Real-Time Process Management System Reliable to Reach Target Final Concentration

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The results found that repeatability testing found all 15 processes to be with in specification for target final concentration.

After using a process analytical technology (PAT)-automated tangential flow filtration (TFF) system that is controlled by real-time concentration measurement for ultrafiltration and diafiltration (UF/DF) processes, it was found to be an innovative solution for companies looking to automate their TFF process and increase process control, according to a poster study from Derek Carroll and Teva Smith from Repligen, which was presented at INTERPHEX 2023 between April 25-27 in New York City.

Using real-time concentration management is intended to ensure consistent targeted concentration results, insensitive to the types of variation commonly seen in mass balance-only systems. Further, automated process control is demonstrated for various final concentration endpoints, which suggests a better solution for the UF/DF process with key advantages over existing methods, according to Carroll and Smith.

Carroll and Smith used the Repligen real-time process management system (RPM) automation, which is driven by an in-line variable pathlength UV/Vis device, the CTech FlowVPX system. This system’s search algorithm assigns a collection start value of 1 absorbalance and measures 5 to 10 decreasing pathlengths to generate a slope value, according to the poster.


Carroll and Smith then introduced the KrosFlo KR2i RPM System, which utilizes Open Platform Communication-United Architecture (OPC-UA) to provide seamless PAT-driven process control with two-way communication between each device within the system. The RPM system using innovative PAT and OPC-UA reduces user input, greater process control, and reliable process output.

The objective of the study was to integrate an automated TFF process based on real-time concentration, and the study included testing the efficacy of the systems automation via repeatably and post-run mixing outcomes. To achieve this, the FlowVPX variable pathlength spectrophotometer and KrosFlo KR2i TFF system conducted a total of 15 UF/DF processes. The UF/DF runs were conducted using bovine serum albumin (BSA) in replicates of three with starting concentrations 5, 7.5, and 10 mg/mL. The final target concentrations for the processes were 50, 125, and 200 mg/mL. A method was then developed to create parameters for each item to react. The endpoints for concentration stages of the process were being controlled through the FlowVPX concentration measurements, according to the poster.

The results found that repeatability testing found all 15 processes to be with in specification for target final concentration. Further, the success rate for all process at varied start values and final concentration for KR2i RPM system emphasizes the sensitivity and reliability of PAT-based automation. The study highlighted that 12 out of the 15 processes to be within -0/+5 specification for target post run mixing concentration. Higher flux and lower final pool volume runs were more susceptible to over concentrate, while lower flux and higher final pool volume runs were susceptible to under concentrate.

The poster authors conclude that real-time concentration measurement provided by the FlowVPX System ensures reliable concentration readings, mitigating the types of variation found in traditional mass balance setups. They mention that future studies for the RPM system will be regarding post mixing optimization and novel modality testing.

Source: Carroll, D and Smith, T. Automated PAT-Driven TFF System Using In-Line Concentration Monitoring to Control the UF/DF Process. Poster. INTERPHEX 2023. New York, NY. April 26, 2023.