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Industrial Microbiology INDM 4005 Lecture 2 10/02/04

Industrial Microbiology INDM 4005 Lecture 2 10/02/04. Management Of Microbial Processes / Quality Assurance. Overview:  Principles of GMP  Process design / optimisation  Economics. Fermentation Economics. OBJECTIVE - yield a product at a competitive price BASIC OBJECTIVES.

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Industrial Microbiology INDM 4005 Lecture 2 10/02/04

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  1. Industrial MicrobiologyINDM 4005Lecture 210/02/04

  2. Management Of Microbial Processes / Quality Assurance Overview:  Principles of GMP  Process design / optimisation  Economics

  3. Fermentation Economics OBJECTIVE - yield a product at a competitive price BASIC OBJECTIVES.  Capital investment a minimum  Inexpensive raw materials  High yielding strain of microorganism  Labour saving and automation  Batch Production cycles as short as possible  Recovery and purification - simple & rapid  Minimise waste streams  Heat and power used efficiently  Space requirement minimised

  4. Major Areas of Cost Minimisation 1. Isolation and handling of microorganism 2. Plant and equipment 3. Media 4. Air sterilisation 5. Heating and cooling 6. Aeration and agitation 7. Recovery cost 8. Process time and duration 9. Prevention of contamination See Stanbury and Whitaker p.231

  5. Fermentation Economics • With so many criteria to consider a compromise is often reached for individual processes • It is important to know the cost breakdown • (Nyiri and Charles, 1977) concluded there are 4 main components contributing to process cost - Raw material - Fixed costs - Utilities - Labour • (Atkinson & Mavituna, 1991) report use of cost indices to update historical figures

  6. Fermentation Economics • Government intervention is often required to make fermentation processes economically viable • Acetone-butanol and penicillin during 2nd world war • Agricultural aid programmes in the US made available low-cost supplies of grain to promote fermentation based industry • Changes in EC policy encouraged fermentation companies to buy sugar and starch at reduced prices to compete on a worldwide scale • Reference: Small bugs, big business: The economic power of the microbe, Arnold L. Demain: Biotechnology advances 18 (2000) 499-514

  7. Isolation and handling of microorganism • Can the microorganism grow on simple cheap media? • Can it grow at higher temperatures? • Does it have better resistance to contamination? • Strain improvement, 1% increase in product output could pay for a mutation programme

  8. Plant and equipment • Relationship exist between cost and size of an item of equipment cost1 size1 cost2 size 2 n=scale factor Brewing 0.6, SCP, 0.7 to 0.8 Antibody production 0.6 Fermentation production 0.75 n =

  9. Media • Media can represent up to 73% of the total production cost in a fermentation process • The organic carbon source is usually the most expensive component • In a cost study analysis for tissue plasminogen activator by a mammalian -cell process, fermentation materials accounted for 75% of the total raw materials cost • A variety of waste material has commonly been used but they have restrictions variability impurities high water content seasonal variations

  10. Air Sterilisation • Production of large volumes of sterile air for aerobic fermentations is costly • Using sterilisation by heat is too expensive • Commonplace to use fixed pore membrane filters • Contamination probability of 1 in 1000 is acceptable economically, (Banks, 1979)

  11. Heating and Cooling • Heating and cooling should be avoided in fermentation processes • However this is virtually impossible to achieve • Good process design should minimize heating and cooling steps • Heating required for sterilisation or product concentration • Cooling equipment can represent 10-15% of the investment costs for SCP production (Moo-Young, 1977)

  12. Aeration and Agitation • Virtually all fermentation processes require some form of mixing • In processes that have a high oxygen demand eg antibiotics, acetic acid production, aeration is considered a major economic consideration • A 6-day antibiotic fermentation in a 100m3 fermenter uses approx $8,000 of power • Hydrocarbon based feedstocks in yeast fermentation require 3 times as much oxygen as carbohydrate substrates which has cost implications

  13. Recovery Costs • Older fermentations had a cost split of 1:1 between fermentation costs and isolation/purification costs (Reisman, 1993) • With advent of rDNA technology split now 1:8 or 1:10 • Capital investment on downstream processing equipment is expensive • Extraction / purification procedures need to be validated by FDA, thereby incurring higher cost

  14. Calculation of productivity, cost, profit, optimum production cycle. PRODUCTIVITY In a batch process productivity must be calculated for the complete cycle. The total time (t) for a fermentation may be calculated; t = 1/m (ln [Xf/Xo] ) + tT + tL + tD where m = maximum specific growth rate Xo = initial cell conc. Xf = final cell conc. tT = turn-around time (washing, filling, sterilisation, etc) tD = delay time until inoculation tL= lag time after inoculation

  15. Productivity The overall productivity P is given byP = Xf/ t It will be possible from this equation to determine the effect of process changes on the overall productivity. For example, a larger initial inoculum would increase Xo and shorten the process time. Actively growing inocula would reduce the lag time (tL)

  16. Effect of running time on productivity and cost - optimum time of harvesting In Stanbury and Whitaker

  17. Batch-Process Cycle Time • In a batch process productivity must be determined for a complete process cycle • Productivity is defined as units of product generated per unit of fermenter volume in a given time I.e, grams of product per litre per hour • In fermentations with short growth cycles 14-24 (Bakers yeast) hours the turnaround time is more important that for long fermentations 6-7 days (penicillin) in terms of productivity

  18. Continuous Culture • Few large scale continuous-culture processes are in operation, microbial biomass, glucose isomerase, yoghurt, (Heijnen, 1992) • Nonetheless it is possible to compare batch v continuous culture productivity • Basically the faster the organism grows (maximum specific growth rate) the more favourable continuous over batch (Wang et al., 1979) • However disadvantages outweigh the advantages • Manufacturers reluctant to make radical changes to established and validated processes

  19. Hazard Analysis Critical Control Point(HACCP) • Introduction • Beer safety and HACCP • The basics of HACCP • HACCP Terminology and Definitions • Steps to develop a HACCP Plan • Apply 7 principles • HACCP and SOPs • Explanation of a typical critical control point in Microbreweries • General flow diagram of a brewing process • CCP Decision Tree

  20. Conclusion • Understand the importance of being able to manage microbial processes • What is HACCP? • How to implement HACCP • Fermentation economics • How to calculate productivity in batch culture

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