Email for more information

Company's other products

Email to a colleague

Printer friendly format

David Rubin Product Manager Millipore Corporation

Tangential flow filtration (TFF) is a separation technique used for clarifying, concentrating and purifying proteins. In TFF, the fluid is pumped tangentially along the membrane surface. Particles or molecules which are too large to pass through the membrane are rejected and returned to a process tank for additional passes across the membrane until the process fluid is sufficiently clarified, concentrated or purified. The cross-flow nature of TFF minimizes membrane fouling, thus permitting high volume processing per batch.

Traditionally, a TFF process involves time consuming and costly validation of both TFF system and cassette cleaning. Due to these concerns, many users are expressing strong interest in utilizing single-use assemblies in TFF applications. The use of disposable components would eliminate the need for membrane and system cleaning as well as mitigate risk.

Millipore Corporation recently introduced Mobius disposable TFF assemblies which offer flexible, self-contained solutions that help reduce validation and cleaning efforts, increase process speed, as well as mitigate risks. These assemblies are a complete, self-contained TFF flow path consisting of a process container, tubing, connectors, and disposable cassette manifolds that eliminate fluid contact from any reusable components. The assemblies can be integrated into a solution that includes in-line monitors, process pumps, filter cassettes and holders as well as optional controls and instrumentation. The system will be available as a manual version as well as a semi-automatic control version. Using disposable components in TFF processing provides many benefits without sacrificing robust manufacturing processes. Single-use TFF assemblies are most beneficial for those involved in early-stage manufacturing of MAbs, vaccines and gene therapies for several reasons: • Eliminate the writing, executing and reporting results of device and system cleaning protocols • Mitigate risk associated with multi-use TFF systems such as product cross-contamination, high bioburden and insufficient cleaning. Each of these items frequently lead to development and/or manufacturing delays, drains on resources, lost raw materials and in the worst case, lost intermediate or final product. • Reduce time-to-market by accelerating development process Contract manufacturing organizations (CMOs) will also find using disposable assemblies in TFF processing particularly useful. Often, CMOs have multiple clients but only one system on which to perform different processes. This use of a single system creates a concern about cross-contamination issues because the system must be thoroughly cleaned and validated between customers batches. The time and cost to perform this change-over is high and, if done improperly, can introduce contaminants into the process. Through the use of disposable TFF assemblies, cleaning and validation steps can be eliminated. Each client’s process is performed on brand new, never before used disposable components, which are then discarded after use. CMOs will then be able to reassure their clients that their batches are not at risk for cross-contamination.

Advantages of Using Disposables

By utilizing disposable TFF assemblies, risk is mitigated. If contamination is suspected in traditional TFF processing the entire process must be stopped and the problem investigated. This delay can be quite costly, especially if the batch has a short shelf life and can not withstand production delays. Additionally, delays in the schedule mean time has been lost in getting the product to market. Researchers who are pulled away from their jobs to investigate are no longer focused on their research and development work, thus leading to a decline in innovation and productivity. Recently, Millipore conducted a study to quantify the cost of risk associated with operating multi-use TFF systems. Feedback from over 40 customers located throughout North America and Europe indicated a common concern related to cleaning a TFF system or cassette. Approximately 35% of those with direct or indirect TFF experience have experienced prior cleaning problems which required over a month to resolve, on average. The direct costs resulting from the problem ranged from a few thousand to several hundred thousand dollars. The opportunity costs, in many instances, were even greater. Based on these survey responses, the (indirect) cost of risk associated with operating a TFF system is approximately $1000 per batch. An additional benefit of using disposable TFF assemblies is that cleaning and validating the system and cassette are eliminated. It can take weeks to create and write the proper cleaning validation protocols. Once the protocols are approved, they must be executed. By using disposable assemblies, no product comes into contact with the hardware, so these steps can be eliminated. Lastly, controlling bioburden levels is extremely important in the biopharmaceutical industry. High bioburden levels found downstream or during the final process step can cause the failure of an entire batch. Using disposable TFF assemblies eliminates the introduction of bioburden into the process, thus preventing delays in manufacturing schedules.

Conclusion

By introducing single-use assemblies such as Mobius into TFF processing, downtime between biopharmaceutical runs is reduced, cleaning and validation efforts are minimized, and speed to market is increased. Optimizing TFF systems will lead to more robust manufacturing processes with improved yield and cost savings.