InPro 5000i CO2 Sensor

Product Launch
Urdorf, January 2012

Market Situation
Mettler Toledo is market leader in in-line process analytics in
BioPharma for pH and DO

CO2 measurement is of interest for ~10 % of the customers mainly in

fed-batch or perfusion applications

Mammalian cell cultures

Algae cultures

Most customers do not have in-line CO2 measurement because

-

Today's technology is
Not reliable
expensive (high consumable cost)
complicated due to sample handling (BGA)

The new InPro 5000i offers attractive additional business in

the Biopharma Industy

METTLER TOLEDO's new InPro 5000i is a superior solution for

in-line CO2 measurement. And complementary to pH and DO.
1

Internal usage only

Application Fermentation
Aux Upstream

Downstream

Applications

Mainly mammalian cell fermentation

Sometimes algae cultures
Reasons for CO2 measurement

Avoid toxic levels of CO2

Carbon source control
Control Nutrient feeding
Typical conditions & requirements

Small to large bioreactors

Sterilization in-situ or autoclave
Fed-batch or continuous operation
FDA compliant materials
Slow process - long batch duration

Only if the customer identified CO2 as a critical parameter, in-line

measurement is beneficial
2

Internal usage only

Benefits of In-Line CO2 Control in Cell Cultures

R&D
Understanding
metabolism
Optimizing growth
conditions

Scale-up & Process

Development
Further data on mass
balance
Developing data for
stop criteria
Faster time to market

Production
Optimize yield (40 % higher
yield is reported)
Immediate reaction on
abnormal CO2 concentration
Control of C-source or
nutrients based on CO2 level

Internal usage only

Best growth conditions

Too high

- Can be toxic for the cell

- Influences the cell metabolism
=> inhibits specific growth

Optimum
Range
Too low

CO2 concentration

Growth rate

Effect of Optimal CO2 Control in Cell Cultures

Can slow down some

metabolic processes
=> inhibits specific growth
time

Accurate CO2 control can significantly increase yield and

shorten fermentation time
4

Internal usage only

Semi-Continuous Mode: Fed-Batch Fermentation

Substrate

acid

alkaline

Substrate is added in increments as

the fermentation progresses
Substrate is controlled according to
process needs
Higher cell density and yield can be
achieved compared to batch mode

air

pH

DO

TRB

CO2

CO2 measurement allows the control

of substrate feeding
Control prevents toxic levels of CO2

Accurate in-line measurement is necessary for continuous

process control
5

Internal usage only

Key customer for in-line CO2 Measurement

Mammalian cell culture

Algae fermentation

Internal usage only

Challenging Scenarios with CO2 customers

Usual situation after a successful trial at Bio customer (GMP)

Customer has tested the CO2 measurement: Everything worked fine

However

Customer (GMP) is challenged on how he can leverage the value to improve

his process!

Drive the customer (GMP) to go for the next step?

Encourage the customer to reengineer his fermentation trough the process

development. Establish the best possible level of CO2 at every single
fermentation step because:
By maintaining the optimized CO2 level during the whole
fermentation
- the yield can be increased by up to 40% (reported by other customers)
- fermentation time can be shortened since critical level of CO2 reduces
growth rate
- reproducibility of the process can be significantly improved

Reengineering of the process based on an accurate CO2 control

can significantly increase process efficiency (more output $)
7

Internal usage only