Scale up of a viscous fungal fermentation: Application of scale-up criteria with regime analysis and operating boundary conditions
Article first published online: 24 JUL 2006
Copyright © 2006 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 96, Issue 2, pages 307–317, 1 February 2007
How to Cite
Pollard, D.J., Kirschner, T.F., Hunt, G.R., Tong, I.-T., Stieber, R. and Salmon, P.M. (2007), Scale up of a viscous fungal fermentation: Application of scale-up criteria with regime analysis and operating boundary conditions. Biotechnol. Bioeng., 96: 307–317. doi: 10.1002/bit.21112
- Issue published online: 23 DEC 2006
- Article first published online: 24 JUL 2006
- Manuscript Accepted: 29 JUN 2006
- Manuscript Received: 13 MAR 2006
- scale up;
- Glarea lozoyensis;
- regime analysis;
- mixing time
The scale up of the novel, pharmaceutically important pneumocandin (B0), from the filamentous fungus Glarea lozoyensis was successfully completed from pilot scale (0.07, 0.8, and 19 m3) to production scale (57 m3). This was accomplished, despite dissimilar reactor geometry, employing a combination of scale-up criteria, process sensitivity studies, and regime analysis using characteristic time constants for both oxygen mass transfer and bulk mixing. Dissolved oxygen tension, separated from the influence of agitation by gas blending at the 0.07 m3-scale, had a marked influence on the concentrations of pneumocandin analogs with different levels of hydroxylation, and these concentrations were used as an indicator of bulk mixing upon scale up. The profound impact of dissolved oxygen tension (DOT) (low and high levels) on analog formation dictated the use of constant DOT, at 80% air saturation, as a scale-up criterion. As a result kLa, Oxygen uptake rate (OUR) and hence the OTR were held constant, which were effectively conserved across the scales, while the use of other criterion such as Pg/VL, or mixing time were less effective. Production scale (57 m3) mixing times were found to be faster than those at 19 m3 due to a difference in liquid height/tank diameter ratio (HL/DT). Regime analysis at 19 and 57 m3 for bulk mixing (tc) and oxygen transfer (1/kLa) showed that oxygen transfer was the rate-limiting step for this highly shear thinning fermentation, providing additional support for the choice of scale-up criterion. Biotechnol. Bioeng. 2007;96: 307–317. © 2006 Wiley Periodicals, Inc.