In 2020, the global cell culture market was valued at 3.4 billion USD, and between 2021-2025, it is poised to grow by 13 billion USD at a CAGR of 10.67%. The market growth is attributed to the increasing prevalence of cancer, autoimmune diseases, nephrological diseases and many more. As such, the need for increased research and development in cell culture therapy has never been so critical. Key players in the field hoping to make a difference include Biogen, Bristol Myers Squibb, Thermo Fisher Scientific Corporation, Merck, Fujifilm Irvine Scientific. Inc, Lonza, Axol Bioscience Ltd, to name a few.
To meet the growing market demands of cell culture therapeutics, the industry is turning its attention to prioritising the optimisation of Next Generation process development. Pharmaceutical leaders can save time and resources by streamlining development strategies via the selection and sequencing of process steps and achieve greater accuracy and quality of therapeutic cell products. The leading market drivers in such developments include process intensification and automation technologies. We look at some cutting-edge process strategies set to dramatically impact the cell culture development landscape in the immediate future.
Automation is one of the main priorities affecting the cell and gene industry today to expedite the next-generation development. Process improvements must be fast and utilise microscale robotic systems. By following established platforms consisting of common raw materials, parent cell lines, unit operations, and drug substance formulations, automated processes should deliver an intensified procedure for cell culture development. For Senior Scientist at Biogen, Jennifer Lin, the advantages of introducing automation into cell line development workflows is unquestionable.
Currently, Biogen is working on and dedicated to advancing their recombinant AV producer cell line platform, which relies heavily upon the implementation of robotics and AI. Lin explains how automation “not only decreases hands-on time but also increases throughput”. At Biogen, she points out that “by increasing the numbers of pools and clones that we screen and by bringing in a bunch of automation, we have successfully been able to increase the number of titers identifiable in selection streams”. Biogen’s ability to automate and use digital control during the process development stage enabled better understanding and optimisation of transfection efficiency and improved vector design. According to Lin, “improving these two aspects helped us increase titers by 15-fold”. Other popular means of automation within the field include data lakes, a software that simultaneously combines multiple outputs and translates them into analysable data.
2.) Process Intensification:
Process intensification refers to the improvements of a processing unit on an operational level. By implementing strategies to optimise and enhance therapeutic development, more economical and efficient operation of processes is enabled. Cell culture process intensification aims to increase viable cell density and volumetric and cell-specific productivity. Intensified processes help reduce the overall cost of goods and the use of raw materials. This is because less manufacturing footprint and time are required.
One current trend in process intensification includes the implementation of bioreactors to facilitate cell cultivation. A bioreactor is a vessel that conducts the biological reactions necessary for cellular and enzymatic immobilisation. Bioreactors play an integral role in ensuring the sterility of cell cultures. This process is particularly susceptible to biological contamination during transitions between sterile spaces. It is important to select the correct type of technology depending on biomanufacturing needs. The correct system must be specified and designed to provide long-term support. The different bioreactors available include a stainless-steel model, which holds a capacity of 10,000 to 20,000 litres, or a single-use bioreactor containing 1,000 to 2,000 litres. While stainless steel remains the preferred option for large-scale production, single-use bioreactors are popular for small-scale production.
3.) Scale Down Processing:
Scale down models are also fast becoming a popular approach to engineering the next generation cell cultures. Small-scale models support process development and can predict product quality. These function as incomplete representations of the more complex and extensive procedure of cell culture development. In particular, scale down processing works as a predictive evaluation system consisting of the qualitative assessment of time-course trends and extrapolation of operating conditions across multiple scales and equipment. The official FDA Process Validation Guidance states that “it is important to understand the degree to which models represent the commercial process, including any difference that might exist, as this may impact the relevance of information derived from the models”.
The main benefit of scale-down models and processing is that they are valuable for troubleshooting, enabling a more efficient and effective development process. Many companies are moving away from stainless steel tanks and towards disposable ones to allow flexibility to implement intensification processes. The industry is also adopting high-density cultures and implementing perfusion to reduce the number of inoculum steps to improve process development further. However, challenges in scale-down processing remain with the risk of variability between product titer lots.
As the cell and gene industry implements the next generation of cell culture process development, we at Oxford Global do not doubt its pioneering ability. The necessary and exciting innovations that are on the horizon will enable the efficient manufacturing of high-quality therapeutics. Such operational and technical advances will address clinical needs within the field and, importantly, seek to improve the patient experience.