A recent article published in the Journal of Membrane Science presents a new approach for implementing a robust single-pass tangential flow filtration (SP-TFF) operation in biomanufacturing. The authors introduce a process analytical technology (PAT)-based strategy that integrates and continuously applies SP-TFF for a duration of six days, either in batch or continuous format.
The proposed solution involves the use of robust control algorithms to maintain a consistent protein concentration in single-pass ultrafiltration (SP-UF) and achieve the desired buffer exchange in single-pass diafiltration (SP-DF). This novel PAT-based filtration technique can be applied in therapeutic bioprocessing, and its effectiveness is demonstrated through an integrated and continuous operation of SP-UF and SP-DF.
The authors emphasize that this bottom-up SP-TFF PAT-based technique is the first of its kind, preventing membrane fouling and ensuring the maintenance of target process and product attributes in robust SP-TFF operations within both batch and continuous bioprocessing settings.
Bench-scale experiments were conducted to characterize the SP-TFF process and develop semi-empirical models based on the feed flux and feed concentration. These models allowed for the identification of optimum filter sizing and SP-TFF performance. With the implementation of robust process control, the desired protein concentration in SP-UF could be achieved, and consistent concentration and targeted buffer exchange values in SP-DF could be maintained.
The adoption of integrated and continuous biomanufacturing (ICB) offers several benefits over traditional batch methods in fed-batch and perfusion bioreactors. These advantages include reduced facility footprint, compatibility with single-use technologies, consistent and homogeneous product quality, and decreased capital and operating costs. However, advancements in the final filtration steps of the purification process have been relatively limited compared to earlier stages.
In recent years, SP-TFF has gained favor over traditional TFF in both batch and continuous processes due to its ability to handle larger process volumes, eliminating potential bottlenecks in downstream purification operations.
The ability to perform continuous SP-UF and SP-DF is crucial for successful integrated and continuous biomanufacturing of formulated drug substances. The biopharmaceutical industry has been transitioning from traditional batch processing to ICB to achieve process intensification and agile manufacturing.
The paper highlights that recent advances in process intensification have led to increased cell densities in fed-batch and perfusion reactors, resulting in higher product volumes and titers. However, these productivity gains have placed constraints on downstream operations, necessitating greater flexibility in their design and processing capabilities while maintaining cost-effectiveness.
A significant advantage of the novel process analytical technology-based method described in the paper is its applicability not only in continuous biomanufacturing but also in batch or cyclic batch processes. It can be utilized for various modalities such as monoclonal antibodies (mAbs), fusion molecules, and enzymes.