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 21 of 33

20 | AUGUST 2018 | Genetic Engineering & Biotechnology News | the final product, without screening." Another advantage of the approach is cost reduction. "Our analysis," says Dr. Hung, "suggests that the approach saves us around $200,000 per production run, based on shorter running times and lower labor costs." Computational Fluid Dynamics A computational approach can also be used to optimize upstream processes during scale-up, says Michelle LaFond, senior direc- tor, bioreactor scaleup and development, Re- generon Pharmaceuticals. LaFond uses com- putational fluid dynamics (CFD) to identify laboratory-scale culture parameters that will be hardest to replicate at manufacturing scale. These are known as scale-dependent parameters. Current approaches to identifying scale- dependent parameters—which are based on correlations for power per unit volume (P/V) and stripping gases—assume that the production bioreactor will simply be a big- ger version of the laboratory bioreactor. Al- though these approaches are effective when laboratory and production bioreactors are like-for-like in terms of impeller and sparger geometries, they are insufficient when biore- actor geometries differ. The inability to identify scale-dependent parameters, warns LaFond, results in tinker- ing during scale-up, leading to lengthy and therefore costly technology transfer. "CFD, in contrast, allows us to leverage thermodynamic principles and develop a more comprehensive, high-resolution under- standing of the fluid properties within a bio- reactor," she explains. "It also leads to faster data generation and decision making due to minimized reliance on empirical data. "By implementing CFD, the impact of different bioreactor designs is mitigated. CFD also allows us to simulate conditions in the bioreactors for various agitation rates and generate a library of engineering parameters such as P/V, energy dissipation rate, mixing times, and shear. While some of this can be done empirically, the simu- lations help us to cover more ground and obtain more granular data by modeling lo- calized fluid properties rather than just the mean response that you get from bioreactor experiments." LaFond and her colleagues use the data to make predictive scale-down bioreactor models to determine optimal operating con- ditions at the pilot scale in accordance with quality-by-design principles. "The key benefit is a seamless transfer to manufacturing, obviating the need for pro- cess modifications or investigations at scale," LaFond declares. "This is a direct result of the data-driven process transfers to com- mercial scale, with more of the effort and resources being spent in characterizing the process during development." Disposable Technology As bioprocess development progresses from stage to stage, it may switch from one bioreactor system to another, so that at each stage, the most suitable bioreactor system is used. This kind of flexibility is becoming more common as the number of specialist technologies grows. For example, while Bristol-Myers Squibb primarily uses large-scale bioreactors for commercial manufacturing, the company conducts some of its early process develop- ment, specifically clone selection, in dispos- able systems. The idea is to use the most effective tech- nology for each unit operation, comments Ping Xu, Ph.D., a senior scientist in Bristol- Myers Squibb's biologics development and supply division. According to Dr. Xu, the company uses Sartorius Stedim Biotech's ambr 250 system for clone selection and ear- ly-stage biologics process development. "The instrument has been integrated into our platform working flow to select the lead clone from 6 or 12 research cell bank clones," he says. "After the lead clone is se- lected, the ambr 250 system allows us to op- timize the process. In the past, we used shake flasks and 5-L bioreactors in parallel for screening clones and process development." The advantages are manifold, asserts Dr. Xu, who points out that one employee using the disposable technology can achieve in a day what a team of three employees using the firm's previous approach would have ac- complished only after several days. The ambr 250's advantage with respect to time savings is due to the system's fast turnaround, asserts Dr. Xu, who adds that this advantage is especially important to sci- entists "facing tight timelines for achieving first-in-human applications for new biologic molecules." "The consumables for the ambr 250 are slightly costlier than those for 5-L bioreac- tors," Dr. Xu notes. "But the ambr 250 also reduces labor costs, so it is still valuable in process development." All of the bioprocessors interviewed for this article will be speakers at Cambridge Healthech's Bioprocessing Summit, which will be held from August 13–17 in Boston. Bioreactors Continued from page 18 Bioprocessing The only peer-reviewed journal focused on the rapidly moving fi eld of 3D printing and related technologies Editor-in-Chief: Skylar Tibbits Sign up for TOC Alerts

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