This document discusses the medical applications of fermentation technology. It begins with an introduction to fermentation and how microorganisms can be used to produce useful chemicals. It then discusses the types and stages of industrial fermentation processes. Some key applications of fermentation in medicine discussed include the production of insulin, vaccines, interferons, vitamin B12, enzymes, and antibiotics. Modern fermentation allows for mass production of these substances using genetically engineered microorganisms.

1. Medical application of
fermentation technology
Done By :
Saifullah Khalid Al-Bedri

2. Out come
 Introduction
 Industrial Fermentation
 Types of fermentation
 Stages of Fermentation
 How is Fermentation used in Medicine Today

3. Introduction
 In the eyes of human beings, microorganisms are disease causing
organisms. However, factually, only a small fraction of the total microbial
populations are associated with disease production, and the remaining is
harmless or beneficial to human beings.
 These tiny organisms, with sizes ranging from less than a micrometer to a
few micrometer, are sometimes called small chemical factories because of
their ability to produce a variety of chemical substances that are useful for
us like ; wine, bread, cheese, beer, chocolate, coffee and yogurt.

4. What is fermentation ?
 Fermentation, a process traditionally known for the anaerobic conversion of
sugar to carbon dioxide and alcohol by yeast, now refers to an industrial
process of manufacturing a wide variety of metabolites and biomaterials
by using microorganisms or mammalian cells in a controlled culture
environment.
 Fermentation technology remains at the heart of rapidly growing
biopharmaceutical industry today, which is expected to expand even
more in the days ahead, in parallel with the progress in novel, targeted
drug discovery.

5. Industrial Fermentation
 Industrial fermentation is built on traditional principles but incorporates most
recent advancements of biotechnology and engineering in order to
maximize yield at a reduced cost.
 Critical factors include the choice of the organisms, the medium used to
grow the organism and the final products.
 In addition, the type and size of the bioreactor in which the fermentation
process is operated are also important factors.

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 Bioreactors are typically made of stainless steel vessels, but other types,
such as those that combine glass and stainless steel structures are also
available, and their media holding capacity might vary from few hundred
liters to tens of thousands of liters.
 The bioreactors must be able to maintain
1. high cell concentrations for high product yield.
2. culture environment with proper temperature, pH, dissolved oxygen, redox
potential and the concentration of nutrients.
3. sterile conditions
4. agitation to ensure homogeneous distribution of heat, air, substrates, and
cells.

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 The attributes of bioreactors differ based on their types but in general they
are equipped with impellers to ensure aeration, pH detector and adjustor,
temperature sensor and controller, oxygen sensor, inlet to add medium and
inoculums, outlet to recover products, and a computerized system to
monitor all parameters and growth condition of the organisms.
 Stirred tank reactor, typically of cylindrical shape and equipped with
multiple impellers mounted on a shaft driven by a motor, is one of the most
common type of reactors used in fermentation industries.
 Industrial fermentation is carried out in bioreactors using three different
schemes: batch, continuous and fed-batch fermentations. The choice of
the scheme depends on the type of the organism, raw materials and the
product of interest.

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10. Stages of Fermentation
 Biotechnology companies use two terms to define the stages of the
production process: upstream processes and downstream processes.
 Upstream process involves growing microorganisms in the fermenter for
product formation.
 downstream process mainly involves product recovery and purification,
product concentration and preparing products for commercialization

11. In Colum
preparation
Cell culture in
seed bioreactor
Media
preparation &
sterilization
Cell culture in
production
bioreactor
Harvest
Clarification
Purification
concentration
Polishing
Formulation
storage
packaging
Upstream Fermentation Downstream

12. Types of fermentation
1. Batch types fermentation
2. Fed batch fermentation
3. Continuous fermentation
4. Solid state fermentation
5. Anaerobic Fermentation
6. Aerobic Fermentation

13. 1. Batch fermentation
 Batch fermentation is a discontinuous process and the fermenter has to be
cleaned after each process and a fresh batch started.
 It includes the following 5 steps:
1. Medium added
2. Fermenter sterilized
3. Inoculum added
4. Fermentation followed to completion
5. Culture harvested.

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Characteristics of a batch fermentation system
 Simplest fermenter operation
 Sterilization can be performed in the reactor
 All nutrients are added before inoculation
 Maximum levels of C and N are limited by inhibition of cell growth
 Biomass production limited by C/N load and production of toxic
waste products.

15. 2. FED BATCH FERMENTATION
 This fermentation is intermediate of both batch and continuous
fermentation.
 Sterile nutrients are added in increments .
Characters of fed batch fermentation
 Initial medium concentration is relatively low.
 Medium constituents are added continuously or in increments.
 Controlled feed results in higher biomass and product yields.
 Fermentation is still limited by accumulation of toxic end products.
 Finally the products are harvested in one stroke.

16. 3. CONTINUOUS FERMENTATION
 It is a continuous process where the nutrient is continuously added to the
fermented at a fixed rate.
 The organisms are continuously maintained at logarithmic stage.
 The products are recovered continuously
 The fomenters in this type are called “ flow through’’ fermentation.

17. Disadvantages of continuous
fermentation
1. Complete sterilization is difficult
2. More prone to contamination

18. 4. SOLID STATE FERMENTATION
 The growth of microorganisms on moist solid substrate particles in the
absence or mere absence of visible liquid water between the particles.
 The moisture content of solid substrate ranges between 12-80%.
 The water content of a typical sub mentation is more than 95%.
 SSF’s are usually used for the fermentation of agricultural products or foods,
such as rice, wheat, barley, corn and soybeans.
 Some food fermentations involving SSF: Wheat by Aspergillus Soybean by
Rhizopus Soybean by Aspergillus

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Phases of solid state fermentation
Gaseous
Phase
Liquid
Phase
Solid
Phase
An inert
solid
support
Natural
solid
materials

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Characteristics of solid state fermentation
1. The substrate may require preparation or pretreatment like, Chopping or
grinding-reduce particle size.
2. Microorganism is usually a filamentous fungus requiring aerobic condition.
3. The Inoculum is mixed into substrate to fermentation.
4. Cooking or chemical hydrolysis. Pasteurization or sterilization-reduce
contaminants.

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Advantage of SSF
1. A lower chance of contamination
due to low moisture levels.
2. Ease of product separation.
3. Energy efficiency.
4. Development of fully
differentiated structures.
Disadvantage
1. Heterogeneous nature of the
media, due to poor mixing
characteristics.
2. At high agitation speeds mycelial
cells may be damage.
3. Rotary-tray or rotating-drum
fermenters are often used.

22. 5. Anaerobic Fermentation
 In anaerobic fermentation, a provision for aeration is usually not needed.
 The air present in the headspace of the fermenter should be replaced by
CO2, H2, N2 or a suitable mixture of these.
 The fermentation usually liberates CO2 and H2
 Recovery of products from anaerobic fermenters does not require
anaerobic conditions. .

23. 6. Aerobic Fermentation
 The main feature of aerobic fermentation is the provision for adequate
aeration.
 In addition, these fermenters may have a mechanism for stirring and mixing
of the medium and cells.
 Aerobic fermenters may be either of the
(i) stirred tank type in which mechanical motor driven stirrers are provided
(ii) of air lift type in which no mechanical stirrers are used and the agitation
is achieved by the air bubbles generated by the air supply.

24. How is Fermentation used in Medicine Today:
1. In manufacture of insulin
2. In production of vaccines
3. In production of interferon
4. For the production of vitamin B12.
5. For the production of enzymes.
6. Recombinant Proteins.
7. Gene Therapy
8. Antimicrobial Drugs
9. Antibacterial
10.Antifungal
11.Antiviral
12.Antiparasitic Drugs
13.Antitumor Antibiotics
14. Steroids
15. Hypocholesterolemia Agents
16. Antihypertensive Agents
17. Alkaloids
18. Solvents
19. Intermediate Compounds
20. Monoclonal Antibodies
21. Bacillus Calmette–Guérin (BCG
22. Site Specific Immunotherapies
23. Probiotics
24. Diagnostic Products
25. Biopolymers
26. Perspectives

25. 1. For the production of insulin:
 The people who are diabetic especially the Type-I nature, require daily
administration of insulin. Previously the insulin necessary was obtained
from animals like pigs and buffalo for the purpose.
 But due to growth in population and also the disease incidence, the
demand for insulin has become several folds. So to maintain a steady
supply of insulin to the market, fermentation technology is used. Here, E-
coli bacteria which of genetically modified to produce human insulin is
employed. This bacteria has a small life cycle of only a few minutes to grow
and multiply. So copious amounts of insulin are produced by fermentation.
The two amino acid strands of insulin are obtained separately which are
sealed to produce insulin.

26. 2. Vaccines:
 Vaccines are prophylactic substances used to prevent infections. There are
different types of vaccines like living, dead and also genetically
engineered vaccines.
 rRDNA technology produces the genetically engineered vaccines like
hepatitis-B by employing fermentation process.

27. 3. Interferons:
 These are the substances which are used as antiviral drugs.
Fermentation tanks in industry
 They are substances which prevent the virus from binding to the host cell
and also growing inside it.

28. 4. Production of vitamin B12:
 Vitamin B12 is a very complex and bulky molecule. It would be
complicated and time-consuming to synthesize it in step by step manner by
chemical processes. However, it can be readily manufactured in a short
time by fermentation technology.
 Also, the product is pure without any contamination. It is widely used for the
treatment of anemia.

29. 5. Industrial enzymes:
 Fermentation produces enzymes needed for the industrial application, i.e.,
in large scale.
 Examples are
1. Protease an enzymes used for medical treatments of inflammation are
produced from fungus Aspergillus niger.
2. Enzymes amylases which are used to enhance digestion.

30. References
 Rahman, M. (2013). Medical applications of fermentation technology.
Advanced Materials Research, Trans Tech Publ.

31. Thanks for your attentions
Any Question ?