To sustain the rapid expansion of biopharmaceuticals whilst preserving their quality, the Quality-by-Design (QbD) initiative was introduced, which has process intensification as a main pillar. Process integration and continuous operations are valuable strategies towards consistent product quality and high throughput. However, digitalisation is the keystone to express their full potential as it allows a model-based process control, a reduction in time-to-market and costs, and fulfillment of the QbD guidelines.

Biopharmaceutical industry traditionally relies on pharmaceutical manufacturing practices to monitor processes and release products. The use of Process Analytical Technologies (PAT) can improve the process monitoring and control, and increase the process understanding. PAT also enable real-time control when integrated into a digital twin. This talk is concerned with the implementation of PAT and development of digital twins in GSK for purification processes.

In Integrated continuous biomanufacturing (ICB), the startup and shutdown depends mainly on the residence time distribution (RTD). A wide RTD also renders a fast process in a slow start-up and shutdown phase. The removal of surge tanks between unit operations, by the adoption of tubular reactors, maintains a continuous harvest and mass flow of product with the advantage of a narrow RTD. Continuous precipitation coupled with continuous tangential flow filtration is a cost-effective alternative for the capture of recombinant antibodies from crude cell culture supernatant.

Switching from standard fed-batch processes to intensified continuous manufacturing (CM) can significantly improve the cost-effectiveness of biologics production. CM processes are designed to operate continuously, with uninterrupted medium exchange and perfusate flow supply end-to-end. This is made possible through unit interconnectivity, where downstream flowrates are determined by the perfusate titer using process calculations. Different CM technological advances will be covered in this talk from novel process knowledge management tools for a holistic control to mass flow tracking and new walk-up development stations at the unit operation level. Developing and eventually implementing these initiatives will contribute towards field advancement.

• Implementing Digital transformation
• Role of AI/ ML in Bioprocessing
• Shared experiences​

This presentation will explore some of the challenges associated with developing long perfusion processes with stable product quantity and quality output over time. The first part will focus on the simultaneous reduction of the bulk fraction (bleed) removal needed to maintain the biomass and different methods will be described. The second part will cover filtration limitations (flow rate, sieving, clogging) and will describe alternatives to retain cells in the bioreactor in combination with bleed reduction. A continuous single-use centrifuge for cell retention was, for example, tested at pilot-scale.

Scaling-up a bioprocess for manufacturing is complex and the impact of cell culture parameters influences manufacturing modalities. BioSolve process incorporating multi-objective Bayesian optimisation is used to analyse the complex design space to help identify optimal solutions. This case study identifies optimal configurations for fed batch, perfusion, or intensified fed batch. The outcomes of the optimisation studies identify those factors that maximise economic, and sustainable benefits.

The ICH Q13 guideline provides scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM) of drug substances and drug products. This presentation will discuss the application to biomanufacturing.

Shift towards continuous bioprocessing relies on availability of robust real-time sensors enabling monitoring and control. Soft sensors are utilized where direct measurement is not possible or practical. Raman spectroscopy has emerged as a prominent soft-sensing technique, but road blocks to wider deployment remain, such as limited model transferability between processes, scales, or instruments. This talk will explore common causes of lack of transferability, their classification, and potential mitigation strategies.

Emerging technologies are at the forefront of promoting a sustainable message by delivering plausible environmental standards whilst maintaining efficacy and economic viability. Additive manufacturing processes are highly customisable, allowing for their optimisation in terms of sustainability, from reducing printing time to reducing material usage by removing supports. Microfluidics too are supporting sustainability via reduced material wastage and providing a sustainable means for point-of-care analysis.

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.

As the human population increases, the demand for biotechnologically produced, value-added products rises. Facing the drastic climate change, processes require severe transformation to produce fewer greenhouse gas emissions at lower water consumption. Continuous bioprocessing allows us to tackle these issues. In my talk, I will demonstrate the potential of continuous bioprocessing for targeted-enzyme production with diverse microbials.

In this talk, a fully continuous microbial production process involving a two-stage bioreactor system in combination with membrane filtration and MCC will be presented. By utilising mechanistic knowledge and machine learning algorithms, the entire process chain is modelled and optimised while the effect of each unit operation on the full control strategy is considered. This approach has the potential to impact the production of pharmaceuticals, industrial enzymes, and novel food.