An Economic Comparison of Three Cell Culture Techniques - Comparing the economic feasibility of a typical glycosylated protein. - BioPharm International


An Economic Comparison of Three Cell Culture Techniques
Comparing the economic feasibility of a typical glycosylated protein.

BioPharm International
Volume 24, Issue 2, pp. 54-60


This article has provided an economic comparison for the production of a typical glycosylated protein using the FB, CFB, and CBP technologies. The CFB and CP processes are based on the ATF System. The model results revealed that in the base case, CoG savings of 25% and 45% can be achieved using the CFB (1000 L, 17 g/L) and CP (1000 L, 0.8 g/L) technologies, respectively, when compared with the FB process (10,000 L, 2 g/L). The bulk of the savings is derived from the reduction in capital requirements due to higher productivities, resulting in reduced overall bioreactor capacity in these processes. The use of the CFB and CP technologies would seem a potential approach toward lower upfront capital investment and operating costs. Sensitivity analyses were performed on the product titer in the CFB process and the bioreactor volume in the CP process. The feasibility of the CFB technology reduces at the worst-case product titer (10 g/L) reported in current industrial processes. The CP CoG is still lower than the FB CoG when the bioreactor volume is reduced to 500 L.

In addition to cost considerations, there are other key factors that may affect the selection of an appropriate process for a drug candidate. The existing fed-batch and perfusion processes are well-known but both have limitations. The CFB mode with the ATF System is recommended if the product of interest is a single concentrated product stream harvested from the reactor. The CP mode can be used to reduce the size of bioreactor required to produce the same amount of product as in fed-batch or perfusion.

This article has not evaluated the use of the ATF System during the cell banking and seed expansion stages in the upstream manufacturing process.6 Performing perfusion cultures with such a system can generate large cell mass for high density freezing to be used for cell-banks preparation. High cell density freezing reduces the inoculum expansion time by removing the first seed passages and inoculates a small bioreactor directly from the freezer. This leads to reduced manual handling of culture and improved facility use.

The impact of the use of disposable bioreactors in the cell-culture operations has not been captured in this article analysis. Disposable systems are easier to set up and they eliminate cleaning requirements; hence the turnaround time for such single-use technologies is typically shorter compared with their stainless-steel counterparts. The faster turnaround time could result in increased plant throughput and affect the production costs of the facility.

Janice Lim is a bioprocess consultant and Andrew Sinclair is managing director, both at Biopharm Services, Chesham, UK. Jerry Shevitz is president and John Bonham Carter is vice-president of sales and business development, both at Refine Technology, Pine Brook, NJ, 793.993.3003,


1. Chu L, Robinson DK. Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol. 2001;12:180–187.

2. Carstens, Jason. Perfusion! Jeopardy or the Ultimate Advantage? BioProcess International webinar. 2009 Sept.

3. Furey J. Scale-up of a cell culture perfusion process. Gen Eng News. 2002;22:62.

4. Mora J, Sinclair A, Delmdahl N, Gottschalk U. Disposable membrane chromatography performance analysis and economic cost model. Bioprocess Int Suppl. 2006:4:38–43.

5. Lim JAC, Sinclair A, Kim DS, Gottschalk U. Economic benefits of single-use membrane chromatography in polishing—A cost of goods model. Bioprocess Int. 2007;5(2)48–56.

6. Noe W. Paradigm changes and technology gaps in the biopharmaceutical industry. BioProcess International Conference & Exhibition; 2009 October 12–15; Raleigh, NC, USA.

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