Genmab’s DuoBody platform is a versatile technology for generating bispecific antibodies via a post-production exchange process. The HexaBody platform allows for the creation of potent therapeutics by promoting hexamer formation on the cell surface for enhanced complement-mediated cytotoxicity. These platforms are used to create next-generation antibody therapeutics. Case studies describe the downstream processing strategies that are utilized to control the process at research and manufacturing scale.

Developing commercial Upstream and Downstream processes for potent molecules can be highly challenging due to processes requiring containment facilities to isolate the product from the operator. Standard high-throughput screening platforms are not viable due to the limited space within these highly controlled containment facilities. This project aimed to configure and program an AKTA Pure to establish an automated method to process multiple bioreactor samples through multiple purifications and buffer conditioning steps in containment to enable better decision-making for Upstream development.

An industry-wide team consisting of 18 companies from pharmaceutical manufacturers and suppliers organised by BioPhorum is working on a proof of concept for controlling product collection during bind-and-elute cation exchange chromatography of monoclonal antibodies. The analytical technique of choice is real-time multi-angle light scattering (RT-MALS) which is used for aggregate monitoring. This talk will summarize the project setup, the challenges encountered and the experimental design developed by the team. Initial results from experiments performed will be also highlighted.

Ultra- and diafiltration is a critical step in virtually every bioprocess. Due to various membrane interactions, it can be difficult to fully recover the product which leads to low yields and higher overall process costs. By introducing controlled process variations, hybrid modeling helps to identify the best suited process conditions with few experiments. We present a UF-DF-UF model to predict and describe product and membrane specific filtration processes.

In this study, high resolution X-ray computed tomography is applied to visualise and characterise internal geometry of packed beds and individual beads made of agarose, cellulose and ceramics. Pixel sizes from 3 µm to 32 nm enabled resolution of detailed features to analyse properties including porosity and available surface area, with positional based analysis able to identify physical phenomena such as wall effects.

This talk describes two directions toward therapeutic developments: 1) the design and production of proprietary protein libraries based on a small and stable scaffold with a screening procedure that has identified specific binders against difficult-to-drug targets, and 2) approaches to (a) producing a candidate drug-protein at scale and (b) high-throughput production method development for candidates from selections for functional screening rounds are described using tagless, affinity tag-based, and twin IEX approaches.

The overall purpose is to compare the performance of a resin reused to process a single product stream with the same mAb select Sure protein A resin type reused to process two product streams. The specific objectives of the project are to conduct a proof of concept study using protein A resin, 2 IgG product streams produced by a platform CHO cell lines and advanced analytical methodology using LC-MS. Here, we developed the experimental design to determine if the same yield and quality of product can be obtained compared to keeping the resin dedicated to the one product stream only.

A modern process development approach implementing QbD principles will be presented which is very relevant to ensure process understanding

Biopharmaceutical proteins (e.g. monoclonal antibodies) are important therapeutic medicines for different human diseases such as oncology. In this presentation, the USP bioreactor will be directly integrated into the DSP capture column so that the expressed monoclonal antibody can be directly purified on the capture step consisting of a disposable cell Tolerant Radial Affinity Chromatography (cTRAC) column and the cells efficiently removed as waste in closed disposable bags.

We discuss how continuous multicolumn chromatography for downstream processing of biopharmaceuticals can be designed for improved performance using model-based state-of-the-art optimisation tools. The aim is not only to maximize process throughput but also to explore the possibility of reducing solvent consumption, increasing product concentration, and, if possible, reducing the number of steps of the operating cycle. Concrete examples of the increased productivities and cost savings benefits of using optimised continuous multicolumn chromatography are given.

The CODOBIO consortium consists of nine industry partners, eight universities, one research organisation, a regulatory institution and a business consultancy, and has developed a research and training programme including relevant scientific/technical and transferable skills trainings. This presentation will review the cutting-edge science and future industrial applications of the findings.