Protein Concentration Determination and Automation During Drug Product Dilution Processes Using FlowVPE System

Protein concentration is one of the critical quality attributes of fill-finished drug products, as it ultimately defines the dosage a patient receives. Process analytical tools are key in monitoring this attribute and are used to control the manufacturing process accordingly. This presentation will give an overview of the journey from initial laboratory feasibility tests of the CTech FlowVPE technology to implementation into an aseptic GMP facility for in-process control testing of biologics. In addition, the talk will highlight how the inline technology sheds new light on the manufacturing process and increases product understanding. Building on the availability of real-time continuous protein concentration data, next steps in the development and implementation of a future automated human-free process execution will be shared.

Speaker: Raf De Dier, Associate Director Advanced Technology – Janssen.

Evaluating the new CTech FlowVPX System for UF/DF-Protein Concentration (Bristol-Myers Squibb)

An evaluation of a beta version of the FlowVPX and Viper software was performed to determine it’s potential as an inline instrument for product concentration measurement during UF/DF operation, particularly high concentration UF/DF processes that are required for subcutaneous injection formulations (greater than 150 g/L). The FlowVPX has significant potential for GMP and commercial biologics manufacturing unlike the first generation FlowVPE, which was designed as a lab scale instrument. Extensive testing was done using small and pilot scale UF/DF operations with several biologic drugs molecules from the portfolio. The FlowVPX instrument demonstrated very good comparability with other A280 based protein concentration measurements for all molecules tested (six). From a technical standpoint the FlowVPX is a GMP ready instrument, and further testing for instrument robustness and software development is ongoing at present to potentially use the instrument in the GMP space within the near future.

Speaker: Jay West, Ph.D., Principal Scientist Biologics Process Development – BMS.

Biologics concentration measurement with the FlowVPX during the UF/DF process in drug substance mftg (Bristol-Myers Squibb)

The FlowVPX System was used as an in-line instrument for product concentration measurement during UF/DF operations, with orthogonal offline testing done to check comparability. The FlowVPX device has generated significant interest for high concentration UF/DF processes in particular (less than 150 g/L) since overconcentration can result in precipitation. The FlowVPX System has significant potential for GMP and commercial biologics manufacturing with the development of single use flow cells by the vendor. Extensive testing was done using small and pilot scale UF/DF operations with several biologic drugs molecules from the company’s portfolio.  The FlowVPX instrument demonstrated acceptable comparability (within 5% difference) with orthogonal A280 based protein concentration measurements for all molecules tested. Accuracy and precision were equivalent for all flow cells and scales tested, suggesting the FlowVPX can be a robust reliable in-line instrument in GMP settings.

Speaker: Jay West, Ph.D., Principal Scientist Biologics Process Development – BMS.

Model Predictive Control for automated biologics drug product manufacturing (Janssen)

This presentation focuses on the development, testing, and justification of an advanced control strategy for automating the dilution process during the formulation step in fill-finish manufacturing. The proposed control strategy is founded on precise, accurate and fast protein concentration measurements, all provided by the FlowVPE technology. Being able to rely on timely, high-quality concentration measurements, the novel strategy combines the FlowVPE implemented on-line with real-time data processing and modelling, to achieve immediate feedback control of the dilution process without the need for human intervention.  

Speakers: Janssen-Renata Pocitarenco, JSC Process Modelling and Marius Mueller, DPDS Analytical Development – Janssen.

CTech FlowVPE System in combination with MALS for Real Time Molecular Weight (RT-MW) Applications (Roche)

Multi Angle Light Scattering (MALS) can provide the real time molecular weight (Mw) of a pure solute or the average Mw of a solute matrix if the total concentration of the species is also available in real time. Analytical experiments with low protein concentration can use conventional fixed path length UV sensors, however these become saturated at the higher concentrations of manufacturing processes. The FlowVPE System enables the real time measurement of protein content in a wide concentration range, which can be coupled to MALS for RT-MW measurements. Besides a more agile process development, RT-MW can enable adaptive processing decisions and inform on product deviations.

Speaker: Andres Martinez-Roche, Post-Doctoral Scientist, Downstream Processing & Real-time Monitoring – Roche.

Application of Variable Pathlength Technology for Rapid Determination of Dynamic Binding Capacity (KBI Biopharma)

An ever-increasing demand for biomolecule-based therapies is driving biopharmaceutical companies to accelerate process development activities to remain competitive in today’s industry. Within the downstream process development space, affinity chromatography is widely used for primary capture of monoclonal antibodies, Fc fusion proteins, etc. Optimization of this step requires determination of dynamic binding capacity (DBC) for target protein molecule and can be a lengthy process using traditional methods. KBI Biopharma has applied the use of variable pathlength technology for rapid generation of breakthrough curves and determination of DBC for capture resin selection. FlowVPE, a variable pathlength UV detector from Repligen, is integrated with the chromatographic system for real time generation of breakthrough curves, reducing the time and cost associated with the development of the primary capture step. This technology helps accelerate the overall process development timeline.

Speaker: Rashmi Bhangale, Ph.D., Downstream Process Development Scientist – KBI Biopharma.

Implementing PAT strategy using in-line concentration monitoring in batch/continuous chromatography (Seagen)

As Seagen steps into next-gen processing, continuous processing has been one of their major area of focus for 2022. With the increasing production demands, process intensification requirements are increasing as well. To meet this, in-line process analytical technology (PAT) can enable comfortable processing. A steppingstone to this was our evaluation of VPX for further concentrating harvests and improving the chromatography efficiencies.

Speaker: Aishwarya Ramanan, Senior Research Associate – Seagen.

Bioprocessing Expert Panel Discussion Part 1 – PAT Implementation

Bioprocessing Expert Panel Discussion Part 2 – PAT Strategies