ThermoFisherScientific_Jan2021_ADeepDiveInto - 7

A Deep Dive into Perfusion Media for Bioprocessing Applications

Improved Quality

Speed to market

Improved lot control-Option to logically define lots
reduces process risk.

Potential for faster production of clinical doses-
Perfusion can generate significant product volume
with only minor process scale-up. This can reduce
time and effort needed to generate enough doses
for clinical testing.

Process control-Lower product retention time and
the potential to run a continuous operation allows
for better process control and minimal delay through
product production, refinement, and completion.

Better process control-Easier achievement
of consistent quality can lead to faster process
development.

Types of Perfusion
In general, there are four primary operation modes for suspension cell culture perfusion: N-1 perfusion,
concentrated fed-batch, intensified fed-batch, and continuous perfusion.

N-1 perfusion
Also called intensified seed train, N-1 perfusion is
used to achieve high cell densities while maintaining
logarithmic growth (Figure 1). This is a short-duration
(usually 4-7 days) method that is used to reduce the
number of vessels required in a seed train, allow for
higher-density reactor seeding, or generate highdensity seed banks. Productivity is not usually
a consideration.

Features of N-1 Perfusion
* Easy to run
* Less equipment needed
* Less characterization needed to
*
*

N-1 medium comparison: perfusion vs. fed-batch

*
*

80.0
Clone A

VCD (x 10 6 cells/mL)

70.0

Clone B

60.0

CDCHO clone A

50.0
40.0

30.0

20.0

optimize medium
Generates high cell density quickly
Medium exchange rate intended to
" stay ahead of cell demand " to maintain
logarithmic growth
Duration of run is short (4-7 days)
May reduce the number of vessels in
the seed train
Provides higher seeding density to
production reactors
May be used to generate high cell
density banks
Does not require high productivity

10.0
0.0

Days

Figure 1. Operation of two clones in Gibco™ High-Intensity
Perfusion CHO Medium, compared to operation in a fed-batch
medium. Faster cell growth and higher viable cell density (VCD)
are achieved with N-1 perfusion.
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