Tuesday, September 24, 2024 - Day One of Main ConferenceTuesday, 24 September 2024 - ET (Eastern Time, GMT-05:00)

Considerations when designing a scale up strategy; Tools for scale up calculation and facility fit assessment; Case studies.

This presentation will cover the strategy for clone and process platform selection for a therapeutic fusion protein. The selection process involves generating clonal cell lines, assessing the cell culture process performance, and evaluating product quality attributes in automated microbioreactors. Perspectives from product development, analytical product quality comparability, cost of good reduction, and strategies for further process development will be discussed.

This presentation explores MacroGenics successful application and scale-up of Thermo Fisher's Efficient-Pro™ medium/feed in the development and manufacturing of monoclonal antibodies (mAbs). By transitioning from a standard platform to Efficient-Pro™, significant improvements in titer and comparable aggregation levels in CHO type 2 cells were achieved. The study highlights the process development, scale-up from lab to 500L single-use bioreactors, and the subsequent transfer to GMP scale. Key findings demonstrate Efficient-Pro™'s performance, making it an optimal choice for companies aiming to enhance productivity and efficiency in mAb production. Attendees will gain insights into the practical challenges and solutions encountered during the process, as well as the collaborative efforts between MacroGenics and Thermo Fisher that led to this success.

Scale-down models play a crucial role in process development, characterization, and optimization for cell culture processes. In addition to matching the at-scale manufacturing performance, an effective scale-down model should also be predictive of changes to various scale-dependent and scale independent parameters. One of the key methodologies to develop a good scale down model for cell culture processes is through the maintenance of oxygen mass transfer and CO2 removal through agitation and gassing strategies. In this case study, we present a scenario where the initially developed scale-down model exhibited comparable product-quality attributes to the manufacturing scale but showed lower growth and productivity characteristics. Further investigation revealed that the poor growth and productivity was linked to the CO2 buffering capacity of the media which became more pronounced at the smaller scale. To address this issue, we systematically evaluated various gassing strategies, including sparging and overlay, with the aim of optimizing conditions to align more closely with the growth and productivity patterns observed at the manufacturing scale. The efforts resulted in an optimized scale-down model that now better mimics the growth and productivity trends seen in the manufacturing scale. This enhanced model is instrumental in improving the predictability and reliability of the at-scale manufacturing process.

Antibody drug conjugate therapeutics are an increasingly common modality due to their targeted ability to deliver various cytotoxic or immune-modulating payloads to specific cell types or tissues. This presentation covers a case study navigating the added complexity of selecting an appropriate mAb binder, payload, conjugation method, and drug-antibody ratio with emphasis on opportunities and challenges to accelerate pre-clinical development and IND filing.

The demand for producing therapeutic recombinant proteins is generating a renewed interest in perfusion cell culture technologies, leading to the development of cell culture media that can support high cell densities (HCD). However, HCD in bioreactors can generate challenges, due to the requirement to maintain highly productive cells over long periods of time. Implementing a perfusion process utilizing a production bioreactor is costly, requiring small scale models to optimize the process. In this study, BalanCD CHO Perfusion and Perfusion Media Survey Panel was evaluated with perfusion mimic models and a table-top perfusion capable bioreactor featuring an alternating tangential flow filtration unit in both a N-1 perfusion process and a recombinant antibody production process. We demonstrate the optimization of a perfusion process in a table-top perfusion capable bioreactor, scaling-up from small scale perfusion mimic models. We assayed peak cell densities in an N-1 perfusion process demonstrating how productivity is related to various metabolites, glucose, and aeration during a continuous steady-state culture. Our results demonstrate success of achieving high productivities in a continuous steady-state perfusion culture through the optimization of bioreactor parameters, while utilizing an appropriate cell culture medium, without achieving peak cell densities.

Learning Objectives:

- The use of perfusion mimic models to assess a perfusion medium

- Scaling from a micro bioreactor to a table-top perfusion capable bioreactor

- Optimization of the perfusion process to achieve increased productivity

• Grab a 'Cloud Spritz' (Aperol Spritz)
  • Culture Bioscience's booth (328)
• Grab a SmartLabs 75 (French 75)
  • SmartLabs Booth (1824)