At our clinical manufacturing site here in Switzerland, we introduced novel Process Analytical Technologies (PAT) for Biologics. For this, we successfully established a variety of PAT tools in a GMP compliant way for upstream and downstream processing, for example Endress+Hauser Rxn4 and Repligen FlowVPX. This allows us to deploy advanced process control strategies and to support improved manufacturing processes. We would like to present our experiences with these tools.

To achieve ambitious goals in reducing global warming, it is crucial to couple deliberate actions with a resolute mindset of stubborn optimism. At Novartis, we embrace this powerful combination as we strive to make a tangible impact through driving sustainable initiatives, including the design of resource-saving manufacturing processes. In this presentation, we will showcase process improvements that not only drive efficiency but also yield remarkable reductions in carbon emissions.

This presentation explores the techno-economic viability of continuous bioprocessing, comparing it with batch processes in terms of cost-efficiency, scalability, and technological readiness. Through examining recent advancements and economic analyses, it evaluates whether the benefits, such as increased yield and reduced downtime, justify the initial high investment. The study aims to provide a clear economic perspective to aid in decision-making for adopting continuous bioprocessing in pharmaceutical manufacturing.

• Implementing advanced control process technologies to continuous processes
• Beyond monoclonal antibodies (mAb): applying continuous manufacturing to a diversified pipeline
• Breaking barriers to enhance adoption of continuous manufacturing: how?

Around 80% of costs and environmental impacts are set early in development. New digital process facility models can now predict the Cost of Goods and CO2e emissions at this stage. These models evaluate different technologies and methods, understand trade-offs, and optimize downstream processes to cut costs and reduce environmental impact, thereby maximising benefits. Assessments of different DSP intensification approaches are used to illustrate these models' utility.

In this talk we will delve into the topic of green metrics to measure and improve sustainability of biologics. In early development, emphasis is typically placed on mass-based metrics, whereas in commercial production the focus often shifts to carbon footprint. How do we address the challenge of finding suitable metrics that are simple to calculate yet effectively predict commercial emissions? How can software like BioSolve help?

Genome-integrated, as well as growth-decoupled E. coli expression systems, enable continuous protein production. Efficient implementation requires suitable process strategies for cultivation, and product recovery and purification. The presentation will show two case studies inclusive of an economic evaluation with standard fed-batch as benchmark. We will also present results from a cutting-edge, highly-funded, innovative R&D project named ECOnti.

The ECOnti consortium was created to advance continuous manufacturing using Escherichia coli (E. coli) with a capacity of up to 10 litres per batch. By leveraging advanced model predictive control and conducting detailed economic modelling, our goal is to elucidate the cost-effectiveness of continuous manufacturing frameworks as opposed to conventional batch-based approaches.

An innovative approach for integrated, continuous protein production will be presented, focusing on dynamic process modelling and simulation. By utilising physics-informed machine learning, we explore the possibilities of characterisation, optimisation, and predictive control of a bioprocess chain involving a two-stage bioreactor system in combination with membrane filtration and multi-column chromatography (MCC). These findings extend their impact to a multitude of industries, including pharmaceuticals, industrial enzymes, and cultured meat production.

Virus-like particles (VLPs) are highly efficient vaccines and possible drug delivery vehicles. Their purification is challenging with low recoveries, making them relatively expensive. This presentation outlines the main challenges during downstream processing and basic design and process principles for continuous and integrated purification of non-enveloped VLPs that can be used as vaccines.

mRNA-based therapeutics have emerged as cutting-edge technologies for treating various diseases. Current downstream processing, which relies on a series of chromatography methods and TFF, remains challenging with low yields and significantly impacted final production costs. We will present our integrated and continuous manufacturing process for mRNA production and purification. We are investigating novel methods for continuous mRNA precipitation-based purification, including various precipitating agents, and following precipitation with continuous flow filtration.