Multispecific antibody-based therapeutics are complex biologics that require comprehensive CMC feasibility assessments to assess developability, minimise manufacturing risks, and ensure product quality, safety, and efficacy throughout the manufacturing process. This presentation will highlight key experiments and risk mitigation strategies for multispecific lead molecules at Numab Therapeutics, with the focus on upstream and downstream platform feasibility, stability studies, biophysical characterisation, and formulation approaches.

Rapid preclinical CMC processes are essential for accelerating antibody therapies to meet urgent medical needs. This presentation highlights innovative strategies to streamline CMC processes, including cell line technologies, automation, and data-driven approaches. With greater efficiency, shorter timelines, and consistent product quality, Genmab is optimising the development pipeline for its antibody, DuoBody, and ADC-based therapies.

Primary recovery of mammalian antibodies includes multiple steps; reducing this number can prevent product loss, save time, and reduce water usage and costs. Expanded Bed Adsorption (EBA) was developed for this purpose, though low titres and large volumes limited its effectiveness. We’ve brought EBA back to the future via a specialised PrA resin and method. With our setup, =50g of product per litre resin captured directly from bioreactor feedstreams.

Affinity tags are an essential tool for drug discovery and development. They are widely used in research but are rarely part of the biologic API. A potentially required proteolytic tag cleavage and removal requires additional processing steps and sourcing of complex raw materials. Self-removing affinity tag systems based on split inteins display a promising option for research applications but also for large-scale manufacturing. Focus of this presentation is the evaluation of three different solution providers’ tags and resins testing diverse proteins expressed in different production hosts.

The residence-time distribution is an important parameter to assess the performance of an integrated process. It shows how fast the process is in steady state and how process disturbance propagates. Understanding the RTD also helps to design efficient processes. Examples will be provided.

Continuous capture chromatography (cSMB) can be used for capturing monoclonal antibodies offering higher resin utilisation, higher productivity, and lower buffer consumption than traditional single column capture processes. The design of cSMB processes is more challenging than the design of batch processes because each “switch” of a given column affects the subsequent switch. We have developed an iterative solution using different flow rates, breakthrough curves, and pressure/flow data as model inputs which results in significantly higher productivities compared to the standard approach. The effect was confirmed for a given in-house model process where productivities could be increased by approximately 50%.

As bioprocessing evolves, companies must adopt next-generation technologies and intensification strategies to stay competitive. This talk will explore how process intensification, digital tools, and PAT (Process Analytical Technology) can accelerate time to market, reduce costs, and support sustainability. By outlining a strategic roadmap for integrating these technologies, demonstrating how companies can optimise their processes and scale effectively. Giving actionable insights into building a holistic approach to process improvement—balancing speed, cost-efficiency, and environmental responsibility.

Integrated continuous bioprocessing boosts biomolecule production efficiency, reducing material use, equipment size, and carbon footprint. However, scaling is costly, necessitating innovative screening methods. Microfluidic devices accelerate biomanufacturing by testing many variables with minimal reagents and time. Most studies optimise individual operations rather than entire processes. An integrated microfluidic platform simulating bioprocessing has been developed, incorporating modules for production, chemical lysis, and ATPE to optimise both individual and combined operations.

Small scaffold proteins engineered for improved half-life and protease resistance require bespoke purification schemes. The SXkmer scaffold presents single constrained hypervariable peptide sequences for target binding, and rather than include affinity tags for downstream purification, we aim to utilise charge characteristics of the protein to achieve high-level purity from bacterial expression systems without compromising protein function or requiring post-purification tag cleavage. Examples from a GPCR targeting programme will be presented that describe terminal Cys mutants for labelling and positional mutants for functional & bioavailability changes.

Are you familiar with protein or DNA separation with magnetic particles on a small scale and are wondering whether this can also be applied on an industrial scale for the rapidly growing field of biopharmaceuticals? Using a pilot-scale magnetic separator and the integration of Pharma 4.0 principles, we show how the process control works and how the purification process of antibodies from CHO supernatants is optimised.

Affinity and mixed-mode ligands are important for capture steps in downstream processing. The talk shows how can we offer tailor-made ligands using a vast chemical space for ligand discovery and optimised ligand production methods.