TUTORIAL
Bioprocessing
Additionally, a variety of reports can be
generated for each run to meet current Good
Manufacturing Practices regulatory requirements. The system also has remote alarm
capabilities.
The perfusion-based feeding strategy can
control the feed rate of the system from 0.1
mL/min to many mL/min. Gas exchange and
temperature are controlled by the system.
Metabolite concentrations can be measured
at separate sampling ports for both the intracapillary and extracapillary loops.
This control of the perfusion feeding
system can minimize the use of expensive
media and improve cell quality by reducing
cell stress resulting from excessive metabolite concentrations. A diagram depicting the
control of metabolites including glucose and
lactate in the Quantum system versus a typical fask-based or batch-fed process is shown
in Figure 1.
The surface area of the hollow-fber bioreactor is 2.1 square meters or approximately
equal to that of a 40 layer cell stack. An individual device is capable of producing more
than two billion cells depending upon cell type.
Scaleup to larger lot sizes is possible because of
the increased reproducibility and reduced manpower required to run multiple systems.
A skilled operator can manage up to 10
devices simultaneously. That translates to a
lot size of over 20 square meters and over
20 billion cells per lot. The reduced footprint
and ease of use of the system translates to
an increased ability to meet the scale-up requirements of cell therapy manufacturing.
For example: a cell therapy requiring the
rather low dose of fve million cells per dose
(Table 2). The system could produce 400
doses per device per lot. For a therapeutic
indication present in two percent of the U.S.
population over the age of 65, more than
2,000 lots would be required to reach all the
patients. A laboratory with four full-time employees and 40 systems could produce all of
the cells required for an entire year.
Adoption of the Quantum system is simplifed by the use of predefned tasks for each
step of the culture process. Each run can be
fully documented for regulatory purposes
by the generation of electronic records, user
authentication, and remote alarming capa-
bilities. Feeding and waste removal are precisely controlled by the perfusion system of
the hollow fbers eliminating the big swings
in nutrients and waste products common to
batch-fed and fask-based cultures.
James Beltzer, Ph.D. (jim.beltzer@
terumobct.com), is senior cell processing
specialist at Terumo BCT.
Website: www.terumobct.com.
Figure 1. Comparison of metabolite variation in
the Quantum system compared to a fask-based
system over nine days of growth.
Manufacturing Requirements
Cells/Dose
5 x 106
Lot Size
2 x 109
Dose/Lot
400
U.S. Population
Over 65
314 M
41,750,000
Potential Patient Pool (2%)
835,000
Lots to Support
Patient Population
>2,000
Table 2. Manufacturing requirements to reach a
patient population as determined by lot size.
Genetic Engineering & Biotechnology News
|
GENengnews.com | September 1, 2013
|
43