Scaling Down of Biopharmaceutical Unit Operations — Part 1: Fermentation - The fermentation process can be challenging to scale down and several factors must be evaluated for each step. - BioPha

ADVERTISEMENT

Scaling Down of Biopharmaceutical Unit Operations — Part 1: Fermentation
The fermentation process can be challenging to scale down and several factors must be evaluated for each step.


BioPharm International



Figure 3. Comparison of Dissolved Oxygen Profiles in Small- and Large-scale Fermentations
Figures 2 and 3 illustrate a successful scale-down of a microbial fermentation process based on culture growth and dissolved oxygen profiles, respectively. While the dissolved oxygen profiles in Figure 3 were slightly different, the rates of oxygen consumption (excluding the fluctuation at t=20 hours) were similar.

SUMMARY Creation of scale-down models that meet qualification requirements can be challenging, particularly for upstream unit operations. These models can be of great use when performing experimental studies in an efficient and economical fashion. However, there are considerations unique to each unit operation that apply during scale-down. It must be mentioned that while scale-down studies certainly increase the chances of having a successful validation campaign, they only provide guidance. The actual confirmation must be made at large-scale.

Anurag Rathore, is a principal scientist at Amgen Inc., 30W-2-A, One Amgen Center Drive, Thousand Oaks, CA 91320, 805.447.4491, fax 805.499.5008,
Raj Krishnan work for Amgen Inc, Thousand Oaks, CA. Stephanie Tozer work for Amgen Inc, Thousand Oaks, CA. Dave Smiley work for Amgen Inc., Longmont, CO. Steve Rausch work for Amgen Inc., Longmont, CO. Jim Seely work for Amgen Inc., Longmont, CO.

REFERENCES 1. Dahlgren ME, Powell AL, Greasham RL, and George HA. Development of scale-down technique for investigation of recombinant Escherichia coli fermentations: Acid metabolites in shake flasks and stirred bioreactors, Biotechnol. Prog.1993; 9:580-586.

2. Reynolds T, Boychyn M, Sanderson T, Bulmer M, More J, and Hoare M. Scale-down of continuous filtration for rapid bioprocess design: Recovery and dewatering of protein precipitate suspensions, Biotech. Bioeng. 2003; 83:454-464.

3. Varga EG, Titchener-Hooker NJ, and Dunhill P. Prediction of the pilot-scale recovery of a recombinant yeast enzyme using integrated models, Biotechnol. Bioeng. 2001; 74:97-107.

4. Godavarti R, Petrone J, Robinson J, Wright R, and Kelley BD. Scale-down models for purification processes: Approaches and applications, in process validation in manufacturing of biopharmaceuticals, eds. Rathore AS and Sofer G. Marcel Dekker, New York 2005.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

Pandemic Vaccine Facility Dedicated in Texas
September 19, 2014
GSK Fined in China Bribery Scandal
September 19, 2014
Guideline Delineates How to Implement GS1 Standards to Support DSCSA
September 19, 2014
GPhA Supports Restricted Access Bill
September 18, 2014
Baxter Initiates Voluntary Recall of Potassium Chloride Injection
September 17, 2014
Author Guidelines
Source: BioPharm International,
Click here