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Introduction to Bioprocess12th. July 2010CEPP, UTM Skudai, JohorProf. Dr. Hesham A. El EnshasyFaculty of Chemical EngineeringCEPP, 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 1940sBaker’s yeast Amino acids Antibiotics EnzymesProbiotics Industrial BioprocessingVaccinebiopolymersPre 1980sBiosurfactantsSCPrProteins MAbBiopharmaceuticals Post 1980sPlant Bioactivecompounds 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 cellsBioprocess Development
Determination of process bottleneck(s)Bioprocess Optimization in Lab. scale(Development of cultivation strategy to reach the maximal productivity)Scaling up of the ProcessDown Stream (Separation/Isolation/Purification and increase of product Stability)
Substrate Input and OutputOxygenCarbon dioxide Carbon and Energy Sources  BiomassCELLMetabolite(s)Nitrogen SourceWater Other requirements(P, S,Na,K,Mg,etc…)Heat
General Requirements for Medium CompositionIt 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 productsIt will be of consistent quality and be readily available throughout the yearIt will cause minimal problems during media preparation and sterilization It will cause minimal problems in other aspects of the production process particularlyAeration and agitation, extraction and waste treatment
Cultivation Media
Overviews on the elemental composition of the microorganisms
From Petri-dish to BioreactorPrimary Scaling up
What can we use Petri dish forStrain Isolation and Identification workAs first step for inoculum propagation Sterility testingRapid screening for certain microbial metabolites Antimicrobial sensitivity testingShort term strain preservation
What can we use Shake flask forPrimary 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
Lecture 2 introduction to bioprocess
Bio-Factories in Industrial BiotechnologyMammalian cellsInsect cellsInvertebrate cellsPlant cellAlgaeFungiActinomycetesBacteria
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 yieldIt is possible to produce novel compounds that are not normally found in parent plant. It is independent of political interfaceEfficient downstream recovery with low cost and minimum number of steps.High efficient production rate with significant short production timeFully Compliance to cGMP requirements for Biopharmaceuticals
PhotoBioreactor- Plant cells- Algal cells
Mammalian cellsTissue EngineeringCell Culture
Different levels for mammalian cells / insect cells  cultivationScaling up
Different levels of cells cultivationSmall scale (T-flask, 24 well)Non-OptimizedCell ProductivityShear StressSpinner flaskRolling bottlesSemi-OptimizedMixingBioreactor Level(STR, Air-Lift, Hollow fiber)Fully-Optimized
BioFuel: The source of clean energy
Bioreactor: The heart of Industrial Bioprocessing FacilitySince mid-1950s no majorChange in STR EngineeringChange mainly in: Sampling system
 Valves
 Material Finish
 Sensors (on-line, in-line and off-line) Control systemExhaust gasAnalyzerFeed pump(s)pHTemperatureDOAerationPressurePower consumptionWeight / volumeStirrer SpeedMeasurement and open or closed loop controlMeasurement onlyCommon measurement and control of bioreactors as generally accepted as routine equipment
 Bioprocess controlAll 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 Bioprocess12th. July 2010CEPP, UTM Skudai, JohorProf. Dr. Hesham A. El EnshasyFaculty of Chemical EngineeringCEPP, 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 1940sBaker’s yeast Amino acids Antibiotics EnzymesProbiotics Industrial BioprocessingVaccinebiopolymersPre 1980sBiosurfactantsSCPrProteins MAbBiopharmaceuticals Post 1980sPlant Bioactivecompounds 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 cellsBioprocess 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 ProcessDown Stream (Separation/Isolation/Purification and increase of product Stability)
  • 9. Substrate Input and OutputOxygenCarbon dioxide Carbon and Energy Sources BiomassCELLMetabolite(s)Nitrogen SourceWater Other requirements(P, S,Na,K,Mg,etc…)Heat
  • 10. General Requirements for Medium CompositionIt 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 productsIt will be of consistent quality and be readily available throughout the yearIt will cause minimal problems during media preparation and sterilization It will cause minimal problems in other aspects of the production process particularlyAeration and agitation, extraction and waste treatment
  • 12. Overviews on the elemental composition of the microorganisms
  • 13. From Petri-dish to BioreactorPrimary Scaling up
  • 14. What can we use Petri dish forStrain Isolation and Identification workAs first step for inoculum propagation Sterility testingRapid screening for certain microbial metabolites Antimicrobial sensitivity testingShort term strain preservation
  • 15. What can we use Shake flask forPrimary 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
  • 17. Bio-Factories in Industrial BiotechnologyMammalian cellsInsect cellsInvertebrate cellsPlant cellAlgaeFungiActinomycetesBacteria
  • 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 yieldIt is possible to produce novel compounds that are not normally found in parent plant. It is independent of political interfaceEfficient downstream recovery with low cost and minimum number of steps.High efficient production rate with significant short production timeFully Compliance to cGMP requirements for Biopharmaceuticals
  • 23. Different levels for mammalian cells / insect cells cultivationScaling up
  • 24. Different levels of cells cultivationSmall scale (T-flask, 24 well)Non-OptimizedCell ProductivityShear StressSpinner flaskRolling bottlesSemi-OptimizedMixingBioreactor Level(STR, Air-Lift, Hollow fiber)Fully-Optimized
  • 25. BioFuel: The source of clean energy
  • 26. Bioreactor: The heart of Industrial Bioprocessing FacilitySince mid-1950s no majorChange in STR EngineeringChange mainly in: Sampling system
  • 29. Sensors (on-line, in-line and off-line) Control systemExhaust gasAnalyzerFeed pump(s)pHTemperatureDOAerationPressurePower consumptionWeight / volumeStirrer SpeedMeasurement and open or closed loop controlMeasurement onlyCommon measurement and control of bioreactors as generally accepted as routine equipment
  • 30. Bioprocess controlAll software and control/recording system must be cGMP approved and validated
  • 31. Manufacturing Cost in Bioprocess Industries