Large Scale Buffer Management System

BioProcess IC System is a buffer management system that allows on demand production of buffers from single-component, highly concentrated stock solutions of salt, acid, and base, diluted with water using inline conditioning (IC) technology. Accuracy is ensured through dynamic control using different modes of feedback control.

• Automatic production of buffers from concentrated single-component stock solutions saving time, resources and buffer volumes.
• Dedicated pump lines for acid, base and salt with several inlet ports to enable formulation of different buffer families in one production run.
• Automatic switch between buffers without need for manual intervention to allow for consecutive buffer production. During switching, buffer out of specification is automatically directed to waste.
• For accurate formulation, feedback control of the final buffer is performed inline using either recipe and flow, pH and flow, or pH and conductivity.
• The buffer system can either be integrated with the chromatography column replacing the chromatography system, or used as an independent buffer producing unit in the technical area.
• Both inline dilution and inline conditioning capabilities.
• Operated using UNICORN™ control software or integrate into Delta V automation platform.

Inline conditioning addresses the challenges with large floor space requirements and inherent variability in manual buffer preparation. Automating the process allows to produce buffers when they are needed, streamlining buffer preparation. The system can be optimized to fit the process and facility by either integrating it into the chromatography unit operation or by using it as a standalone buffer preparing unit. To further intensify the buffer preparation process, ready-made stock solutions can be used, eliminating all raw material handling and manual preparation of stock solutions. Advantages of using single-component stock solutions as opposed to concentrated buffers for dilution, are that the common ion effect will not limit the maximum concentration to the same extent and there is no need to handle pH and conductivity shifts due subsequent dilution.

Hardware

The skid can be built as a buffer station or with both buffer production and chromatography functionality. The buffer system standard components include dedicated pumps for acid, base, salt, additives and WFI (water for injection), air trap, multiple inlets and outlets, three channel multi-wavelength UV, conductivity and pH sensors and CIP inlets (for cleaning-in-place). Optional components include dual filter housing, feed pump and titration pump. The hardware is described in detail in the data file found in the Documents section or the link above. Product specifications are also found in the order table.

Dual pH probes are included for both controlling and monitoring the pH of the buffers being created. Each module contains a pH probe suitable for low salt buffers and a pH probe suitable for high salt buffers. This avoids the issue of salt memory which can impact the measurement accuracy of the solutions. If the skid also has chromatography functionality, a fifth pH probe is also included in the post-column position.

The system is designed to quickly prepare buffers at the correct pH and conductivity. If the readings are not within range, the flow is diverted to waste, while the system adjusts the component proportions. Once the buffer is reading within range again, the flow will resume toward the buffer containers or downstream equipment.

A built-in CIP manifold allows easy cleaning-in-place of the system.

Using the system for chromatography

When configured for both buffer production and chromatography, the system includes the components above, plus column connections and can use an optional bypass valve to allow switching between two columns without removal of either column. Additional UV, conductivity and pH sensors are placed after the column position. Both AxiChrom™ columns and ReadyToProcess™ prepacked columns can be used.

An optional titration pump can be added after the column connection to enable pH adjustment of the product eluted from the column.

Control software

The system includes UNICORN™ software preinstalled on the integrated HMI (human-machine interface), enabling standalone operation and simplified system control.

The software is designed according to GAMP 5 guidelines and can be used in a manner that follows 21 CFR part 11 requirements.

With dynamic feedback control, the BioProcess™ IC system enables correctly formulated buffers from individual components, independent on stock variability. The interactive process picture displays key run data, allowing the user to set and view manual instructions and alarm limits for components. There are three feedback control modes, using flow, pH and conductivity to monitor and adjust the buffers to the desired formulation.

For users who require buffer production equipment to be used on their facility’s plant-wide automation platform, BioProcess™ IC systems can be customized with a distributed control system or can connect to automation options via Open Platform Communications-Unified Architecture (OPC-UA). 

Cytiva offers a comprehensive range of service support, regulatory services and application support.