Process Intensification Pushes SUTFF to the Limit
Can the single-use equipment employed in TFF handle the increased speeds and volumes delivered by process intensification?
This article is posted on our Science Snippets Blog
The biopharmaceutical landscape is currently undergoing a transformation. The emergence of new modalities, the growing uptake of single-use equipment, and the increasing use of process analytics are just some of the trends contributing to changes within the industry.
These features, coupled with significant growth and competition within the sector, force drug developers to reassess their manufacturing processes and consider new operational approaches to keep up with increasing demands.
Keeping Pace Requires Process Intensification
New operational strategies, such as employing process intensification (PI) principles, allow developers to increase their productivity and efficiency and reduce their time-to-clinic and time-to-market. While these intensification strategies will help satisfy key business drivers, such efficiency improvements may spark some practical concerns; how will the process itself be impacted?
Maximizing Scale and Speed with Intensified Single-Use Tangential Flow Filtration (SUTFF)
Increased efficiency typically is accompanied by faster processing and | or larger working volumes, which could thrust scientists (and their equipment) into unknown territories. They will need to determine whether the facility’s existing setups– including instruments, equipment, and single-use (SU) consumables - can handle this intensified workload.
One area in which increased speed and scale are of significant importance is in single-use tangential flow filtration (TFF) process steps. Employed in both up- and downstream process steps, TFF is a rapid method to separate biomolecules based on size. TFF is a technology applicable for harvest, clarification, purification, and concentration procedures. Understanding how increased volumes and flow rates impact TFF equipment is important to ensure process steps remain robust as production and process intensifies.
Testing the Limits
To fully support our industry partners as they work with greater volumes and speeds, Sartorius colleagues performed application testing to test the capabilities of our single-use (SU) Flexsafe® Pro Mixer bags, which can serve as recirculation vessels in SU TFF setups.
These tests had two objectives: first, to demonstrate the upper limits of the Flexsafe® Pro Mixer bag, and second, to determine the optimum setups for effective TFF when working with volumes and speeds higher than typical values.
What Could Go Wrong with SUTFF?
To understand the potentially demanding effects of the high recirculation flow rates (up to 5,000 L/hr), our scientists carried out application testing across three use cases where there was a high potential for failure.
Liquid surface breakage (i.e., a fountaining effect) caused by high recirculation rates can introduce air to the liquid, causing foaming. Foaming is known to damage proteins, which can reduce product yields.
Tube collapse can occur when high vacuum pressures are caused by high flow rates between the recirculation bag. This compromises the integrity of the setup
Deformation of the recirculation bag may occur upon high permeate flow rates, leading to folds and creases in the bag and inefficient mixing.
As well as testing the potential for these issues, we also wanted to guide how best to set up TFF systems while maximizing speed and volume. For this, we set up four flow paths (Figure 1) and tested their performance.
Figure 1 – Flow path designs tested across the use cases
Knowing Your Limits is Essential for Process Integrity
An important consideration when making any change to a process is the limits of equipment and consumables. This is especially true for next-generation facilities that use process intensification strategies coupled with SU solutions to produce and purify their product.
Our findings suggest that commonly used single-use tangential flow filtration setups remain powerful tools, even at the high speeds, volumes, and concentrations demanded by the biopharmaceutical market today. Read about our findings for each use case and our expert guidance on handling increased speeds and volumes in our application note.
