The therapeutic antibody market demands scalable, cost-efficient manufacturing beyond conventional fed-batch processes. We present a hybrid fed-batch strategy integrating ATF perfusion of the inoculum with model-based process design, enabling high seeding densities and intensified productivity. This plug-and-play approach increased yields 4–6 fold (1.9 g/L to 10–12 g/L) while maintaining quality, reducing costs by ~60%, and proving robust across CHO cell lines—offering a sustainable, adaptable platform for next-generation biomanufacturing.

Real-time monitoring and control with Raman spectroscopy is dependent on calibration models that translate spectra to analyte concentrations. This is often performed by chemometric models that require extensive datasets, thereby hindering rapid implementation of PAT. This presentation will go over different methods we applied to support rapid calibration, as well as how different measurement conditions affect the spectra itself.

The Cell and Gene Therapy Catapult (CGTC) is advancing cost-effective, next-generation rAAV manufacturing by developing continuous and intensified upstream processes that enhance productivity, scalability, and consistency. Complementing this, process and mechanistic modelling, integrated with Process Analytical Technology (PAT) and automation, provides real-time monitoring, predictive insights, and adaptive control. Together, these innovations create smart-by-design platforms that accelerate development, reduce costs, and enable robust rAAV manufacturing at commercial scale.

Sustainability in biomanufacturing can be approached through intensification. Achieving higher efficiency production through more responsible use of resources requires process analytical technology and adaptive control to minimise waste and optimise yield. Here we present CPI's work in the intensification of biomanufacturing including the use of adaptive algorithms to drive process development. This approach will lead to more efficient production and therefore greater availability of therapeutics to patients

Transformative early process development unlocks significant cost and environmental benefits. Limited process data can be used for predictive, rapid, and scalable process optimisation by linking process knowledge, AI-conditioned databases, and innovative process digital-facility modelling—enabling new green metrics and manufacturing optimisation before Phase II. A mAb case study illustrates how process intensification and strategic modelling cut costs, material use, waste streams, and Scope 3 emissions.

Life cycle assessment (LCA) of existing antibody production systems, such as intensified and non-intensified bioprocesses, provides valuable insights into their environmental impacts, including raw material consumption, water usage and consumable material demand. Decreasing the environmental footprint of these processes prior to the subsequent product development is inevitable because the start of the development already creates accomplished facts for the entire future production. Assessing the entire upstream process from raw material to waste disposal, this data basis helps to identify ways to reduce the environmental footprint, supporting the transition to greener, more circular and more sustainable biomanufacturing practices.

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 including an economic evaluation with standard fed batch as benchmark.

Plasmid DNA (pDNA) underpins viral vectors, mRNA vaccines, and DNA therapeutics, yet production is limited by costly, low-yield batch processes. iCAP transforms this with a continuous, automated microbial platform integrating bioprocess intensification and digital intelligence. Using genetically stabilised E. coli and a growth-decoupled replication system, iCAP enables stable, long-term plasmid production in bioreactor cascades. Continuous alkaline lysis, chromatographic purification, and real-time digital twin–based control ensure high-throughput, low-variability recovery. Modular and scalable, iCAP reduces costs and environmental impact while supporting decentralised vaccine manufacturing and integrated therapeutic supply—setting a new benchmark for sustainable, next-generation plasmid DNA biomanufacturing.

Hybrid modeling workflows are transforming continuous microbial bioprocess development. In this presentation, we extend our previous case study to multiple products, integrating a two-stage bioreactor with inline lysis, membrane filtration, and multi-column chromatography. By leveraging mechanistic knowledge and machine learning, we demonstrate how such workflows accelerate development, reduce experimental load, and enable rapid transition to real-time control.

Raman spectroscopy is a powerful tool in process analytical technology (PAT) for bioprocess monitoring. However, developing accurate models is slow and costly. We propose an innovative strategy, where pure spectral fingerprints of target analytes are in silico added to calibration datasets. This approach eliminates extensive physical experiments, accelerates workflow, and improves adaptability across diverse bioprocess conditions. The method has potential to significantly streamline PAT model development while maintaining predictive performance.

In previous work, we demonstrated the benefits of harvesting oncolytic viruses during production e.g. using tangential flow depth filtration (TFDF). This approach enables integrated clarification within the upstream process, eliminating a downstream unit operation and enhancing both viral titers and productivity. Building on this, we present our results on high-cell-density perfusion cultures (>20 × 10^6 cells/mL) of HEK293 and avian cell lines (EB66 and CCE.X10) for the production of three different oncolytic viruses: Newcastle disease virus (NDV), herpes simplex virus type 1 (HSV-1), and a recombinant vesicular stomatitis virus–Newcastle disease virus chimera (VSV-NDV). We discuss virus-specific challenges encountered during intensification and strategies to maximise productivity and product quality.

The increasingly higher demand of viral vectors for gene therapy, such as rAAV, makes current state-of-the-art of biomanufacturing (batch, fed-batch) incapable of satisfying such needs. Continuous processes have been shaping the trend of biomanufacturing evolution, but so far have been modestly applied for rAAV production. Here, a continuous multi-stage bioreactor process was designed to produce recombinant adeno-associated viruses (rAAV) using the HeLaS3 producer cell line (PCL) infected with wild-type adenovirus type 5 (wtAd5). At downstream, cell lysis for rAAV release, DNA digestion, and lysate clarification, were also implemented in continuous mode, towards implementation of an end-to-end continuous rAAV biomanufacturing pipeline.