Fibro PrismA is a new type of medium for the purification of mAbs where MabSelect PrismA has been coupled to fibers. The cellulose fiber matrix ensures fast mass transfer by convective flow that allows for high binding capacity and very fast residence times. The suitability of the Fibro PrismA capsules is evaluated for research purposes in R&D projects and for phase I GMP production.

The aim of this work is to present a procedure for comparing technologies for chromatographic purification. The case study is purification of a monoclonal antibody (mAb) using IEX chromatography. Based on batch chromatography experiments a packed bed adsorption model was developed. Using simulation, the batch process was then optimised and compared with a twin-column Counter-current alternative process (MCSGP). Optimal conditions were tested experimentally and compared.

Finding efficiencies across downstream processing steps and cost-effectively aligning the productivity of downstream production with upstream yields require complex analysis and optimisation. This presentation elaborates on the key aspects of downstream processing, looking at different areas where improvements by new techniques and new technologies could be made, from current process chromatography technologies, new powder and liquid handling strategies to raw material data analysis.

The DuoBody platform is a versatile and dependable technology for generating bispecific antibodies. Unlike other bispecific antibody platforms, the process is based on controlled Fab-arm exchange, which is performed post-production using purified monospecific antibodies. The process yields bispecific antibodies that retain the molecular structure and quality attributes of therapeutic IgGs. Case studies are presented detailing downstream processing approaches in the development of a range of bispecific antibody therapeutics

I will present the economic and ecological benefit of the novel E. coli X-press strain for downstream processing in direct comparison to the industrial standard E. coli BL21(DE3). Extracellular protein production with E. coli X-press holds high potential to reduce overall downstream expenses due to reduced capital charge, lower impurity load and consequently better chromatographic performance.

To determine viral clearance efficacy of biomanufacturing steps, viruses are “spiked” into in-process solutions, processed and analyzed for reduction.  Due to the infectivity of these viruses, studies are conducted in BSL-2 facilities.  Costs and logistics limit analysis during process development.  Discussed here are results from several studies that utilized a non-infectious Mock Virus Particle (MVP) as an MVM surrogate.  The results demonstrated the value to be gained from such a QbD approach during process optimization.  

The objective was to apply excipients, like sugars, polyols and PEG4000 in buffer systems, to study their impact on several aspects during Protein A chromatography and virus inactivation. The results include their effect regarding chromatographic performance, protein stability and viral inactivation. The results show that the addition of excipients can have a beneficial effect for the purification during Protein A chromatography and virus inactivation, without harming the subsequent chromatographic steps.

The attraction of high flow rates offered by membranes used in affinity chromatography has traditionally been offset by limited binding capacity and scalability for process development and manufacturing. Offering flexibility of binding capacity versus residence time provides a solution to developing rapid cycle protocols.

We show how a switch from a batch-operation mode to hybrid-continuous mode at Sanofi enables reducing buffer and waste amounts as well as resin costs, with two therapeutic proteins in the development and clinical manufacturing stage, also considering an adequate control strategy and a specifically designed virus clearance study to mimic the process in a CRO lab.

The high binding capacity and convectional flow path of single use chromatographic membrane solutions allow for smaller footprint unit operations, compared to traditional resin-based columns. High performance systems enable process intensification and simplification, which result in higher yield and lower overall manufacturing costs. In this presentation, we introduce a new hybrid AEX technology, combining a Q-functional non-woven and a guanidinium functional membrane which performs across a wide range of operating conditions.

Continuous integrated manufacturing can be achieved of biopharmaceuticals has been achieved by converting batch unit operations into a pseudo continuous operation. Here we demonstrate a real fully continuous operation and a monitoring and control concept for production of antibodies. The perfusion culture is directly linked to a continuous precipitation and virus inactivation in a single line. The economic advantages for such a process will be also discussed.

A point often overlooked when transforming from batch to continuus is the transformation only “shrinks” the unit operations itself, while the necessary hold tanks and demand of process materials are unchanged or drastically increased. We demonstrate a radical approach of a continuous on-demand reconstitution of media and buffers directly from solids in lab scale. This offers superior modularity, flexibility and opens new playgrounds in up- and downstream processing.

The COVID-19 pandemic inspired new approaches to vaccine manufacturing. Using a novel platform technology, vaccines were delivered to the threshold of regulatory approval with unprecedented speed and outstanding efficacy. This presentation will explore how mRNA and other platforms such as pDNA and viral vectors may forever alter the course of vaccine manufacturing.

Continuous manufacturing of a monoclonal antibody is demonstrated using a fully disposable 500 L scale platform (MaruX^TM) in a non cGMP facility.  Using our cell line (ApolloX^TM) in conjunction with a commercially available Single-Use Bioreactor in perfusion mode, we successfully purified the monoclonal antibody from a bioreactor output of 1 kg per day using multi-purpose, liquid handling units (SymphonX^TM) for point-of-use buffer dilution and connected, intensified batch processing.

Updated presentation including the latest results that will describe the steps taken by a UK-based consortium of biopharmaceutical manufacturers to develop a fully automated and integrated continuous downstream purification platform. This will include a description of the system automation and the next phase of the project in which we are further developing the digital side of the system.

The presentation will address central challenges in digitalization and big data analytics in biopharma and will demonstrate the potential to provide systematically value through integration of smart digital technologies such as non-intuitive optimizers and digital twins into the work stream. The presentation will be based on several industrial use cases in USP and DSP showing benefits from software-assisted and –enabled process optimization, automation and tech transfer.

Since several years there has been a significant increase in cell culture productivity resulting in filtration feeds with higher protein concentrations potentially increasing aggregation formation and impacting filterability. However, at higher concentrations, the volume to nanofilter is smaller which means that the surface area needed is decreased. Benefits include reduced costs, processing time, and footprint. In this presentation, we will present several case studies of concentrations up to 60 g/L and demonstrate why Planova™ BioEX is the go-to filter.

Process optimization for tangential flow filtration is an underestimated and tedious task. We present a hybrid modelling solution trained on a minimal data set to predict the performance of ultrafiltration operations in different modes (from batch to continuous). The models can be used as a digital twin to simulate virtual processes to facilitate efficient process development.

As the field of virus-based therapeutics matures, with applications in oncovirotherapy, vaccines or gene therapy there is a need for higher efficient downstream tools that are scalable, efficient and suitable for automation. In this talk, we will report on the development of periodic counter-current chromatography purification processes for oncolytic and gene therapy targets highlighting the pitfalls and opportunities ahead.

As biopharmaceutical industry evolves towards intensified and continuous downstream processing, it is important to consider the ramifications of these changes on virus removal. This presentation highlights considerations for viral clearance of a flow through polishing step and how a virus filtration step can be adapted to accommodate intensified and continuous process conditions.