In a recent study presented at INTERPHEX 2023 in New York City, Derek Carroll and Teva Smith from Repligen showcased the effectiveness of a Process Analytical Technology (PAT)-automated Tangential Flow Filtration (TFF) system in achieving precise final concentration targets. Through the use of real-time concentration measurements for ultrafiltration and diafiltration (UF/DF) processes, companies can enhance automation and elevate process control standards significantly.
The implementation of real-time concentration management offers a groundbreaking approach to ensuring consistent final concentration results, independent of the variations typically encountered in mass balance-only systems. By incorporating automated process control for different final concentration endpoints, the UF/DF process stands to benefit from improved reliability and efficiency compared to conventional methodologies.
Carroll and Smith leveraged the Repligen real-time process management system (RPM), which integrates an in-line variable pathlength UV/Vis device known as the CTech FlowVPX system. This system’s innovative search algorithm initiates measurements with a specific absorbalance value and proceeds to calculate slope values by adjusting pathlengths, streamlining the concentration monitoring process.
Introducing the KrosFlo KR2i RPM System, Carroll and Smith demonstrated the utilization of Open Platform Communication-United Architecture (OPC-UA) to facilitate seamless PAT-driven process control. This two-way communication system between devices within the RPM setup minimizes manual inputs, enhances process control capabilities, and ensures consistent and reliable process outcomes.
The study’s primary objective was to establish an automated TFF process based on real-time concentration monitoring, with a focus on evaluating system automation through repeatability and post-run mixing assessments. By conducting a series of 15 UF/DF processes using the FlowVPX spectrophotometer and KrosFlo KR2i TFF system, the researchers tested the efficacy of the RPM system across varying concentrations and endpoints.
Results from the study revealed the exceptional performance of the RPM system, with all 15 processes meeting the specified target final concentrations during repeatability testing. Moreover, the success rate across different start values and final concentrations underscored the precision and reliability of PAT-driven automation. Notably, 12 out of the 15 processes achieved concentrations within the -0/+5 specification for post-run mixing, indicating the system’s robustness.
The authors of the poster stressed that real-time concentration measurement, as enabled by the FlowVPX System, plays a crucial role in ensuring accurate concentration readings and mitigating the variability associated with traditional mass balance setups. Future studies on the RPM system are set to explore post-mixing optimization strategies and novel testing modalities to further enhance process efficiency and control.
By embracing real-time monitoring and automation technologies in UF/DF processes, pharmaceutical companies can elevate their production standards, ensuring consistent and reliable final concentration outcomes. The integration of advanced PAT-driven systems like the RPM setup not only optimizes process control but also paves the way for enhanced efficiency and efficacy in pharmaceutical formulation processes.
Tags: process analytical technology, filtration, automation, formulation
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