We have created an approach for optimization of mammalian cell perfusion process by smart substrate targeted feeding, providing high cell growth, viability, productivity, and low byproducts. This work is supported by scale-down bioreactors fully operated in perfusion: stirred tank bioreactor of 200 mL and ERBI bioreactor of 2 mL. For the substrate optimization (e.g., glucose, amino acids) it leans on design of experiment or digital twin approaches.

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.

Processes can be intensified at all scales and all dimensions and are not limited to commercial production only. However, that requires implementing approaches to achieve “more, with less effort, faster” already at the beginning. This presentation gives a comprehensive overview of strategies how to integrate process intensification through the whole product life cycle. The opportunities from early development to continuous process improvements will be summarized in this talk.

The drive to net zero and a more sustainable future requires an understanding of the impact of Process Intensification options in terms of sustainability and business efficiency. The latest process models evaluate facility efficiency (doses per unit volume of cleanroom), PMI, and total energy efficiency. Pre-release versions were used by process intensification team in NIIMBL to support sustainability assessments. In this talk, comparisons are made between standard fed-batch processes and intensified process options that include perfusion and continuous downstream operations and considers the impact of facility locations.

Environmental sustainability has been gaining more attention in the biopharmaceutical industry. So-called Green Metrics are used to calculate the environmental impact of processes. While they can give a rough estimation, there are still severe shortcomings. In this talk, metrics such as the Process Mass Intensity (PMI) and the Water Related Impact of Energy (WARIEN) will be examined and scenarios for improvement evaluated.

CSL Behring manufactures albumin in various concentrations that serve different medical needs. Interestingly, higher concentrations of albumin showed dark sediments, with copper sulphide (CuS) being the main component. Studies determined a Quality Target for copper (= 0.2mg/kg), which significantly delays formation of sediments. One method identified to remove CuS is the chelation and sequestration of metal ions by chelating agents. Here, a strategy using EDTA and a new chelator named EDDS was developed. For both chelators, low pH positively impacted proteolytic activity and improved binding capacity. Additionally, accelerated stability studies demonstrated that these chelators delayed the dark sediment formation significantly.

Biopharmaceuticals have experienced a rapid growth in the market. To sustain this growth while preserving the product quality, the Quality-by-Design (QbD) initiative was imposed, which has process intensification as a main pillar. This can be achieved through integrated continuous biomanufacturing. Process integration and continuous operations are valuable strategies toward consistent product quality attributes and high throughput. However, to express their full potential, digitalization stands as the keystone, allowing to reduce the time-to-market and costs, to fulfill the QbD guidelines, and to introduce a model-based process control. The opportunities and challenges of digitalization are then presented in the framework of biomanufacturing.

Digital Transformation is one of the keywords in the beginning of the 21st century. Companies, including biotech and pharma, now push forward to keep pace with customer needs and competitors. Here, we describe the pitfalls, pains, and gains in preparing, transforming, and executing digitalization in our labs, as part of sanofi’s global digital transformation.

Pharma manufacturing is still mostly focusing on the exploration phase of digital technology. The major goal of this presentation is to identify major drivers and challenges for digitalization and digital transformation in pharma manufacturing. Three main perspectives, namely technology, organization, and culture, as well as management and business strategy, will be highlighted. The results are based on extensive collaboration with several tens of pharma, biotech, and CDMO companies.

Several enabling technologies change the way we do pharmaceutical development: automation and digitalization, modeling and simulation. But especially the latter are not silver bullets, and it is important to have a closer look: why and when one might use them, which factors support a successful and sustainable implementation, and what it means for an organization to embrace these new ways of work.

The Centre for Process Innovation (CPI) is part of the UK High Value Manufacturing Catapult (HVMC). CPI has been, and is currently, involved in several continuous biologics manufacturing projects. Process analytical technology (PAT) is becoming increasingly important in biologics manufacturing. In this talk, I will discuss previous and current projects involving continuous manufacturing and the use of novel process analytical technologies (PATs).

State-of-the-art recombinant protein production with microbials is conducted in fed-batch cultivation. Switching to continuous processing would impose small-footprint manufacturing and increase the space-time yield compared to fed-batch processing. Still, industry and research struggle in achieving long-term microbial cultivations with stable productivity. Within this presentation, I will address reasons for fluctuating productivity in continuous processes, and discuss opportunities and how to overcome these challenges.