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Integration of host strain bioengineering and bioprocess development using ultra-scale down studies to select the optimum combination: an antibody fragment primary recovery case study.

Aucamp JP, Davies R, Hallet D, Weiss A, Titchener-Hooker NJ - Biotechnol. Bioeng. (2014)

Bottom Line: The ability of cells to resist breakage was dependant on a combination of factors including host strain, vector, and fermentation strategy.The use of scale-down primary recovery process sequences can be used to screen a larger number of engineered strains.This can lead to closer integration with and better feedback between strain development, fermentation development, and primary recovery studies.

View Article: PubMed Central - PubMed

Affiliation: Bioprocess Research and Development, Novartis Phama AG, Basel, Switzerland. jean.aucamp@novartis.com.

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Related in: MedlinePlus

The USD centrifugation mimic was used to predict clarification levels for centrifugation operations and compared to pilot scale results. A: Dewatering clarification studies of harvest broth from three fermentation processes compare well for pilot and USD scales. The feed streams were: Feed 9 USD (□) and pilot scale (▪), Feed 2 USD (◊) and pilot scale (♦) and Feed 8 USD (○) and pilot scale (●). B: Clarification studies of conditioned extract compare well for USD and pilot scales. The feed streams were Feed 2 USD (◊) and pilot scale (♦), Feed 9 USD (□) and pilot scale (▪), Feed 6 USD (▿) and pilot scale (▾) and Feed 8 USD (○) and pilot scale (●).
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fig03: The USD centrifugation mimic was used to predict clarification levels for centrifugation operations and compared to pilot scale results. A: Dewatering clarification studies of harvest broth from three fermentation processes compare well for pilot and USD scales. The feed streams were: Feed 9 USD (□) and pilot scale (▪), Feed 2 USD (◊) and pilot scale (♦) and Feed 8 USD (○) and pilot scale (●). B: Clarification studies of conditioned extract compare well for USD and pilot scales. The feed streams were Feed 2 USD (◊) and pilot scale (♦), Feed 9 USD (□) and pilot scale (▪), Feed 6 USD (▿) and pilot scale (▾) and Feed 8 USD (○) and pilot scale (●).

Mentions: Pilot scale dewatering (Fig. 3A) and extract clarification (Fig. 3B) were performed for harvested material from several different feed streams and the USD clarification prediction studies conducted in parallel. For both centrifugation steps the USD predictions provided a good estimate of the actual clarification levels obtained in the pilot centrifuge. The USD dewatering level was fixed at 66.7% by removing supernatant equal to two-thirds of total volume before resuspension.


Integration of host strain bioengineering and bioprocess development using ultra-scale down studies to select the optimum combination: an antibody fragment primary recovery case study.

Aucamp JP, Davies R, Hallet D, Weiss A, Titchener-Hooker NJ - Biotechnol. Bioeng. (2014)

The USD centrifugation mimic was used to predict clarification levels for centrifugation operations and compared to pilot scale results. A: Dewatering clarification studies of harvest broth from three fermentation processes compare well for pilot and USD scales. The feed streams were: Feed 9 USD (□) and pilot scale (▪), Feed 2 USD (◊) and pilot scale (♦) and Feed 8 USD (○) and pilot scale (●). B: Clarification studies of conditioned extract compare well for USD and pilot scales. The feed streams were Feed 2 USD (◊) and pilot scale (♦), Feed 9 USD (□) and pilot scale (▪), Feed 6 USD (▿) and pilot scale (▾) and Feed 8 USD (○) and pilot scale (●).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4282095&req=5

fig03: The USD centrifugation mimic was used to predict clarification levels for centrifugation operations and compared to pilot scale results. A: Dewatering clarification studies of harvest broth from three fermentation processes compare well for pilot and USD scales. The feed streams were: Feed 9 USD (□) and pilot scale (▪), Feed 2 USD (◊) and pilot scale (♦) and Feed 8 USD (○) and pilot scale (●). B: Clarification studies of conditioned extract compare well for USD and pilot scales. The feed streams were Feed 2 USD (◊) and pilot scale (♦), Feed 9 USD (□) and pilot scale (▪), Feed 6 USD (▿) and pilot scale (▾) and Feed 8 USD (○) and pilot scale (●).
Mentions: Pilot scale dewatering (Fig. 3A) and extract clarification (Fig. 3B) were performed for harvested material from several different feed streams and the USD clarification prediction studies conducted in parallel. For both centrifugation steps the USD predictions provided a good estimate of the actual clarification levels obtained in the pilot centrifuge. The USD dewatering level was fixed at 66.7% by removing supernatant equal to two-thirds of total volume before resuspension.

Bottom Line: The ability of cells to resist breakage was dependant on a combination of factors including host strain, vector, and fermentation strategy.The use of scale-down primary recovery process sequences can be used to screen a larger number of engineered strains.This can lead to closer integration with and better feedback between strain development, fermentation development, and primary recovery studies.

View Article: PubMed Central - PubMed

Affiliation: Bioprocess Research and Development, Novartis Phama AG, Basel, Switzerland. jean.aucamp@novartis.com.

Show MeSH
Related in: MedlinePlus