Industrial Microbiology INDM 4005 Lecture 2 100204

1
Industrial MicrobiologyINDM 4005Lecture
210/02/04
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Management Of Microbial Processes / Quality
Assurance

• Overview
• ? Principles of GMP
• ? Process design / optimisation
• ? Economics

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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

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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

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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

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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

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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

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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

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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

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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)

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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)

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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

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Recovery Costs

• Older fermentations had a cost split of 11
  between fermentation costs and isolation/purificat
  ion costs (Reisman, 1993)
• With advent of rDNA technology split now 18 or
  110
• Capital investment on downstream processing
  equipment is expensive
• Extraction / purification procedures need to be
  validated by FDA, thereby incurring higher cost

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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

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Productivity

• The overall productivity P is given by P 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)

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

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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

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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

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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