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Scale up of fermentation
Dr. Pavan J Kundur, M.Sc., Ph.D.,
Assistant Professor
Department of Biotechnology
P C Jabin Science College,
Hubballi, Karnataka, India
Scaleup•Scale up studies refers to the act of using
results obtained from laboratory studies for
designing a prototype and a pilot plant
process; construction a pilot plant and using
pilot plant data for designing and
constructing a full scale plant.
Scale up
Scale up
Why conduct Scale up Studies?
• A pilot plant allows investigation of a product and process
on an intermediate scale before large amounts of money
are committed to full-scale production.
• It is usually not possible to predict the effects of a many-
fold increase in scale.
• Scale up studies are studies carried out at the laboratory or
even pilot plant scale fermentors to yield data that could
be used to to extrapolate and build the large scale
industrial fermentors with sufficient confidence it will
function properly with all its behaviours anticipated.
Importance of scale up studies
• More important during scale up exercises is that we are trying
to build industrial size fermentor capable or close of producing
the fermentation products as efficient as those produced in
small scale fermentors.
• It must be appreciated as the size of fermentation increases
during scale up various parameters measured might not show
a predictable linear co-relationships. Certain parameters
changes. Some remained constant. Some parameters need to
be modified and adjusted during scale up studies. The
objective is to try to get the same fermentation efficiency as
obtained in small scale fermentors at the most economical
values.
•Determining the various operational parameters
for optimized oxygen supply to the fermentation
process.
•Selection of optimum operative modes of the
fermentor
•Determining the changes in rheological properties
and its effect on the fermentation process.
•Modeling and formulation of process controls
•Sensors and controls
There are few crucial studies which will only be
answered by carrying it out on the pilot plant such
as:
Steps in Scale-Up
• Define product economics based on projected market size and
competitive selling and provide guidance for allowable
manufacturing costs
• Conduct laboratory studies and scale-up planning at the same time
• Define key rate-controlling steps in the proposed process
• Conduct preliminary larger-than-laboratory studies with equipment
to be used in rate-controlling step to aid in plant design
• Design and construct a pilot plant including provisions for process
and environmental controls, cleaning and sanitizing systems,
packaging and waste handling systems, and meeting regulatory
agency requirements
• Evaluate pilot plant results (product and process) including process
economics to make any corrections and a decision on whether or
not to proceed with a full scale plant development
INITIAL SCALE UP STUDIES
Most scale up studies are usually carried at different phases
involving different scales of fermentors.
Preliminary work are carried out at the level of petri dishes and small
scale laboratory fermentors to establish whether the process is
technically viable, meaning it is possible to produce such
fermentation process and the products on the small scale.
Additional parameters not provided by petri dishes studies and for
more confidence are obtained by carrying further studies using
submerged liquid fermentation using various sizes laboratory scale
fermentors and even a pilot plant fermentor.
Rules followed while doing scale-up
• There are a few rules of the thumb followed when doing scale
up studies such as:
1. Similarity in the geometry and configuration of fermentors
used in scaling up
•
2. A minimum of three or four stages of increment in the
scaling up of the volume of fermentation studies. Each jump in
scale should be by a magnitude or power increase and not an
increase of a few litres capacity. Slight increase in the working
volume would not yield significant data for scale up operation
A pilot plant can be used for
• Evaluating the results of laboratory studies and making
product and process corrections and improvements
• Producing small quantities of product for sensory,
chemical, microbiological evaluations, limited market
testing or furnishing samples to potential customers,
shelf-live and storage stability studies
• Determining possible salable by-products or waste
stream requiring treatment before discharge
• Providing data that can be used in making a decision on
whether or not to proceed to a full-scale production
process; and in the case of a positive decision, designing
and constructing a full-size plant or modifying an
existing plant
Studies carried out during scale up
1. Inoculum development
2. Sterilization establishing the correct sterilization
cycle at larger loads
3. Environmental parameters such as nutrient
availability, pH, temperature, dissolved
oxygen, dissolved carbon dioxide,
4. Shear conditions, foam production
Thank You

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Fermentation -- Scale up Technology

  • 1. Scale up of fermentation Dr. Pavan J Kundur, M.Sc., Ph.D., Assistant Professor Department of Biotechnology P C Jabin Science College, Hubballi, Karnataka, India
  • 2. Scaleup•Scale up studies refers to the act of using results obtained from laboratory studies for designing a prototype and a pilot plant process; construction a pilot plant and using pilot plant data for designing and constructing a full scale plant.
  • 5. Why conduct Scale up Studies? • A pilot plant allows investigation of a product and process on an intermediate scale before large amounts of money are committed to full-scale production. • It is usually not possible to predict the effects of a many- fold increase in scale. • Scale up studies are studies carried out at the laboratory or even pilot plant scale fermentors to yield data that could be used to to extrapolate and build the large scale industrial fermentors with sufficient confidence it will function properly with all its behaviours anticipated.
  • 6. Importance of scale up studies • More important during scale up exercises is that we are trying to build industrial size fermentor capable or close of producing the fermentation products as efficient as those produced in small scale fermentors. • It must be appreciated as the size of fermentation increases during scale up various parameters measured might not show a predictable linear co-relationships. Certain parameters changes. Some remained constant. Some parameters need to be modified and adjusted during scale up studies. The objective is to try to get the same fermentation efficiency as obtained in small scale fermentors at the most economical values.
  • 7. •Determining the various operational parameters for optimized oxygen supply to the fermentation process. •Selection of optimum operative modes of the fermentor •Determining the changes in rheological properties and its effect on the fermentation process. •Modeling and formulation of process controls •Sensors and controls There are few crucial studies which will only be answered by carrying it out on the pilot plant such as:
  • 8. Steps in Scale-Up • Define product economics based on projected market size and competitive selling and provide guidance for allowable manufacturing costs • Conduct laboratory studies and scale-up planning at the same time • Define key rate-controlling steps in the proposed process • Conduct preliminary larger-than-laboratory studies with equipment to be used in rate-controlling step to aid in plant design • Design and construct a pilot plant including provisions for process and environmental controls, cleaning and sanitizing systems, packaging and waste handling systems, and meeting regulatory agency requirements • Evaluate pilot plant results (product and process) including process economics to make any corrections and a decision on whether or not to proceed with a full scale plant development
  • 9. INITIAL SCALE UP STUDIES Most scale up studies are usually carried at different phases involving different scales of fermentors. Preliminary work are carried out at the level of petri dishes and small scale laboratory fermentors to establish whether the process is technically viable, meaning it is possible to produce such fermentation process and the products on the small scale. Additional parameters not provided by petri dishes studies and for more confidence are obtained by carrying further studies using submerged liquid fermentation using various sizes laboratory scale fermentors and even a pilot plant fermentor.
  • 10. Rules followed while doing scale-up • There are a few rules of the thumb followed when doing scale up studies such as: 1. Similarity in the geometry and configuration of fermentors used in scaling up • 2. A minimum of three or four stages of increment in the scaling up of the volume of fermentation studies. Each jump in scale should be by a magnitude or power increase and not an increase of a few litres capacity. Slight increase in the working volume would not yield significant data for scale up operation
  • 11. A pilot plant can be used for • Evaluating the results of laboratory studies and making product and process corrections and improvements • Producing small quantities of product for sensory, chemical, microbiological evaluations, limited market testing or furnishing samples to potential customers, shelf-live and storage stability studies • Determining possible salable by-products or waste stream requiring treatment before discharge • Providing data that can be used in making a decision on whether or not to proceed to a full-scale production process; and in the case of a positive decision, designing and constructing a full-size plant or modifying an existing plant
  • 12. Studies carried out during scale up 1. Inoculum development 2. Sterilization establishing the correct sterilization cycle at larger loads 3. Environmental parameters such as nutrient availability, pH, temperature, dissolved oxygen, dissolved carbon dioxide, 4. Shear conditions, foam production