Buffers are used in a variety of bioprocessing steps, ranging across multiple product recovery, purification and formulation processes such as diafiltration and chromatography. The use of buffers within downstream processing is particularly important as they are used to protect proteins from variations in pH and to ensure
that proteins interact correctly with various media to maximize performance of the specified purification process. Thousands of liters of buffers are produced each year for use in the manufacturing of biopharmaceutical products in clinical or commercial-scale processes, which requires a large resource input from the operator’s time producing the buffer solutions, to the facility space for storing the vast amount of buffers created, and the logistics of using them across the unit operations.
Within traditional facilities, multiple buffers of varying specifications are made for bioprocessing operations. Buffers are generated in vast quantities (a typical monoclonal antibody (mAb) process could require approximately 2,000 L of a buffer, or greater than 100,000 L of buffer per batch depending on the mAb titer, and the bioreactor volume) and are stored in large containers with significant footprint within the bioprocess facility until use. More buffer is subsequently created where needed, keeping buffer equipment at high utilization levels. This applies certain pressures on the buffer preparation operators, as well as the facility, to ensure buffers are readily made and can be stored efficiently. If multiple batches of buffer are required for a bioprocessing step, there is a risk of batch-to-batch variability which adds resource and time pressures as extra quality control (QC) procedures are required for each additional batch. In addition, there is an increasing consumables and cleaning costs associated with current buffer preparation systems, in order to ensure there is minimal risk of buffer contamination.
To optimize the buffer process, the Allegro Connect buffer management system (BMS) can be used to provide users with an efficient and optimized design for buffer management. The Allegro Connect BMS is an automated in-line buffer dilution system designed to manage the production of diluted process buffers ondemand and just-in-time from 5x to 20x stock buffer concentrates to feed various unit operations. The system consequently reduces the operator labor time, the facility space requirements and logistical bottlenecks when compared to traditional buffer management approaches, improving overall flexibility and ease-of-use.
In this study, the capacity for the Allegro Connect BMS to produce multiple diluted buffer solutions from stock buffer concentrates using one single-use flow path for bioprocessing was evaluated. This required the dilution of multiple pre-made stock buffers to desired specifications using the Allegro Connect BMS.
Results from the study demonstrate the system functionality to switch between multiple different buffer concentrates with minimal downtime on the system using the same single-use flow path. The findings also establish how applying a fast, effective flush between each buffer dilution can ensure the flow path was suitably cleaned and maintained minimal contamination risk.