In biopharmaceutical manufacturing, purification is often the single step that dictates overall production speed. For contract development and manufacturing organizations (CDMOs), emerging biotechs and pharma companies running multiproduct lines, it’s a critical stage where progress could stall.
With downstream processes like purification accounting for as much as 80 percent of total manufacturing costs according to a study published in Frontiers in Microbiology, time lost to unpredictable delays or built-in idle periods can bring significant consequences. Although purification is a required step, the time it takes can be difficult to predict as it depends on product characteristics, batch size, and other variables.
Even without delays, as product moves through final filtration and formulation, equipment and staff often sit idle. There are inefficiencies that cascade through downstream steps, delaying filling, packaging and quality checks. Altogether, the operational drag prolongs critical timelines and erodes competitiveness in a technologically evolving market where speed to patient matters.
Part of a broader industry shift toward agile and scalable manufacturing, newer approaches like single-use and single-pass tangential flow filtration (TFF) are one of the potential methods that biopharma companies can use to overcome these purification bottlenecks.
The benefits of single-use TFF
TFF separates and purifies biological materials by directing the liquid feed stream to move across the surface of a filter membrane instead of forcing it straight through. In this sideways or crossflow movement, smaller molecules slip through the membrane as filtrate, while larger molecules are held back and sent through the loop again. This approach helps prevent build-up on the membrane, so flow stays steady for longer.
Single-use TFF provides the manufacturer with a method of achieving the same aims as conventional TFF, but with an added benefit of having the equipment for one time use.
Accelerated timelines: Traditional TFF systems use complex, reusable assemblies that require manual calibration and thorough cleaning between runs. Such steps require specialized training and extended turnaround times but still carry risk of contamination, which given recent guidance like Annex 1 that focuses on contamination control strategy, can be of concern to regulators. Running multiple therapies on the same equipment demands even stricter contamination measures, which can significantly slow production even further.
Single-use assemblies, by contrast, come ready to use already sterilized and assembled, hence why the changeovers can take hours instead of days. Aside from reducing the contamination risk, it enables process operators to move from one product to the next without the long cleaning cycles typical with traditional systems. With the faster turnaround, manufacturers minimize costly delays. CMC Biologics published an example, where they demonstrated that single-use TFF when utilized for recombinant protein purification reduced both cleaning time and contamination risk.
Operational agility amid workforce constraints: There is a skills gap within biopharma manufacturing in which there is a shortage of skilled manufacturing and quality control experts. This impacts production as it means cleaning and cleaning validation rests on the shoulders of a small number of experienced staff. Downtime is not an option. This in turn slows production and delays product release.
Capability for complex biologics: Single-use TFF enables complex biologics, including fragile molecules in viral vectors, mAbs and mRNA to be purified without risk to the patient. The automation-ready system also allows manufacturers to deliver consistent processes, generate GMP-compliant data on every run and quickly move from process development to full-scale production. At Genentech, fully automated single-use systems with disposable sensors and smart valve control have also reduced operator exposure to high-potency molecules.
The benefits of single-pass TFF
Single-pass TFF utilises a different approach compared to the conventional method. Instead of recirculating product through a membrane loop, it is sent through once, achieving the desired concentration or buffer exchange in a single pass. This reduces residence time, lowers fouling risk and cuts buffer use dramatically compared to traditional diafiltration. Its advantages stand out in three areas:
Efficiency and throughput: Traditional diafiltration consumes large buffer volumes and slows purification. Single-pass eliminates recirculation, cutting buffer needs and boosting flow. When MilliporeSigma applied it to monoclonal antibody purification, they reduced buffer consumption and eased this common bottleneck.
Scalability for high-titer processes: Rising upstream titers often overwhelm downstream capacity, creating a mismatch bottleneck. In a study by Regeneron, they solved this by using single-pass TFF to cut intermediate volumes by half while completely eliminating failure rates.
Continuous processing readiness: Batch processing introduces bottlenecks with every unit operation. However with its linear throughput, TFF single-pass integrates directly into continuous lines, keeping product moving without delays. Automation guided by Process Analytical Technology (PAT) frameworks provides information on critical variables such as transmembrane pressure and protein concentration, enabling long-duration runs to continue without performance drift.
Relieving the bottlenecks
Single-use and single-pass systems solve different pain points in tangential flow filtration:
Single-use TFF is most applicable in multiproduct or small-batch facilities, where sterility and rapid changeovers are critical. It’s especially valuable in clinical-scale production and for emerging therapies, where quick turnaround and contamination control matter more than sheer volume.
Single-pass TFF is most applicable in high-volume or high-titer environments, where buffer use, throughput and scalability are the limiting factors. It can be particularly effective in commercial antibody manufacturing and facilities advancing toward continuous processing.
It may be possible to deploy both systems in order to adapt purification strategies to product type, production scale and facility design.
Where it’s taking hold and where opportunity awaits
Although the core technology has been in place for decades, adoption of single-use is surging in multiproduct facilities, advanced therapy manufacturing and clinical-scale production where speed and contamination control are high priorities. In these settings, many manufacturers are already using single-use TFF to concentrate and diafilter proteins, viral vectors, and other biomolecules. However, there is still room to further accelerate production through newer automation tools and advanced membrane technologies.
Legacy, high-volume, single-product facilities have been slower to adopt newer technologies, largely due to the revalidation efforts required to modify established processes. However, there could be potential operational benefits from applying these products in their manufacturing processes. Single-pass TFF is gaining traction in high-titer antibody production and in continuous bioprocessing paradigm. As facilities evolve, the operational advantages of both single-use and single-pass approaches may become harder to ignore.
Other innovations that extend single-use TFF benefits
In recent years, a wave of supporting technologies are enabling single-use and single-pass TFF applications. The aim of these technologies are to aid the purification process in becoming faster, more dependable and easier to control.
Smarter pumping systems: Today’s digital peristaltic pumps play an integral part of the latest purification equipment, such as TFF systems, allowing precise control of flow accuracy and pressure parameters. Precision is key, particularly with fragile products like monoclonal antibodies or viral vectors, where too much force can shear delicate molecules and too little can bring filtration to a crawl. Live readings from inline sensors also give operators the chance to make informed decisions and verify parameters before the process is compromised.
Membrane technology: Membrane technology has evolved to meet the challenges in modern bioprocessing. New materials capture more product, waste less, and work with a much broader range of biologics.
Process monitoring and automation: Real-time analytics are necessary to flag deviations instantly and streamline processes. At some facilities, fully automated single-use systems use disposable sensors, automated valves, and load-cell monitoring to control pressure and conductivity without manual oversight, improving reproducibility while reducing operator exposure to high-potency molecules.
Continuous integration: In single-pass setups designed for continuous bioprocessing, these same innovations keep product moving without the usual pauses between steps, ensuring stable output over long runs.
Additionally, many facilities are folding these tools into semi- or fully automated production lines. The result is shorter changeovers, fewer manual errors and consistent results.
Evolving toward fully agile manufacturing
The next stage in purification will reshape manufacturing environments to remove bottlenecks before they form.
In a fully agile model, modular suites can be reconfigured for new products or shifting capacity in days rather than months. Purification will be digitally linked to both upstream production and final finishing steps through unified control systems, so product flows continuously from start to finish without delays or manual hand-offs.
Facility-wide data models, supported by PAT and AI, will make production predictive and adaptive, adjusting schedules, equipment allocation and process parameters automatically in response to changes in demand or process conditions. Infrastructure will be built for therapeutic adaptability, capable of pivoting between vastly different product types and scales from monoclonal antibodies to next-generation gene therapies without re-engineering core systems.
Single-use and single-pass TFF are increasingly becoming part of the modern biopharmaceutical purification toolkit. When integrated with advanced automation and real-time analytics within a modular, data-driven framework, these approaches can significantly accelerate downstream processing. In an increasingly competitive landscape, organizations that embrace such innovations are better positioned to bring new therapies to market faster, more efficiently, and at the scale patients need — while those that hesitate risk falling behind.
