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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Page 55 of 77

18 | SEPTEMBER 15, 2017 | and control strategy. Approximately 20 commercially approved biologics use perfusion manufacturing upstream; however, no cases of continuous downstream manufacturing processes have been reported for approved biologics. As such, there remains uncertainty in how regulators will approve a con- tinuous downstream manufacturing strategy. Also, although the FDA has established an Emerging Technol- ogy Team to help promote adoption of new technologies, CB experience needs to grow rapidly, and guidance on how to conduct QbD studies for CB are needed. Due to process complexity, develop- ing and running a continuous process requires a highly expert staff who can see trends and avoid potential impend- ing excursions, and transferring to the GMP manufacturing floor requires specialized operator training. Plans to manage failure modes are required to mitigate unplanned production stops and product losses. Also, QbD process development and validation work becomes more complex, because there are significantly more connected unit operations to control and validate. In addition, at the commercial stage, it is critical to ensure a consistent stream of high-quality raw materials are avail- able without interruption. Challenges with control strategy include those related to automation and process analytical technology (PAT). Real-time, in-line sensors and feedback/feedforward control are highly desired, but very limited in availability. This gap combined with the required consumption of large volumes of cell-culture media, buf- fers, and other raw materials poses a significant business risk to biomanu- facturers considering end-to-end con- tinuous processing. Having a control strategy in place with the right auto- mation is imperative to successfully run continuous operations, especially in a GMP commercial manufacturing environment. Solutions that Support Continuous Bioprocessing The benefits of CB outweigh the risks in some situations, but it may not be practical for all bioprocesses. We recommend conducting a needs- based analysis of your process with help from experts in GMP continu- ous manufacturing. Such an analy- sis can highlight situations where Continuous Bioprocessing: Is It for Everyone? Continued from page 17 CO N T I N U O U S B I O P R O C E S S I N G Table 2. Category Topic / Issue Batch Fed-batch Concentrated fed-batch Continuous perfusion (cell recycle only) Continuous perfusion (cell + product recycle) Economic Capital cost, utilization Economic Cell culture medium consumption Economic Cumulative QC business risk Economic/ Operational Process and validation complexity, training, skills Operational Process development and quality by design regulatory/ time/cost Operational Manufacturing scale-up risk Technical Product quality/ consistency (if product is unstable in batch or fed batch) Technical Product titer Technical Cell harvest difficulty/DNA and HCP contaminants Technical Impact on downstream purification difficulty Upstream Bioprocessing: Breakdown of Relative Risks and Benefits for Five Manufacturing Approaches Risks and benefits are shown in a heat map based on the authors' continuous bioprocessing experience (bright red: relative higher risk; bright green: greatest benefit). We encourage readers to perform their own assessments and to use the risk-benefit tables in this paper as a general guide. It is important to consider that the benefits could vary between different application areas (for instance, monoclonal antibodies, vaccines, recombinant proteins, and plasma). Parrish Galliher is chief technology officer, upstream; Guenter Jagschies, Ph.D., serves as strategic customer relations leader, bioprocess; and Amit R. Dua is global marketing strategy leader, bioprocess, GE Healthcare Life Sciences. Website:

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