We are at an interesting pivot point in bioprocessing where there is a keen interest in the intensification of BioPharm manufacturing. Improving flexibility, minimizing risk and reducing cost are the key drivers. In this talk, we use advanced whole bioprocess models to understand the drivers and impact of these different modalities.

The presentation will address central challenges in digitalization and big data analytics in biopharma and will demonstrate the potential to provide systematically value through integration of smart digital technologies into the work stream. The presentation will be based on several industrial use cases in USP and DSP showing benefits from software-assisted and -enabled process monitoring, control, optimization and automation.

In an integrated continuous biomanufacturing process, the unit operations are interlinked. The exit mass flow is the inflow of the following one. The process disturbances are propagating throughout the entire process. RTD based models are the fundamentals to control such complex processes. The effect of surge tanks and periodic quasi-continuous operations will be demonstrated.

A tool for process intensification through multistep integration.
Brief overview of control strategy and case study results.

For the first time to our knowledge, the implementation of a continuous protein A capture process for antibody applications (CoPACaPAnA) embedded in an end-to-end single-use GMP manufacturing process of a multispecific mAb using the Cadence™ BioSMB 350 system was conducted. Moving to a more heterogeneous portfolio of antibodies and fusion proteins, more flexibility and lower expenditure is desired. We demonstrated that employing single-use equipment and continuous processing can be highly beneficial.

Novel therapeutic modalities, such as virus-based biologics or exosomes are hailed as potential game-changers for healthcare. The present talk will focus on the challenges faced during the development of continuous purification strategies. Case studies figuring the purification of gene therapy vectors, oncolytic viruses and exomes will be highlighted.

Continuous manufacturing (CM) introduces the benefits of cost efficiency, reliability and scalability for the manufacturing of biopharmaceuticals. In combination with disposable equipment closed processing is feasible. Bayer’s unique CM platform consists of a series of downstream processing (DSP) unit operations through which the drug substance moves continuously, where critical process parameters are monitored and controlled in real-time. Reduced manual interference will also lead to reduction of operator errors and according deviations. The presentation also illustrates comparability of CM versus batch processing in a side-by-side approach covering process information, real-time analysis as well as quality data from intermediates and final drug substance.

Continuous viral inactivation remains a challenge while the biopharma industry moves towards continuous integrated processing. However, in the past few years, different approaches were developed in order to achieve the minimum incubation in continuous mode – the biggest challenge. One such approach is the packed bed reactor, which guarantees a narrow residence time distribution. A case study will be presented and continuous inactivation by low pH and by solvent/detergent will be demonstrated.

This presentation will describe the steps taken by a UK-based consortium of biopharmaceutical manufacturers to develop a fully automated and integrated continuous downstream platform. The overarching process control strategy allows a single operator to start up, run and shut down an entire downstream process consisting of up to nine unit operations from capture chromatography through to final formulation.

Whereas batch and fed-batch processes are common for the production of therapeutics, perfusion is a rediscovered trend in biotechnology. With Glycotope’s decade-long expertise in perfusion cultivation, we share obstacles and difficulties for these processes from an R&D point of view and provide a head-to-head comparison of a CHO-fed-batch to a GEX® (Glycotope’s proprietary human cell line) perfusion process for a difficult to express protein.

The most common tool used for purification of antibodies is protein A affinity chromatography, a method that offers high productivity and pure protein product. However, elution of captured antibodies requires low pH and that might be deleterious. We have addressed this issue by developing a protein domain displaying calcium-dependent binding to IgG. To evaluate the domain in affinity chromatography, a matrix based on a tetrameric version of this domain was produced. From this column, elution in physiological pH was possible and IgG recovery was shown to be comparable to commercial matrices.

This presentation will focus on the development of high-affinity, highly-specific diagnostic and therapeutic binding molecules based on the creation of two novel phage displayed libraries of a uniquely stable and hydrophilic protein scaffold. This novel scaffold has molecular properties designed to achieve significant impact as a new generation of powerful tools in areas of clinical need, both as diagnostic and therapeutic entities. Processing of specific candidates will be described.