vaccines. The bioreactors were filled
to 15mL for culture
and were then set
to stir at low speed
16 hours, to allow
initial cell attachment and spreading.
24 hours and cell
growth on the mi-
observed by micros-
copy. The results
showed that the
Vero cell achieved
using continuous or
and grew well on
and had attained
confluence by day four of culture. (Figure 3).
These studies show that using the ambr
system’s unique stirring capability and automated pipetting; microcarriers can automatically be consistently distributed across each
bioreactor. Additionally, cells can attach and
propagate well. This means that scientists
can rapidly assess up to 24 cell-specific culture parameters in parallel, simultaneously
including stirring speed, media formulation
or feed strategies to determine the optimum
conditions for cell attachment, growth rate
and vaccine titre, for example.
In summary, stirred, sparged microbioreactor technology can provide a good method
of developing optimal process development
for propagating cells on microcarriers in
vaccine production. Setting up and running
benchtop vessels and spinner flasks is
manually intensive, while the ambr microbioreactor is more convenient and takes far
less time to operate. This reduces reliance
on spinner flasks and benchtop bioreactors
and means process development for vaccine
manufacture can be performed more quickly
and efficiently, as well as increases the number of parameters that can be evaluated.
Being able to assess so many different pa-
Fig. 3. Vero cells propagated on microcarriers in ambr bioreactors.
Fig. 2. Consistency of microcarrier addition across 6 ambr vessel replicates
rameters and perform process development
in weeks rather than months may save valuable time and thus, utilisation of the ambr
system could make a significant contribution
where more affordable vaccines or a rapid
response to unexpected situations such as a
pandemic threat is critical. ■
 Kresse H, Shah M. (2010) Strategic
trends in the vaccine market.Nat Rev Drug
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S, Trombetta C, Mennitto E, Manini I,
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cells: a new horizon for vaccine produc-
tion.Expert Rev Vaccines. 11( 5):587-94
[ 3] Genzel Y, Dietzsch C, Rapp E, Schwarzer
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Cytotechnology 64, ( 6), 667-78
ambr bioreactors in each workstation station
was filled with a Cytodex® 1 microcarrier (GE
Healthcare) stock suspension (40g/L) and
stirred at 300rpm. The workstation was set
to dispense microcarrier amounts (2g/L 3g/L
4g/L 5g/L and 6g/L) from this microcarrier
stock bioreactor to the others within the
culture station. The uniformity of dispensing was measured across 6 ambr bioreactor
replicates. The results (Figure 2) showed
the weight of microcarriers dispensed is
consistent with a CV<1% of the amount programmed to be dispensed. This indicates
that the ambr system can reliably and consistently dispense microcarriers from two
‘stock’ vessels to the other 22 micro bioreactor vessels for the cell culture phase.
CELL ATTACHMENT AND CULTURE
To demonstrate that the ambr system can
support cell attachment and propagation
on microcarriers, Cytodex 1 microcarriers
and Vero cells (ATCC® CL-160™) were added
to ambr bioreactors, to provide 2g/L microcarriers and 1.5x105/mL cells in a 6mL
volume for seeding. Vero cells were chosen
as these cells are commonly used attachment dependent cells in the production of