Genetic Engineering & Biotechnology News

AUG 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Page 24 of 33 | Genetic Engineering & Biotechnology News | AUGUST 2018 | 23 retained at least 75% of the initial fed–batch titer. Collectively, these studies demonstrate that the CHOZN GS platform is a robust solution for obtaining high titers and stable recombinant protein expression. Optimizing Cell Culture Media and Feed Strategy For this turnkey solution, growth and production metrics can be improved using matched cell culture media and by varying feed amounts and timing. Our platform uti- lizes EX-CELL ® Advanced cell culture media and feeds. In the example shown in Figure 2, a CHOZN GS recombinant cell line was subjected to feed optimization by varying feed amounts and timing as indicated. Compared to the control, one of the EX- CELL Advanced feed regimens improved ti- ters 30%. When these or similar strategies are used, improvements can be expected with CHOZN GS recombinant cell lines. Scale-Up The performance of a recombinant cell line at large scale is a key parameter for upstream success. To ensure that performance metrics such as titer and quality are met, an under- standing of small-scale models and scaling parameters for a particular system is needed. We've built a complete portfolio of scalable, single-use bioreactors based on these factors to improve the speed to upstream success. The small-scale Mobius ® 3L single-use bioreactor contains three probe ports, all the connections needed for both gas and feed additions, and a sampling port. The system comes presterilized and ready to connect to a variety of controllers. The pilot-scale Mobius 50- and 200-L bioreactors contain stainless steel bases and integrated controllers. A presterilized single- use bioreactor bag needs to be installed into the stainless-steel carrier with a SensorReady loop prior to running the system. All of the connections are made using our Lynx S2S single-use sterile connector. Our production-scale Mobius 1000- and 2000-L bioreactors have the same features as our 50- and 200-L systems, with the added benefit of a vessel drawer, allowing the easy in- stallation and removal of single-use assemblies. Keeping the importance of speed in mind, we set out to scale-up from a shake flask to the 50-L scale (Figure 3A). Duplicate shake flasks were run in parallel with the feed strat- egy optimized in small scale. Three duplicate runs of the 3-L system were performed with the agitation at 20 Watt/m 3 , the pH at 6.9, the dissolved oxygen (DO) at 30%, and the temperature 36.8 °C. In the first run, we learned which sparg- ing strategies worked best for these cells and determined the power setting. In the second run, we determined how to manage the pH set point of the bioreactor. In the third run, we scaled up to the 50-L system. In addition to speed and matching product titers, matched product quality is paramount for upstream success. Our platform was de- signed with product quality in mind. In the ex- periment above, antibodies were collected at harvest and the glycan species were identified. The percentages of the four major glycans (G0 in dark blue, G1F in turquoise, G2F in pur- ple, and high-mannose in blue-green) for each of the scales are shown in Figure 3B. Across the scales, the percentages are highly similar. These results show that the CHOZN GS cell line is scalable for titer and product qual- ity at 3-L and 50-L scale with limited optimi- zation, resources, and time. In conclusion, the speed of cell line and process development is a key driver in biologic production. We presented a turnkey solution that was built with speed in mind. The plat- form not only provides high titer, but also pro- vides a path to scalable critical quality attri- butes. This solution provides users confidence of upstream development success. BioLector ® Pro Microbioreactor Develop your BioProcess in a couple of days! EUROPE i n f o @ m 2 p - l a b s . c o m P h o n e + 4 9 - 2 4 0 1- 8 0 5 - 3 3 0 USA i n f o U S @ m 2 p - l a b s . c o m P h o n e + 1 - 6 3 1 - 5 0 1 - 1 8 7 8 2015.07 | vierviertel · Process development · Fed-batch optimization · Media screening · pH profiling · Induction profiling The Microbioreactor Company 32 Microbioreactors + pH Control + Feeding = Full Bioprocess Control MATH CAN BE SO EASY Bioprocessing Figure 3. Scalability of a CHOZN® recombinant cell line in Mobius bioreactors. (A) At all the scales evaluated—shake flask (SF), 3 L, and 50 L— the titer results in the bioreactors were similar and peaked around 2.3 g/L. (B) Glycan analysis identified and quantified the major glycan species.

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