Skudai, Johor Prof. Dr. Hesham A. El Enshasy Faculty of Chemical Engineering CEPP, UTM, Skudai, Malaysia
The oldest Known Biotech. Protocol for Yeast production  Bread and Beer Manufacturing Process, the 5th. Dynastry (ca 2400 BC) Leiden Egyptian Museum, Holland
Milestones of Bioprocess Industry Development
Solvents   Organic acids  Pre 1940s Baker’s yeast  Amino acids  Antibiotics  Enzymes Probiotics  Industrial Bioprocessing Vaccine biopolymers Pre 1980s Biosurfactants SCP rProteins  MAb Biopharmaceuticals  Post 1980s Plant Bioactive compounds  BioDiesel  X
Some of Major Industrial Fermentation Products  Ref. Bioprocessing-from Biotechnology to Biorefinery (S.T. Yang, Ed.), Elsevier Press, 2007.
Stages of Industrial Biotechnology from 1900 to date
Industrial Bioprocessing: Microbial cells Bioprocess Development
Determination of process bottleneck(s) Bioprocess Optimization in Lab. scale (Development of cultivation strategy to reach the maximal productivity) Scaling up of the Process Down Stream  (Separation/Isolation/Purification and increase of product Stability)
Substrate Input and Output Oxygen Carbon dioxide  Carbon and Energy  Sources   Biomass CELL Metabolite(s) Nitrogen Source Water  Other requirements (P, S,Na,K,Mg,etc…) Heat
General Requirements for Medium Composition It will Produce the maximal yield of product(s) or biomass per gram of substrate used (High Yield Coefficient)  It will produce the maximal concentration of product or biomass (High volumetric production)  It will permit the maximal yield of product formation  (Maximal productivity) There will be the minimal yield of undesirable products It will be of consistent quality and be readily available throughout the year It will cause minimal problems during media preparation and sterilization  It will cause minimal problems in other aspects of the production process particularly Aeration and agitation, extraction and waste treatment
Cultivation Media
Overviews on the elemental composition of the microorganisms
From Petri-dish to Bioreactor Primary Scaling up
What can we use Petri dish for Strain Isolation and Identification work As first step for inoculum propagation  Sterility testing Rapid screening for certain microbial metabolites  Antimicrobial sensitivity testing Short term strain preservation
What can we use Shake flask for Primary production of certain metabolites  Genetic material preparation (cell mass production for DNA isolation) Medium optimization (C-, N-, P- and elements-sources and concentrations)       Cultivation conditions optimization (Temperature, pH) Primary understanding of oxygen and mixing requirements through the change in  (Shaking intensity,  Shaking eccentricity, working volume and polymer addition) Primary data for Growth and product formation kinetics
Bio-Factories in Industrial Biotechnology Mammalian cells Insect cells Invertebrate cells Plant cell Algae Fungi Actinomycetes Bacteria
Plant: the oldest Natural source of metabolites
New Process for Plant Metabolites Production
Why Plant Cell Bioreactor ?  It is independent of geographical and seasonal variations and various environmental factors.  It offers a defined production system, which ensure continuous supply of products, uniform quality and yield It is possible to produce novel compounds that are not normally found in parent plant.  It is independent of political interface Efficient downstream recovery with low cost and minimum number of steps. High efficient production rate with significant short production time Fully Compliance to cGMP requirements for Biopharmaceuticals
PhotoBioreactor - Plant cells - Algal cells
Mammalian cells Tissue Engineering Cell Culture
Different levels for mammalian cells / insect cells  cultivation Scaling up
Different levels of cells cultivation Small scale (T-flask, 24 well) Non-Optimized Cell Productivity Shear Stress Spinner flask Rolling bottles Semi-Optimized Mixing Bioreactor Level (STR, Air-Lift, Hollow fiber) Fully-Optimized
BioFuel: The source of clean energy
Bioreactor: The heart of Industrial Bioprocessing Facility Since mid-1950s no major Change in STR Engineering Change mainly in: ,[object Object]
 Valves
 Material Finish
 Sensors (on-line, in-line and off-line) ,[object Object],[object Object]
 Bioprocess control All software and control/recording system must be cGMP approved and validated
Manufacturing Cost in Bioprocess Industries

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Lecture 2 introduction to bioprocess

  • 1. Introduction to Bioprocess 12th. July 2010 CEPP, UTM Skudai, Johor Prof. Dr. Hesham A. El Enshasy Faculty of Chemical Engineering CEPP, UTM, Skudai, Malaysia
  • 2. The oldest Known Biotech. Protocol for Yeast production Bread and Beer Manufacturing Process, the 5th. Dynastry (ca 2400 BC) Leiden Egyptian Museum, Holland
  • 3. Milestones of Bioprocess Industry Development
  • 4. Solvents Organic acids Pre 1940s Baker’s yeast Amino acids Antibiotics Enzymes Probiotics Industrial Bioprocessing Vaccine biopolymers Pre 1980s Biosurfactants SCP rProteins MAb Biopharmaceuticals Post 1980s Plant Bioactive compounds BioDiesel X
  • 5. Some of Major Industrial Fermentation Products Ref. Bioprocessing-from Biotechnology to Biorefinery (S.T. Yang, Ed.), Elsevier Press, 2007.
  • 6. Stages of Industrial Biotechnology from 1900 to date
  • 7. Industrial Bioprocessing: Microbial cells Bioprocess Development
  • 8. Determination of process bottleneck(s) Bioprocess Optimization in Lab. scale (Development of cultivation strategy to reach the maximal productivity) Scaling up of the Process Down Stream (Separation/Isolation/Purification and increase of product Stability)
  • 9. Substrate Input and Output Oxygen Carbon dioxide Carbon and Energy Sources Biomass CELL Metabolite(s) Nitrogen Source Water Other requirements (P, S,Na,K,Mg,etc…) Heat
  • 10. General Requirements for Medium Composition It will Produce the maximal yield of product(s) or biomass per gram of substrate used (High Yield Coefficient) It will produce the maximal concentration of product or biomass (High volumetric production) It will permit the maximal yield of product formation (Maximal productivity) There will be the minimal yield of undesirable products It will be of consistent quality and be readily available throughout the year It will cause minimal problems during media preparation and sterilization It will cause minimal problems in other aspects of the production process particularly Aeration and agitation, extraction and waste treatment
  • 12. Overviews on the elemental composition of the microorganisms
  • 13. From Petri-dish to Bioreactor Primary Scaling up
  • 14. What can we use Petri dish for Strain Isolation and Identification work As first step for inoculum propagation Sterility testing Rapid screening for certain microbial metabolites Antimicrobial sensitivity testing Short term strain preservation
  • 15. What can we use Shake flask for Primary production of certain metabolites Genetic material preparation (cell mass production for DNA isolation) Medium optimization (C-, N-, P- and elements-sources and concentrations) Cultivation conditions optimization (Temperature, pH) Primary understanding of oxygen and mixing requirements through the change in (Shaking intensity, Shaking eccentricity, working volume and polymer addition) Primary data for Growth and product formation kinetics
  • 16.
  • 17. Bio-Factories in Industrial Biotechnology Mammalian cells Insect cells Invertebrate cells Plant cell Algae Fungi Actinomycetes Bacteria
  • 18. Plant: the oldest Natural source of metabolites
  • 19. New Process for Plant Metabolites Production
  • 20. Why Plant Cell Bioreactor ? It is independent of geographical and seasonal variations and various environmental factors. It offers a defined production system, which ensure continuous supply of products, uniform quality and yield It is possible to produce novel compounds that are not normally found in parent plant. It is independent of political interface Efficient downstream recovery with low cost and minimum number of steps. High efficient production rate with significant short production time Fully Compliance to cGMP requirements for Biopharmaceuticals
  • 21. PhotoBioreactor - Plant cells - Algal cells
  • 22. Mammalian cells Tissue Engineering Cell Culture
  • 23. Different levels for mammalian cells / insect cells cultivation Scaling up
  • 24. Different levels of cells cultivation Small scale (T-flask, 24 well) Non-Optimized Cell Productivity Shear Stress Spinner flask Rolling bottles Semi-Optimized Mixing Bioreactor Level (STR, Air-Lift, Hollow fiber) Fully-Optimized
  • 25. BioFuel: The source of clean energy
  • 26.
  • 29.
  • 30. Bioprocess control All software and control/recording system must be cGMP approved and validated
  • 31. Manufacturing Cost in Bioprocess Industries