Online real-time measurement of the mAB product concentration can significantly accelerate the combined cell culture harvest, filtration, and protein A (pA) capture step. A UPLC pA column quantification method that provides mAB concentration updates as rapidly as every 1.5 minutes was developed and qualified. This can accurately monitor the rapidly changing mAB concentration and allow for the product to be continuously captured, eliminating the need to pool the entire harvest and measure concentration offline before loading. Efficient next-generation processes also have increased pA load times, which minimize pA resin usage but can put product quality at risk. To mitigate, we developed an online UPLC reverse phase method capable of measuring clipping of interchain disulfide bonds. These two methods can be run in parallel on one UPLC, and case studies demonstrating utility of these PAT methods during the pA mAB capture process will be presented.

Optimization of protein production often results in bioprocesses operating under suboptimal conditions and hence in extended cycle times, excessive raw material and utility requirements, and elevated numbers of process or product failures, which together culminate in a high cost of manufacturing. To ensure consistent drug quality and reduce batch-to-batch variability, pharmaceutical companies and regulatory authorities aim to replace the “quality-by-testing” with a “quality-by-design” strategy. Learn more about quality-by-design in this webinar.

The emergence of high-throughput technologies challenges the interpretation of large datasets. One way to identify meaningful outcomes impacting process and product attributes from large datasets is using systems biology tools. While pharmaceutical companies are already investing substantially in computational approaches to guide drug discovery and cell design, model-based methods can also be applied for upstream process development to improve process understanding, lower the experimental effort, and increase the process robustness.

Manufacturing strategies for biologics over the drug product development and lifecycle need to be flexible to accommodate current-day realities. From the manufacturers and the patient’s perspective, it is becoming increasingly critical that the new drug products reach the market sooner, and therefore, compressed
timelines are being assigned to drug product manufacturing process development. The focus of this presentation will be on some of the key technical considerations to facilitate efficient drug product manufacturing process development for biologics, including monoclonal antibodies.

Cell culture processes are currently developed in an explorative way, using DoE approaches. However, lots of knowledge is available, which can be captured in digital twins. This contribution will show how digital twins can be used for targeted design of experiments to achieve optimum VCC, productivity, and product quality. This concerns the predictive setting of pH and temperature shifts, as well as optimizing the feed trajectory. This will allow quicker bioprocess development and more optimized design results, which can be used further for validation purposes.

The aim of process development and characterization is to define a control strategy that leads to meeting product specifications at the lowest possible batch-failure rates. However, modelling of processes consisting of multiple unit operations across the product lifecycle is a complex task. Here, integrated process models will be introduced, which are digital twins of the production process, and herein convenient tools for leveraging data by turning it to process knowledge and control strategies.

Autonomous high-throughput cultivation and sample analysis in fully automated robots are a key for shorter product development cycles in the biopharmaceutical industry. Our automated robotic platform integrates parallel minibioreactors and analytical instruments, as well as at-line data evaluation and parameter adjustment. Thus, running experiments can be automatically influenced so that the parameter space of the used mechanistic or hybrid models is accurately described. Application examples include clone selection, process optimization and robustness analysis, scale-up and process control.

The need to bring new biopharmaceutical products to market more quickly and to reduce final manufacturing costs is driving early-stage, small-scale bioprocess development. This presentation will demonstrate the scale translation of a fedbatch process with a GS-CHO cell line producing a monoclonal antibody from a single-use 24-well parallel miniature bioreactor to a 5 L stirred tank reactor, showing good prediction of cell culture performance.

Apoptosis is a form of programmed and controlled cell death that accounts for the majority of cellular death in bioprocesses. Cell death affects culture longevity and product quality; it is instigated by several stresses experienced by the cells within a bioreactor. Understanding the factors that cause apoptosis as well as developing strategies that can protect cells is crucial for robust bioprocess development. In conclusion, understanding apoptosis is important in quality-by-design bioprocess development from clone screening to production.