Genetic Engineering & Biotechnology News

MAY15 2017

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Genetic Engineering & Biotechnology News | GENengnews.com | MAY 15, 2017 | 23 make matters even worse, manufacturers have their own preferred procedures, expression hosts, media, and purification strategies. For an unbiased head-to-head comparison of both technologies, we employed cutting-edge pro- cess simulation software to calculate the cost of goods based on Esetec and a CHO cell culture. The analysis for a hypothetical nonglyco- sylated protein, assuming identical secretion titers of 2.2 g/L, was performed with BioSolve Process 7 (Biopharm Services). As far as pos- sible, identical input cost data were used for CHO and Esetec. Since both technologies se- crete the active protein into the culture broth, primary downstream processing (pDSP) and downstream processing (DSP) are widely comparable (Figure 2A). Therefore, the simu- lation is based on a similar pDSP/DSP se- quence with the exception of the mammalian- specific viral inactivation/filtration steps. The purification setup contains three chromatography columns with identical yields and life cycles. The calculations are based on three working shifts and stain- less steel fermenters. The estimated over- all costs for facility investments, capital costs and labor were identical. Initially, total manufacturing costs of a single batch with 1,200 L working volume (w/V), cor- responding to 1,500 L total fermenter vol- ume, were analyzed. Processing of a mammalian batch takes almost three times longer than Esetec, driven by the extensive fermentation times of CHO cells. The fast-growing Esetec host is clearly superior and reduces the batch du- ration by 65% (Figure 2B). Cost drivers for GMP manufacturing are capital and labor costs; both are drastically reduced with the faster Esetec batch. Together with viral inactivation/filtration and more cost-efficient media, a single batch of the conventional CHO process is 2.7-times more expensive (Figure 2C). The simulated annual output of the aforementioned facility, equipped with a single fermenter, reaches up to 75 batches per year for Esetec, compared to just 21 CHO batches (Figure 3A). As pro- duction of several consecutive batches allows staggering, which is common for commercial manufacturing, we further assessed the rela- tive cost of goods for the production of 50 kg bulk drug substance using a 6,000 L facility with 4,800 L w/V (Figure 3B). The short fermentation of the Esetec pro- cess reduces the production time 3.3-fold, which equates to savings of ~64% compared to the cost of using CHO cells (Figure 3B). To overcome the slow growth of mammalian systems in commercial operations, parallel CHO fermenters are used, which feed one DSP line to achieve 100% utilization. Even compared to such an optimized CHO plant that is equipped with four identical fermenters, Esetec is faster and ~37% cheaper (Figure 3B, shaded bar), highlighting its tremendous advantage and high productivity. Conclusion Wacker Biotech's microbial secretion technology Esetec offers a cost- and time- efficient alternative for the production of any nonglycosylated therapeutic protein. With straightforward strain and process develop- ment, Esetec combines all benefits of micro- bial and mammalian systems. In a process simulation, assuming similar titers/yields, CHO manufacturing on a 1,500 L GMP-scale proved to be 2.7-times more expensive than Esetec. The advantage is mainly driven by shorter fermentation times and obsolete viral depletion steps. The overall superior productivity, shorter development times and lower cost of goods distinguish Esetec as a novel, cost-efficient production system, ideally suited for manufacturing nonglycosylated biopharmaceuticals. Bioprocessing Hagen Richter, Ph.D., is a trainee at Wacker Chemie, and Ilona Koebsch, Ph.D. (ilona.koebsch@wacker.com), is business development manager at Wacker Biotech. Web: www.wacker.com/biologics. Tutorial Leading the Data Enabled World The first peer-reviewed journal to connect a world where the pace from research to implementation is ever accelerating The go-to platform for: ® Advances in new big data technologies ® Discussion of unique and innovative big data ideas ® Problems, challenges, and security issues in managing big data ® Sharing and dissemination of world-class data science expertise www.liebertpub.com/big Figure 3. Annual production capacity and relative cost-of-goods based on the simulated Esetec and CHO processes. (A) Total number of GMP batches per year based on the simulated batch times (Figure 2) and three working shifts. The corresponding production quantity is calculated for 1,200 L w/V (1,500 L total volume) fermentation with primary titers of 2.2 g/L. (B) Relative costs to manufacture 50 kg bulk API with 4,800 L w/V (6,000 L total volume). A facility with a single CHO fermenter is up to 2.8 times more expensive than Esetec. Even four parallel CHO fermenters feeding one DSP unit (fully utilized) result in 1.6-fold higher cost of goods compared to a single Esetec fermenter. A B Figure 2. Process simulation results for fermentations with Esetec and CHO cells in 1,200 L (w/V). (A) Simulated manufacturing process for Esetec and CHO cell culture using BioSolve Process 7 (Biopharm Services). Steps displayed in light grey only apply for CHO cell. (B) Total process times of a single Esetec and CHO GMP batch based on a three-shift model. Due to short fermentation times, Esetec reduces the process duration by up to 65%. (C) Total costs of single GMP batches relative to Esetec. The cost of goods is reduced up to 2.7-fold due to shorter process times, reduced media costs, and viral depletion steps. A B C

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