1. Introduction on Scale Up Fine Chemicals : From Lab to Plant Site By Wiratni, PhD Gadjah Mada University Yogyakarta - Indonesia

2. Evolution of chemical engineering Global trend in chemical industries Mass productionSpecialties/fine chemicals Focused on CONVERSIONEmphasized on PROPERTIES ‘Conventional’ Chemical Engineering New view in chemical engineering: Product Engineering

3. Chemical industries in developing countries DESIGNERS PROCESS ENGINEERS LICENCES OPERATIONS NET PROFIT

4. Flexibility for changes International chemical giants (DuPont, BASF, Dow) Chemical plants in developing countries Natural resources Commoditization Specialties LICENSE! STRONG R & D

5. Raw materials Crude products Fine chemicals Price scale Chemical engineering Product engineering

6. Position of Biotechnology Highly specific in producing particular compounds  important role in fine chemical production Highly specific in producing particular compounds  important role in fine chemical production Characteristics: Characteristics: - higher level of uncertainty - decreasing performance of microorganisms

7. Bioprocess Engineering BIOREACTOR Raw material (substrate) Microorganism/enzyme PURIFICATION UNITS Fermentation Broth Product WASTE DOWNSTREAM PROCESSING

8. Downstream processing Very costly; can take up to 70% of total investment Very costly; can take up to 70% of total investment Very important in bioprocess as it determines the specification of product (purity, physical/chemical characteristics, etc.) Very important in bioprocess as it determines the specification of product (purity, physical/chemical characteristics, etc.)

9. Example of Bioproduct Poly-  -Hydroxy-Butirate (PHB): Biodegradable polymer with high biocompatibility for medical purposes Biodegradable polymer with high biocompatibility for medical purposes Produced intracellularly by microorganisms (e.g. Alcaligenes euthrophus), using sugar compounds as substrate Produced intracellularly by microorganisms (e.g. Alcaligenes euthrophus), using sugar compounds as substrate

10. Nature of PHB Characteristics: Amount of PHB accumulated Amount of PHB accumulated Degree of crystallinity Degree of crystallinity Physical/mechanical properties Physical/mechanical properties Purity Purity VERY SENSITIVE TO PROCESS CONDITIONS

11. Problems PHB is carbon storage for the microorganisms: they will accumulate it when they have plenty of food, and will consume it when they are lack of food PHB is carbon storage for the microorganisms: they will accumulate it when they have plenty of food, and will consume it when they are lack of food Must determine: Must determine: When is the optimum harvesting time??

12. Problems PHB is biodegradable, and so it is susceptible to oxidation, chlorination, etc. that may lead to decreasing molecular weight. PHB is biodegradable, and so it is susceptible to oxidation, chlorination, etc. that may lead to decreasing molecular weight. Must determine: Must determine: What chemicals to be used in purification process? What temperature does not destructive to PHB?

13. Problems If the previous questions have been answered through laboratory experiments, you may define optimum conditions (composition of substrate, temperature, pH, etc) for PHB production. If the previous questions have been answered through laboratory experiments, you may define optimum conditions (composition of substrate, temperature, pH, etc) for PHB production. Bigger problem: Bigger problem: Do those optimum conditions for Erlenmeyer flask still hold for 100 L fermentor?

14. Menghitung kebutuhan power Power number Reynold number

15. Example: Making homogeneous solutions LAB SCALE COMMERCIAL SCALE (IDEAL) (NON-IDEAL)

16. Why studying scale-up techniques?

17. Producing Fine Chemicals The technology is not matured yet The technology is not matured yet Very specific for each particular product Very specific for each particular product Very costly if buy licensed technology for each product Very costly if buy licensed technology for each product Companies must have very strong R&D with two fold tasks: Companies must have very strong R&D with two fold tasks: 1. developing new products 2. designing commercial units (SCALE- UP)

18. Scale Up in Essential Oil Production Laboratory experiment Pilot scaleCommercial scale SCALE UP PROCESS

19. Route to Commercialization LABORATORY SCALE MATHEMATICAL MODELS TRIAL AND ERROR VERIFICATION IN PILOT PLANT COMMERCIAL PRODUCTION ERRORS