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. See this paper for more details. 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, allows 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). Visit the UNICORN™ software product page.
Equipment services
Cytiva offers a comprehensive range of options that can be customized to your asset-management needs and desired outcomes. Learn more about service agreements and life cycle support for your equipment.
Change Control Notifications
Our web-based Change Control Notification (CCN) service ensures that you are notified about changes that could potentially impact your product or process.
The CCN service is available for free by subscription at the Regulatory Support website.
