An introduction to a novel
filtration system
ATF
-
manufacturing Platform
Upstream Unit Operations
ATF
-
cellcultivation
Concentrated Perfusion
Concentrated Fed
-
Batch
Hybrid Processes
2
Capacity cannot be calculated solely by bioreactor size
10kg
500g
1000L
3kg
150g
300L
1kg
50g
100L
20 Runs/Yr
Per Run
*
Fed
-
Batch
150kg
15kg
500g
1000L
45kg
4.5kg
150g
300L
15kg
1.5kg
50g
100L
10 Runs/Yr
30 Day Run
Per Day
*
Perfusion
* 500 mg/L post purification yield
15x more product
in the same time!
Avid Bioservices Facilities
Why use Perfusion in Research, even if not later...
•
Perfusion produces more material in a shorter time period
–
Do you have time to make a new cell line?
–
Do you have time to develop a special media?
•
Pre
-
clinical material can be produced faster with less development effort
•
A low producing cell line can be used to produce enough material in a
shorter time for a phase 1 trial
•
Smaller bioreactors are required at all stages of PD and Manufacturing
-
saving significant capital cost
•
One continuous culture experiment can perform multiple metabolic studies to
understand clone behavior in different design spaces, significantly faster
than in batch or fed
-
batch
•
Upstream development times may be reduced due to simpler feeding
Perfusion and Concentrated Perfusion
•
Perfusion is
dead
-
Long Live
Concentrated
Perfusion !!
•
What
is
Concentrated
Perfusion?
–
Only
possible
with the ATF
–
Ultra
-
high
viable
cell
densities
, in the region of
60
-
150m
/ ml
–
Requires
1
-
3
vv
/
day
media (not
more
)
–
Same
simple process
control
as
perfusion
& CFB
–
but
higher
productivity
•
When
should
perfusion
be
used
and not
Concentrated
Perfusion?
–
When
the
product
quality
is
affected
by cell
concentration
, or
if
protein
expression
depends
on a
dilute
toxic
species
Concentrated
Perfusion
•
“Standard” perfusion application but with the ATF System
–
high cell concentration
(60
-
100m/ml), 30
-
60 days
•
Straight
-
forward
feeding
control
,
removal of
metabolites
& proteins
•
Continuous
filtered
harvests
,
often
pooled
(
every
3
-
6
days
) for
easier
DSP
–
~0.1g/L/day per 10m cells /ml for an average cell line (10pg/cell/day at 2vvd)
M
F
filter
retains
cells inside
reactor while
molecules filter
through
Filtrate pump runs
at 0.5
-
3 vv / day
or as required by
cell growth
ATF rate constant
at minimum
~0.05
-
0.1 vv /
min
Feeding
controlled by
level probe
Graph taken from Genetic Engineering News October 2007
CHO Perfusion Results
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Preparing document for printing…
0%
Comments 0
Log in to post a comment