Scale up Principles

Microbial Genetics

Introduction
Most
common phrases are there in fermentation technology 'Scaling up' and 'Scaling down' studies.

'scaling up' is more commonly understood and practiced during the designing of industrial scale fomenters. Whereas 'scaling down' studies are rarely heard that frequent.

 fermentation process is used with the ultimate objective of producing the fermentation products on the level of industrial scale.

Products need to be produced at large volume so that the process is economically viable. This requires scaling up.
We do scaling up studies to ensure that the fermentation process is technically and economically viable to be produced in the end at a large scale
3

Scale up studies
carried out at the laboratory or even pilot plant scale fermentors to build the large scale industrial fermentors.
More important during scale up exercises you are trying to build industrial size fermentor capable or close of producing the fermentation products as efficient as those produced in small scale fermentors.

Small Scale Applications

Laboratory Bench top equipment for discovery or process development, typically under 30 liters

Pilot Scale Applications :-

Pilot Skid mounted equipment for scale up studies, process optimization, or small volume production. Typically under 2000 liters

10

Bioreactor scale-up
Once a particular bioprocess is accomplished successfully in laboratory scale experiments, the values of the operating variables and the physical properties are known or can be measured. The bioprocess is then usually carried out in a number of bioreactors of increasing scale, the final process optimization being performed at pilot plant scale (50 to 300 L of volume) where the operational conditions and the hydrodynamic and mixing are very similar to those used in the production scale.
11

The scale-up ratio is typically about 1:10 for bioprocesses, lower ratios decrease the performance on scale-up. risk of unexpected

It can be done according to four different approaches, as widely recognized:

1. 2. 3. 4.

fundamental methods; semi fundamental methods; dimensional analysis; rules of thumb.

12

1. Fundamental methods.........
based on the application of mathematical models for description of the influence of operational conditions and geometrical design of the bioreactor on the flow pattern in the bioreactor. In recent years, computational fluid dynamics has shown to be an effective tool to study the hydrodynamics of reactors and scale-up of bioprocesses (Dhanasekharan et al., 2005).

13

Cont............
These methods are very complicated, and frequently, many simplifications are required (Vasconcelos et al., 1998; Nedeltchev et al., 1999).
but, development of fundamental models able to describe the key characteristics of the system is perhaps the most helpful tool for successful scale-up and for the determination of the optimal conditions at the production scale

14

2. Semi-fundamental methods
where simplified equations are applied to obtain a practical approximation to the bioprocess operation. The parameters obtained will be scale dependent, and thereby the influence of scale on the process can be examined by model simulations. However, despite the extensive simplification of the problem when moving from the fundamental to semifundamental models, the complexity of the method is still substantial.
15

3. Dimensional analysis
based on keeping the values of dimensionless groups of parameters constant during the scale-up.

The dimensionless groups used are ratios of rates or time constants for the different mechanisms involved in bioprocess.

16

if all the dimensionless groups are kept constant, the relative importance of the mechanisms or phenomena involved in the process will not change during scale-up. It is often impossible to keep all the dimensionless groups constant during scale-up, hence one has to determine the most important groups and deemphasize the rest.

17

4. The Rule of thumb method

The rule of thumb method is the most common method. The scaleup criterion most used and percentage of each criteria used in the fermentation industry are: a) b) constant specific power input, constant volumetric mass transfer coefficient, KLa

18

a) b)

constant impeller tip speed of the agitator or shear constant dissolved oxygen concentration, CO2, (20%) (Margaritis and Zajic, 1978).

The different scale-up criteria normally result in entirely different process conditions on a production scale.

19

PROBLEMS ASSOCIATED WITH SCALE-UP

effects of fermentation size on process productivity and include a number of major and minor areas. Variations in the biomass formed

Large scale inoculum development

Medium sterilization Aeration Agitation
20

Heat removal Moisture content of the soIids pH control Contamination control Heterogeneity Downstream processing

Waste management Solid handling

21

Thank You
22