Page 1
Students are already aware that living organisms especially
microbes and biological processes therein are used for
making various household products (curd/yoghurt, idli,
kinema, etc.) and industrial products (ethanol). We have
already learnt in the previous class that living organisms
are endowed with a variety of metabolic processes which
lead to the formation of chemical compounds, called
metabolites, that are broadly classi??ed into primary
and secondary metabolites. Primary metabolites are the
compounds produced directly out of primary metabolic
pathways associated with essential cellular functions such
as growth and development. On the contrary, secondary
metabolites are intermediates or indirect products,
elaborated by entirely different metabolic pathways called
secondary metabolic pathways. Secondary metabolites take
part in a variety of functions. For example, they are used in
defence for protection against pathogens, phytoplanktons
and herbivores, to improve tolerance to abiotic stresses;
as attractants for insects and animals for fertilisation,
seed dispersal in plants or to contribute in causing the
displeasure to the unwanted feeders.
10.1 Historical
Perspective
10.2 Instrumentation
in Bioprocessing:
Bioreactor and
Fermenter Design
10.3 Operational Stages
of Bioprocess
10.4 Bioprocessing and
Biomanufacturing
of Desired Product
Bioprocessing and
Biomanufacturing
10
Chapter
Chapter 10_Bioprocessing and Bio-manuf.indd 231 23-01-2025 11:27:46
Reprint 2025-26
Page 2
Students are already aware that living organisms especially
microbes and biological processes therein are used for
making various household products (curd/yoghurt, idli,
kinema, etc.) and industrial products (ethanol). We have
already learnt in the previous class that living organisms
are endowed with a variety of metabolic processes which
lead to the formation of chemical compounds, called
metabolites, that are broadly classi??ed into primary
and secondary metabolites. Primary metabolites are the
compounds produced directly out of primary metabolic
pathways associated with essential cellular functions such
as growth and development. On the contrary, secondary
metabolites are intermediates or indirect products,
elaborated by entirely different metabolic pathways called
secondary metabolic pathways. Secondary metabolites take
part in a variety of functions. For example, they are used in
defence for protection against pathogens, phytoplanktons
and herbivores, to improve tolerance to abiotic stresses;
as attractants for insects and animals for fertilisation,
seed dispersal in plants or to contribute in causing the
displeasure to the unwanted feeders.
10.1 Historical
Perspective
10.2 Instrumentation
in Bioprocessing:
Bioreactor and
Fermenter Design
10.3 Operational Stages
of Bioprocess
10.4 Bioprocessing and
Biomanufacturing
of Desired Product
Bioprocessing and
Biomanufacturing
10
Chapter
Chapter 10_Bioprocessing and Bio-manuf.indd 231 23-01-2025 11:27:46
Reprint 2025-26
Biotechnology XII 232
Nowadays, most of these secondary metabolites have
a variety of applications in the form of pharmaceuticals,
dyes, food additives, enzymes, vitamins, etc. In view of the
variety of applications, production of these compounds
(biochemicals) at commercial level requires their production
in bulk quantities, as quantities produced naturally are
not suf??cient. These compounds are usually produced at
commercial level in a puri??ed form through a series of steps
covered under bioprocessing. For large scale production,
where large volume (on an average 100–10,000 litres) of
culture can be processed, the development of bioreactors
was required.
10.1 Historical Pers Pective After the breakthrough discovery of Penicillin and its
role in killing bacteria by Alexander Fleming in 1928,
the signi??cance of products from biological systems was
well understood. Now, the challenge before the scienti??c/
research community was to enhance the production
of penicillin. Production in larger amount for its use in
treatment would obviously require a systematic process
using the culture of biological entity in question, i.e.,
Penicillium species. The need of involvement of microbial
physiologist and other life scientists and technologists
was identi??ed. This followed the identi??cation of a number
of products of living organisms and processes especially
from microbes for application in bioprocessing. Many
companies and government laboratories, assisted by
different universities and institutions came together to
take up this challenge and efforts were made to increase
the production of penicillin. All this paved a way for the
emergence of a new area of biological applications, which
is now known as bioprocessing. Thus, bioprocessing
involves biological or living systems or their components
(e.g., enzymes, chloroplasts, etc.) and chemical engineering
processes to obtain the desired products at commercial
level as depicted in Fig. 10.4.
At industrial or commercial stage, all bioprocesses are
carried out in vessels called fermenter or bioreactor. We
are also aware that after the advent of rDNA technology,
Chapter 10_Bioprocessing and Bio-manuf.indd 232 23-01-2025 11:27:47
Reprint 2025-26
Page 3
Students are already aware that living organisms especially
microbes and biological processes therein are used for
making various household products (curd/yoghurt, idli,
kinema, etc.) and industrial products (ethanol). We have
already learnt in the previous class that living organisms
are endowed with a variety of metabolic processes which
lead to the formation of chemical compounds, called
metabolites, that are broadly classi??ed into primary
and secondary metabolites. Primary metabolites are the
compounds produced directly out of primary metabolic
pathways associated with essential cellular functions such
as growth and development. On the contrary, secondary
metabolites are intermediates or indirect products,
elaborated by entirely different metabolic pathways called
secondary metabolic pathways. Secondary metabolites take
part in a variety of functions. For example, they are used in
defence for protection against pathogens, phytoplanktons
and herbivores, to improve tolerance to abiotic stresses;
as attractants for insects and animals for fertilisation,
seed dispersal in plants or to contribute in causing the
displeasure to the unwanted feeders.
10.1 Historical
Perspective
10.2 Instrumentation
in Bioprocessing:
Bioreactor and
Fermenter Design
10.3 Operational Stages
of Bioprocess
10.4 Bioprocessing and
Biomanufacturing
of Desired Product
Bioprocessing and
Biomanufacturing
10
Chapter
Chapter 10_Bioprocessing and Bio-manuf.indd 231 23-01-2025 11:27:46
Reprint 2025-26
Biotechnology XII 232
Nowadays, most of these secondary metabolites have
a variety of applications in the form of pharmaceuticals,
dyes, food additives, enzymes, vitamins, etc. In view of the
variety of applications, production of these compounds
(biochemicals) at commercial level requires their production
in bulk quantities, as quantities produced naturally are
not suf??cient. These compounds are usually produced at
commercial level in a puri??ed form through a series of steps
covered under bioprocessing. For large scale production,
where large volume (on an average 100–10,000 litres) of
culture can be processed, the development of bioreactors
was required.
10.1 Historical Pers Pective After the breakthrough discovery of Penicillin and its
role in killing bacteria by Alexander Fleming in 1928,
the signi??cance of products from biological systems was
well understood. Now, the challenge before the scienti??c/
research community was to enhance the production
of penicillin. Production in larger amount for its use in
treatment would obviously require a systematic process
using the culture of biological entity in question, i.e.,
Penicillium species. The need of involvement of microbial
physiologist and other life scientists and technologists
was identi??ed. This followed the identi??cation of a number
of products of living organisms and processes especially
from microbes for application in bioprocessing. Many
companies and government laboratories, assisted by
different universities and institutions came together to
take up this challenge and efforts were made to increase
the production of penicillin. All this paved a way for the
emergence of a new area of biological applications, which
is now known as bioprocessing. Thus, bioprocessing
involves biological or living systems or their components
(e.g., enzymes, chloroplasts, etc.) and chemical engineering
processes to obtain the desired products at commercial
level as depicted in Fig. 10.4.
At industrial or commercial stage, all bioprocesses are
carried out in vessels called fermenter or bioreactor. We
are also aware that after the advent of rDNA technology,
Chapter 10_Bioprocessing and Bio-manuf.indd 232 23-01-2025 11:27:47
Reprint 2025-26
Bioprocessing and Biomanufacturing
233
Box 1
Discovery of Penicillin
It was in 1928 when Alexander Fleming
at St. Mary’s Hospital in London, while
trying to isolate boils causing bacterium,
Staphylococcus aureus, found that one of the
Petridishes was contaminated inadvertently
with a foreign entity. Instead of discarding
the Petri plate for disinfection, Fleming made
an important observation in the unwashed
contaminated plate that no bacteria grew near the invading entity. The observation surprised
Fleming’s intellect and he soon realised that this chance observation may be a meaningful
arena of interest.
Later this antibacterial foreign entity was identi??ed as a common mould, the Penicillium
notatum, and the metabolite secreted has powerful antibacterial properties called penicillin.
Its full potential as an effective antibiotic was established by Ernest Chain and Howard
Florey. This antibiotic was extensively used to treat the American soldiers wounded in World
War II. Fleming, Chain and Florey were awarded the Nobel Prize in 1945 for this discovery.
microbes are extensively employed for the production of a
number of biological material for the welfare of mankind.
10.2 i nstrumentation in Bio Processing :
Bioreactor and Fermenter d esign Bioreactor is an engineered vessel made up of glass or
steel that supports a biologically active environment,
where cells can be cultivated under aseptic conditions with
appropriate nutritional and environmental requirements.
In a bioreactor, the biochemical processes involve
the cultivation of microbial, plant and animal cells
or biochemically active substances derived from such
cell cultures or organisms. Commonly, bioreactors are
cylindrical and vary in size. The design and components of
a typical bioreactor are shown in Fig. 10.1.
A bioreactor should ful??l the following requirements:
1. a sterile environment, so that a pure culture may be
grown without contamination
2. adequate supply of air for cellular respiration in
culture
3. uniform mixing of nutrients, cells and air throughout
the bioreactor vessel without causing any shear stress
to the cultured cells
Chapter 10_Bioprocessing and Bio-manuf.indd 233 23-01-2025 11:27:47
Reprint 2025-26
Page 4
Students are already aware that living organisms especially
microbes and biological processes therein are used for
making various household products (curd/yoghurt, idli,
kinema, etc.) and industrial products (ethanol). We have
already learnt in the previous class that living organisms
are endowed with a variety of metabolic processes which
lead to the formation of chemical compounds, called
metabolites, that are broadly classi??ed into primary
and secondary metabolites. Primary metabolites are the
compounds produced directly out of primary metabolic
pathways associated with essential cellular functions such
as growth and development. On the contrary, secondary
metabolites are intermediates or indirect products,
elaborated by entirely different metabolic pathways called
secondary metabolic pathways. Secondary metabolites take
part in a variety of functions. For example, they are used in
defence for protection against pathogens, phytoplanktons
and herbivores, to improve tolerance to abiotic stresses;
as attractants for insects and animals for fertilisation,
seed dispersal in plants or to contribute in causing the
displeasure to the unwanted feeders.
10.1 Historical
Perspective
10.2 Instrumentation
in Bioprocessing:
Bioreactor and
Fermenter Design
10.3 Operational Stages
of Bioprocess
10.4 Bioprocessing and
Biomanufacturing
of Desired Product
Bioprocessing and
Biomanufacturing
10
Chapter
Chapter 10_Bioprocessing and Bio-manuf.indd 231 23-01-2025 11:27:46
Reprint 2025-26
Biotechnology XII 232
Nowadays, most of these secondary metabolites have
a variety of applications in the form of pharmaceuticals,
dyes, food additives, enzymes, vitamins, etc. In view of the
variety of applications, production of these compounds
(biochemicals) at commercial level requires their production
in bulk quantities, as quantities produced naturally are
not suf??cient. These compounds are usually produced at
commercial level in a puri??ed form through a series of steps
covered under bioprocessing. For large scale production,
where large volume (on an average 100–10,000 litres) of
culture can be processed, the development of bioreactors
was required.
10.1 Historical Pers Pective After the breakthrough discovery of Penicillin and its
role in killing bacteria by Alexander Fleming in 1928,
the signi??cance of products from biological systems was
well understood. Now, the challenge before the scienti??c/
research community was to enhance the production
of penicillin. Production in larger amount for its use in
treatment would obviously require a systematic process
using the culture of biological entity in question, i.e.,
Penicillium species. The need of involvement of microbial
physiologist and other life scientists and technologists
was identi??ed. This followed the identi??cation of a number
of products of living organisms and processes especially
from microbes for application in bioprocessing. Many
companies and government laboratories, assisted by
different universities and institutions came together to
take up this challenge and efforts were made to increase
the production of penicillin. All this paved a way for the
emergence of a new area of biological applications, which
is now known as bioprocessing. Thus, bioprocessing
involves biological or living systems or their components
(e.g., enzymes, chloroplasts, etc.) and chemical engineering
processes to obtain the desired products at commercial
level as depicted in Fig. 10.4.
At industrial or commercial stage, all bioprocesses are
carried out in vessels called fermenter or bioreactor. We
are also aware that after the advent of rDNA technology,
Chapter 10_Bioprocessing and Bio-manuf.indd 232 23-01-2025 11:27:47
Reprint 2025-26
Bioprocessing and Biomanufacturing
233
Box 1
Discovery of Penicillin
It was in 1928 when Alexander Fleming
at St. Mary’s Hospital in London, while
trying to isolate boils causing bacterium,
Staphylococcus aureus, found that one of the
Petridishes was contaminated inadvertently
with a foreign entity. Instead of discarding
the Petri plate for disinfection, Fleming made
an important observation in the unwashed
contaminated plate that no bacteria grew near the invading entity. The observation surprised
Fleming’s intellect and he soon realised that this chance observation may be a meaningful
arena of interest.
Later this antibacterial foreign entity was identi??ed as a common mould, the Penicillium
notatum, and the metabolite secreted has powerful antibacterial properties called penicillin.
Its full potential as an effective antibiotic was established by Ernest Chain and Howard
Florey. This antibiotic was extensively used to treat the American soldiers wounded in World
War II. Fleming, Chain and Florey were awarded the Nobel Prize in 1945 for this discovery.
microbes are extensively employed for the production of a
number of biological material for the welfare of mankind.
10.2 i nstrumentation in Bio Processing :
Bioreactor and Fermenter d esign Bioreactor is an engineered vessel made up of glass or
steel that supports a biologically active environment,
where cells can be cultivated under aseptic conditions with
appropriate nutritional and environmental requirements.
In a bioreactor, the biochemical processes involve
the cultivation of microbial, plant and animal cells
or biochemically active substances derived from such
cell cultures or organisms. Commonly, bioreactors are
cylindrical and vary in size. The design and components of
a typical bioreactor are shown in Fig. 10.1.
A bioreactor should ful??l the following requirements:
1. a sterile environment, so that a pure culture may be
grown without contamination
2. adequate supply of air for cellular respiration in
culture
3. uniform mixing of nutrients, cells and air throughout
the bioreactor vessel without causing any shear stress
to the cultured cells
Chapter 10_Bioprocessing and Bio-manuf.indd 233 23-01-2025 11:27:47
Reprint 2025-26
Biotechnology XII 234
Exhaust
Air Sparger
Baf?e
Water
Outlet
Digital controller
Outlet for ir a
Agitator Shaft
Motor
Inoculation Port
Impeller
Water
Inlet
In
NaoH
Antifoam
In
HCl
Water
Bath
Temperature Probe
pH Probe
(a)
Fig. 10.1: (a) Diagrammatic representation of the design and components of a typical bioreactor
(b) Photograph of a laboratory bio-reactor
(b)
4. a system for maintenance of optimum temperature
conducive for the growth and product formation in a
desired culture
5. a system for monitoring the environmental process
parameters, such as pH, dissolved oxygen, etc.
Chapter 10_Bioprocessing and Bio-manuf.indd 234 23-01-2025 11:27:47
Reprint 2025-26
Page 5
Students are already aware that living organisms especially
microbes and biological processes therein are used for
making various household products (curd/yoghurt, idli,
kinema, etc.) and industrial products (ethanol). We have
already learnt in the previous class that living organisms
are endowed with a variety of metabolic processes which
lead to the formation of chemical compounds, called
metabolites, that are broadly classi??ed into primary
and secondary metabolites. Primary metabolites are the
compounds produced directly out of primary metabolic
pathways associated with essential cellular functions such
as growth and development. On the contrary, secondary
metabolites are intermediates or indirect products,
elaborated by entirely different metabolic pathways called
secondary metabolic pathways. Secondary metabolites take
part in a variety of functions. For example, they are used in
defence for protection against pathogens, phytoplanktons
and herbivores, to improve tolerance to abiotic stresses;
as attractants for insects and animals for fertilisation,
seed dispersal in plants or to contribute in causing the
displeasure to the unwanted feeders.
10.1 Historical
Perspective
10.2 Instrumentation
in Bioprocessing:
Bioreactor and
Fermenter Design
10.3 Operational Stages
of Bioprocess
10.4 Bioprocessing and
Biomanufacturing
of Desired Product
Bioprocessing and
Biomanufacturing
10
Chapter
Chapter 10_Bioprocessing and Bio-manuf.indd 231 23-01-2025 11:27:46
Reprint 2025-26
Biotechnology XII 232
Nowadays, most of these secondary metabolites have
a variety of applications in the form of pharmaceuticals,
dyes, food additives, enzymes, vitamins, etc. In view of the
variety of applications, production of these compounds
(biochemicals) at commercial level requires their production
in bulk quantities, as quantities produced naturally are
not suf??cient. These compounds are usually produced at
commercial level in a puri??ed form through a series of steps
covered under bioprocessing. For large scale production,
where large volume (on an average 100–10,000 litres) of
culture can be processed, the development of bioreactors
was required.
10.1 Historical Pers Pective After the breakthrough discovery of Penicillin and its
role in killing bacteria by Alexander Fleming in 1928,
the signi??cance of products from biological systems was
well understood. Now, the challenge before the scienti??c/
research community was to enhance the production
of penicillin. Production in larger amount for its use in
treatment would obviously require a systematic process
using the culture of biological entity in question, i.e.,
Penicillium species. The need of involvement of microbial
physiologist and other life scientists and technologists
was identi??ed. This followed the identi??cation of a number
of products of living organisms and processes especially
from microbes for application in bioprocessing. Many
companies and government laboratories, assisted by
different universities and institutions came together to
take up this challenge and efforts were made to increase
the production of penicillin. All this paved a way for the
emergence of a new area of biological applications, which
is now known as bioprocessing. Thus, bioprocessing
involves biological or living systems or their components
(e.g., enzymes, chloroplasts, etc.) and chemical engineering
processes to obtain the desired products at commercial
level as depicted in Fig. 10.4.
At industrial or commercial stage, all bioprocesses are
carried out in vessels called fermenter or bioreactor. We
are also aware that after the advent of rDNA technology,
Chapter 10_Bioprocessing and Bio-manuf.indd 232 23-01-2025 11:27:47
Reprint 2025-26
Bioprocessing and Biomanufacturing
233
Box 1
Discovery of Penicillin
It was in 1928 when Alexander Fleming
at St. Mary’s Hospital in London, while
trying to isolate boils causing bacterium,
Staphylococcus aureus, found that one of the
Petridishes was contaminated inadvertently
with a foreign entity. Instead of discarding
the Petri plate for disinfection, Fleming made
an important observation in the unwashed
contaminated plate that no bacteria grew near the invading entity. The observation surprised
Fleming’s intellect and he soon realised that this chance observation may be a meaningful
arena of interest.
Later this antibacterial foreign entity was identi??ed as a common mould, the Penicillium
notatum, and the metabolite secreted has powerful antibacterial properties called penicillin.
Its full potential as an effective antibiotic was established by Ernest Chain and Howard
Florey. This antibiotic was extensively used to treat the American soldiers wounded in World
War II. Fleming, Chain and Florey were awarded the Nobel Prize in 1945 for this discovery.
microbes are extensively employed for the production of a
number of biological material for the welfare of mankind.
10.2 i nstrumentation in Bio Processing :
Bioreactor and Fermenter d esign Bioreactor is an engineered vessel made up of glass or
steel that supports a biologically active environment,
where cells can be cultivated under aseptic conditions with
appropriate nutritional and environmental requirements.
In a bioreactor, the biochemical processes involve
the cultivation of microbial, plant and animal cells
or biochemically active substances derived from such
cell cultures or organisms. Commonly, bioreactors are
cylindrical and vary in size. The design and components of
a typical bioreactor are shown in Fig. 10.1.
A bioreactor should ful??l the following requirements:
1. a sterile environment, so that a pure culture may be
grown without contamination
2. adequate supply of air for cellular respiration in
culture
3. uniform mixing of nutrients, cells and air throughout
the bioreactor vessel without causing any shear stress
to the cultured cells
Chapter 10_Bioprocessing and Bio-manuf.indd 233 23-01-2025 11:27:47
Reprint 2025-26
Biotechnology XII 234
Exhaust
Air Sparger
Baf?e
Water
Outlet
Digital controller
Outlet for ir a
Agitator Shaft
Motor
Inoculation Port
Impeller
Water
Inlet
In
NaoH
Antifoam
In
HCl
Water
Bath
Temperature Probe
pH Probe
(a)
Fig. 10.1: (a) Diagrammatic representation of the design and components of a typical bioreactor
(b) Photograph of a laboratory bio-reactor
(b)
4. a system for maintenance of optimum temperature
conducive for the growth and product formation in a
desired culture
5. a system for monitoring the environmental process
parameters, such as pH, dissolved oxygen, etc.
Chapter 10_Bioprocessing and Bio-manuf.indd 234 23-01-2025 11:27:47
Reprint 2025-26
Bioprocessing and Biomanufacturing
235
Thus, in order to ful??l these requirements a typical
bioreactor consists of the following:
• Agitator shaft: It helps in mixing contents of the
bioreactor and keeps the cells in perfect homogenous
conditions that provide better transport of nutrient
and oxygen throughout the running bioprocess. An
impeller is ??xed at the bottom of an agitator shaft.
• Sparger: It helps in providing an adequate and
continuous supply of sterilised air (oxygen) using
micro??lters for growing cells submerged in the liquid
media inside the bioreactor system.
• Baffle: It helps in breaking the vortex formation, which
is highly undesirable as it changes the centre of gravity
of the system making it consume extra power to run
the system.
• Jacket: It provides area for the circulation of water
at the given temperature for maintenance of optimum
temperature inside the device required for the growth
of cultivated cells and product formation.
• Sensitivity probe for temperature and pH: These
are the probes to sense temperature and hydrogen ion
concentration of a bioprocess.
• Digital controller for controlling process
parameters: Digital controller is connected to
bioreactor through probes and its one separate unit is
connected to a water bath that pumps water of desired
temperature in and out of the jacket present around
the bioreactor unit for the maintenance of temperature
throughout. It is also connected to pH probes and
bottles containing 1M NaOH and 1N HCl. As the
probe senses acidity or alkalinity, digital controller
commands any of the two bottles for addition of either
dilute NaOH or HCl for the maintenance of the desired
pH. All process parameters including temperature,
pH, speed of stirring (rpm), etc., are exhibited over the
display of the controller.
10.2.1 Types of bioreactors
On the basis of the design or con??guration, important
types of bioreactors are discussed below:
• Stirred tank reactors are the most conventional
bioreactors. In these reactors, agitator facilitates the
Chapter 10_Bioprocessing and Bio-manuf.indd 235 23-01-2025 11:27:47
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