Biomedical Engineering Reference
In-Depth Information
9.
Biotechnol Bioeng
. 2010 Aug 15;
106(6):906-17. Production of cell
culture (MDCK) derived live
attenuated influenza vaccine
(LAIV) in a fully disposable
platform process. George M,
Farooq M, Dang T, Cortes B, Liu
J, Maranga L. Cell Culture
Development, MedImmune,
3055 Patrick Henry Dr., Santa
Clara, California 95054.
The majority of influenza vaccines are manufactured
using embryonated hens' eggs. The potential
occurrence of a pandemic outbreak of avian
influenza might reduce or even eliminate the supply
of eggs, leaving the human population at risk. Also,
the egg-based production technology is intrinsically
cumbersome and not easily scalable to provide a
rapid worldwide supply of vaccine. In this
communication, the production of a cell culture
(Madin-Darby canine kidney (MDCK)) derived live
attenuated influenza vaccine (LAIV) in a fully
disposable platform process using a novel Single Use
Bioreactor (SUB) is presented. The cell culture and
virus infection was maintained in a disposable
stirred tank reactor with PID control of pH, DO,
agitation, and temperature, similar to traditional
glass or stainless steel bioreactors. The application of
this technology was tested using MDCK cells grown
on microcarriers in proprietary serum-free medium
and infection with 2006/2007 seasonal LAIV strains
at 25-30 L scale. The MDCK cell growth was optimal
at the agitation rate of 100 rpm. Optimization of this
parameter allowed the cells to grow at a rate similar
to that achieved in the conventional 3 L glass
stirred-tank bioreactors. Influenza vaccine virus
strains, A/New Caledonia/20/99 (H1N1 strain), A/
Wisconsin/67/05 (H3N2 strain), and B/
Malaysia/2506/04 (B strain) were all successfully
produced in SUB with peak virus titers > or =8.6
log(10) FFU/mL. This result demonstrated that more
than 1 million doses of vaccine can be produced
through one single run of a small bioreactor at the
scale of 30 L and thus provided an alternative to the
current vaccine production platform with fast
turnaround and low up-front facility investment,
features that are particularly useful for emerging and
developing countries and clinical trial material
production.
