Advancing TFF for Small-Scale Biopharmaceutical Production (Webcast Recap)

Conventional benchtop systems for tangential-flow filtration (TFF) lack the features and functionality of industrial-scale units because they typically are designed for research, testing, and process development, not for manufacturing. As the biomanufacturing industry shifts toward personalized medicine and small-batch therapeutics, companies must rethink bench-scale TFF in applications involving new modalities.

Lucas Smith (product manager at Repligen) presented about the KrosFlo RS 10 TFF system in a recent Ask the Expert webinar. The system is the first automated, bench-scale TFF system built specifically for current good manufacturing practice (CGMP) production. The unit has the same components, controls, and capabilities as a large-scale TFF system used in commercial manufacturing, including all valves, inlets, and outlets for complete end-to-end automation of the entire TFF process, such as buffer and caustic flushing, integrity and permeability testing, ultrafiltration and diafiltration (UF/DF), and product recovery.

Smith’s Presentation

Compatibility: Considering the variety of applications in which bench-scale systems are used, each with its own processing requirements, filtration systems should be flexible enough for multiple configurations. Repligen designed the RS 10 system with a variety of feed pump options, enabling users to tailor the system around their processes and not the other way around, including a mag-lev centrifugal pump for shear-sensitive molecules and a diaphragm pump for higher pressures and moderately shear-sensitive molecules. The device also can be equipped with a peristaltic pump, which decreases costs by eliminating the need for a single-use pump head. The RS 10 system supports both hollow-fiber filters and flat-sheet cassettes. Users can swap out holders and plug in a different filter quickly.

ProConnex preassembled flow paths by Repligen are designed for ease of use. The tubing fits within the recesses of the system’s valve blocks, eliminating challenges in manual installation. The RS 10 system also includes pressure and flow sensors, as well as optional pH, conductivity, and dual wave-length ultraviolet (UV) sensors. The sensors enable several control methods for filter dynamics. The system also includes an air sensor to switch automatically from fed-batch to batch mode when a feed solution has run out.

Measurement Accuracy: Repligen also offers the line of KrosFlo RPM systems integrated with the FlowVPX in-line variable–path-length spectrophotometer. These systems enable in-line protein concentration management, controlling filtration processes with real-time insights. By leveraging in-line concentration data, users can analyze measurements without performing up-front calculations or overcompensating for variability. Such analyses help users to understand their processes while reducing cycling times and batch risks. The system offers live concentration control by taking 12 quality-control–grade concentration measurements every minute. In some applications, the concentration can range from 0.1 to 300 mg/mL without necessitating off-line sampling or dilution. Those concentration measurements enable the system software to adjust automatically to the correct path-length range, ensuring measurement accuracy. The instrument can take readings at multiple wavelengths with field-swappable light sources.

TFF processes typically use vessel volume as the main parameter for starting, ending, and transitioning between steps. Such volumes represent an estimation of the actual concentration and thus can differ significantly from the actual product concentration. Taking off-line samples to verify concentration can be tedious and reduce product viability as product recirculates through the pump. The increased accuracy reduces processing time, decreases product exposure to shear force, and enhances process reproducibility.

Automation and Network Integration: The RS 10 system includes a built-in data historian as well as software for easy network integration and automatic backups for data security. Integration with certain network types also enables remote batch operation.

Questions and Answers

What tubing sizes are compatible with the RS 10 system, and what is its hold-up volume? The RS 10 system uses tubing with an 1/8th-inch inner diameter. The hold-up volume depends on which filters (flat sheet or hollow fiber) and sensors are used but usually falls between 20 and 30 mL.

Are the system’s components single use, or is system cleaning in-place (CIP) required? All components are single use. Using hollow-fiber cartridges enables fully closed processing. Otherwise, the system can automate CIP for flat-sheet cassette applications.

Find the full webinar online at www.bioprocessintl.com/category/webinars.