Genetic Engineering & Biotechnology News

SEP15 2017

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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GENengnews.com | SEPTEMBER 15, 2017 | 21 quickly with low production costs. It avoids the need to build large stain- less-steel facilities or outsource their production capability to a third party. Exploring Process Intensification The advent of single-use technol- ogy has allowed firms to build new production plants much more quickly than was possible than former set-ups, which featured stainless-steel plants and were associated with a lower up- front cost. The technology is reaching a level of maturity such that engineers are increasingly considering it for commercial manufacturing facilities. However, an analysis performed by the industry investigating the costs associated with running single-use facilities (in which fed-batch processes are operated and generate titers of 3 g/L from six 2,000-L bioreactors), has shown that the output of these facili- ties is limited to around 500 kg/y. If market demand exceeds this figure, more investment is required to build additional production lines. When operated to produce over 500 kg of product per year, this can lead to much higher net present cost. Fully continuous processes are likely to pro- vide the most consistent product qual- ity and the lowest footprint overall. However, several challenges related to implementing these technologies remain. These include assuring robust process-control strategies across the entire production chain and defining appropriate regulatory pathways for product approval. While fully continu- ous bioprocesses show great promise, the benefits will most likely be realized in the medium- to long-term. This is why we at Sartorius Stedim Biotech (SSB) believe that, particularly in the short-term, process-intensifica- tion projects can add immediate value to our customers' operations while still providing lower cost of goods and great flexibility. Scalable technologies for process intensification are available now. The industry analysis shows that companies can reach productivities of 1,500 kg of product per year simply by intensifying steps in the produc- tion process and without needing sig- nificant additional investments over a single-use fed-batch facility. Single-use process intensification serves as a compromise to end-to-end solutions; it allows manufacturing agility, keeps cost of goods low, and improves product quality. The ap- proach is particularly useful in multi- product facilities, when rapid change- overs between products are required. Upstream Processes Upstream processes can be intensi- fied by using N-1 perfusion steps that allow production bioreactors to be seeded at a higher viable cell density. Doing so increases culture productiv- ity, especially during what would nor- mally be the growth phase of a stan- dard fed-batch process. The integral of viable cells, a proxy measurement for product titer, can be increased still further by implementing concentrated fed-batch processing using a continu- ous culture feeding strategy coupled with a cell-retention device. Extremely high cell densities can be achieved be- cause depleted nutrients are replaced and spent media removed. The optimized scheduling of con- centrated fed-batch cultures can allow production managers to gain produc- tivity improvements so significant that they need not invest in a fully continu- ous production scenario. Downstream process scientists can intensify the purification of harvests from such cell cultures us- ing multicolumn chromatography techniques. Companies can drive this still higher by replacing conventional chromatography resins with single-use membrane-adsorber technology. Prod- uct binding to membrane adsorbers is not diffusion-rate-limited because mass transfer of the product to the membrane is dominated by convective flows (Figure 2). Sanofi has showed that CO N T I N U O U S B I O P R O C E S S I N G ➜ Gerben Zijlstra is platform marketing manager, continuous biomanufactur- ing, integrated solutions marketing, and Priyanka Gupta is global senior bioprocess modeling consultant, inte- grated solutions marketing, at Sartorius Stedim Biotech (www.sartorius.com). Figure 2. SSB's newly developed Sartobind cassette system is a unique single-use solution enabling large-scale bind-and-elute membrane chromatography that has the potential to replace conventional chromatography resins.

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