Development of a scaled-down aerobic fermentation model for scale-up in recombinant protein vaccine manufacturing.
A simple approach to the development of an aerobic scaled-down fermentation model is presented to obtain more consistent process performance during the scale-up of recombinant protein manufacture. Using a constant volumetric oxygen mass transfer coefficient (k(L)a) for the criterion of a scale-down process, the scaled-down model can be "tuned" to match the k(L)a of any larger-scale target by varying the impeller rotational speed. This approach is demonstrated for a protein vaccine candidate expressed in recombinant Escherichia coli, where process performance is shown to be consistent among 2-L, 20-L, and 200-L scales. An empirical correlation for k(L)a has also been employed to extrapolate to larger manufacturing scales.
Bioprocess Research and Development, Sanofi Pasteur, Toronto, Canada M2R 3T4. patrick.farrell@sanofipasteur.com
Patrick
P
Farrell
Jacob
J
Sun
Meg
M
Gao
Hong
H
Sun
Ben
B
Pattara
Arno
A
Zeiser
Tony
T
D'Amore
D000332:Aerobiosis; D019149:Bioreactors / Q000382:microbiology; D001709:Biotechnology / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D005285:Fermentation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013678:Technology, Pharmaceutical / Q000379:methods*; D014614:Vaccines, Synthetic / Q000096:biosynthesis* / Q000235:genetics
D011994:Recombinant Proteins; D014614:Vaccines, Synthetic