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

11. Cultivation Media

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

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

27. Valves

28. Material Finish

30. Bioprocess control All software and control/recording system must be cGMP approved and validated

31. Manufacturing Cost in Bioprocess Industries

32. BioFuture of Industrial Bioprocess

33. Thank You