Tangential Flow Filtration 101 — The Tech, The Need, And The Market

By Shalini Nagar, Research Nester

In fields like biochemistry, immunology, and microbiology, the separation and purification of biological materials play crucial roles in driving innovation forward. This is because isolating and purifying biological materials enables us to understand their properties better, which can lead to the identification of potential therapeutic targets, the development of diagnostic tests, and the creation of new medications.

As a result, tangential flow filtration (TFF) becomes essential. TFF is a technique utilized for separating and purifying proteins and other biological molecules from mixtures like cell culture media or lysates. It allows researchers in biochemistry, immunology, and microbiology to remove impurities while retaining the desired molecules — an invaluable tool. The fluid is carried through the filter parallel to it, as opposed to being forced through a membrane perpendicularly, which can clog the filter media, as is the case with other filtering systems. The remainder, the retentate, is recycled back to the feed while the permeate — particles that pass through the membrane — are set aside. This approach provides consistent filtration and repeatable results.

Types Of TFF

1. Microfiltration – Microfiltration is a process where suspended solids are removed from the fluid by means of microporous media. The pore size of the membrane ranges from 0.1 to 1 micron. Unlike reverse osmosis or nanofiltration, the membrane does not need to be pressurized. As a pretreatment to reverse osmosis or as an individual filtration technique, it is routinely applied for this purpose. Membrane microfiltration is expected to garner revenue of $1.8 billion by the end of 2030. These filters are porous, which enables water to be passed through them for the purpose of removing biological matter, dissolved solids, small colloids, bacteria, and turbidity. Microfiltration has various applications such as cold sterilization of beverages and pharmaceutical products, use in the dairy industry, separation of bacteria from water, oil and water separation, etc.
2. Ultrafiltration – Ultrafiltration (UF) is a membrane filtration technique similar to reverse osmosis that uses the pressure of hydrostatics to push water through an ultrasonic permeable membrane. Ultrafiltration membranes usually have a pore size of 103 to 106 Daltons. In order to produce water with very high purity and low silt density, UF is a pressure-driven barrier to suspended solids, bacteria, viruses, endotoxins, and other pathogens. Ultrafiltration has various benefits such as no need for chemicals, simple automation, environmentally friendly, and a small process and plant footprint.

Advantages Of TFF

1. No filter cake – In tangential flow filtrations, the sample flows and rinses the membrane surface, which reduces concentration polarization from flow rate reduction and prevents the deposition of macromolecules. As a result, it guarantees a constant flow rate and greatly increases the filter membrane's lifespan. A large volume can be processed utilizing an ideal membrane surface area because the transmembrane pressure is also established and sustained.
2. Gentle separation – TFF separates sensitive biomolecules gently and with little shear stress because it acts at low transmembrane pressure.
3. Concentration and diafiltration – Additionally, during tangential flow filtration, the permeate that penetrates the membrane is collected, while the leftover fluid is recycled and concentrated, allowing for the exchange of buffers (diafiltration).
4. Linear scale-up – TFF systems are compact in nature and able to add more modules or increase the length of hollow fiber modules, allowing for flexibility when expanding the filtration area. Most TFFs are linearly scalable because of this.
5. Reusable – TFF devices may be used again with correct cleaning and storage, thereby reducing the cost of consumables by more than 80% compared to a normal filtration flow.

Disadvantages Of TFF

Complexity: TFF systems are difficult to set up and operate as compared to flow filtration, requiring additional tools such as holders, pumps, pressure sensors, etc.

Applications Of TFF

1. Viral vector – TFF is used in viral vector manufacturing for two major purposes: defiltration and volume reduction before the capture chromatography stage. Prior to the last sterile filtering, the final concentration is exchanged to the formulation buffer.
2. Bioprocess – TFF is used in all stages of a bioprocess, including clarifying, chromatography, concentration, and diafiltration steps as well as final product filtration. Therefore, it is crucial to maximize the effectiveness and speed of TFF unit operations.
3. Vaccine purification – The type of cells involved, the characteristics of the virus, and the characteristics of the process fluids all influence the clarifying approach choice. Since single-use technologies are being used more often upstream, filtration-based technologies such as TFF have become more important in the clarification of vaccines.

Market Overview

The tangential flow filtration industry is positioned to experience growth in the upcoming years. As per a report by Research Nester, the global market size for TFF is anticipated to surpass $15 billion by the conclusion of 2035 with a compound annual growth rate (CAGR) of 16.20% between 2023 and 2035. In 2022, the TFF industry’s market size was $3 billion due to the growing demand for biopharmaceuticals and extensive research and development in the pharmaceutical sector. With the market expansion, more companies are expected to join the industry, leading to heightened competition and price reductions. Furthermore, as companies advance their technologies and processes for efficiency, they can deliver higher-quality products in less time, thereby lowering prices. The market is also experiencing growth due to the increasing requirement for purifying biomolecules, like proteins, nucleic acids, and viruses.

The TFF testing market is segmented by product into systems, membrane filters, and accessories. Among these, membrane filters are expected to hold the largest segment share. Membrane filters play a vital role in the separation of solid particles from liquid solutions. These filters are widely employed in the pharmaceutical industry for the purpose of flow filtration. This process significantly cuts down on drug manufacturing expenses by eliminating undesired components from solutions.

By material – The market is segmented into polyether sulfone (PS), polyvinylidene difluoride (PVDF), and regenerated cellulose. Among these, PS is widely utilized for its affordability, versatility, and ability to withstand most chemicals. Its flexibility and chemical resistance make it a perfect option for TFF, enabling the separation and purification of proteins and other molecules. Additionally, its low cost makes it particularly appealing in the pharmaceutical sector.

By application – The market is segmented into bioprocess, viral vector, and vaccine purification. Among these, the bioprocess segment is expected to hold the largest market share. Bioprocessing plays a crucial role in producing recombinant therapeutic proteins, monoclonal antibodies, and various other biologics. It relies on TFF as a means to separate proteins and molecules from solutions.

By technique – The TFF market is divided into ultrafiltration and microfiltration. The ultrafiltration segment is expected to hold the largest share, 38%, by the end of 2035. Tangential flow filtration employing ultrafiltration is widely utilized in the pharma sector to separate proteins, viruses, and various particles from aqueous solutions. This method enables the production of proteins, which is a critical step in the advancement of pharmaceuticals.

Industry Trends To Watch

Based on current industry trends and advancements, the TFF market is expected to continue its growth trajectory in the coming years. Here are a few industry trends to watch:

• Increasing revenue of cell and gene therapy – Gene therapy is used for treating various diseases, such as heart disease, cancer, cystic fibrosis, diabetes, hemophilia, and AIDS, for which cases are rising globally. As of 2022, almost 770 of the more than 1,200 ongoing clinical trials for cell and gene treatments were focused on treating cancer. With the increasing adoption of cell and gene therapy, there is a rising need for tangential flow filtration. This technique is employed to separate elements of biologics, including cells, proteins, and viruses. The growing demand for separators in this field is driving the expansion of the tangential flow filtration market.
• Growing sales of biotech drugs and biologics – TFF is used in biopharmaceutical manufacturing downstream processes to provide fast concentration and defiltration. Therefore, with the rising sales of biotech drugs, the TFF market is anticipated to grow rapidly.
• Rising prevalence of various diseases – It is estimated that more than 877,500 Americans die every year due to heart disease or stroke, accounting for nearly one-third of all deaths. With the technological advancements in the field of biotechnology, it is anticipated that a minimum of 45% of the current global disease burden can be addressed using biological development. As technology advances, there is growing awareness and better management of various diseases. Consequently, there is a demand for tangential flow filtration systems to effectively purify and handle the fluids utilized in medical treatments.

Key Players In The Tangential Flow Filtration Market

Merck KGaA

Merck is one of the major key players in the tangential flow filtration market. The company launched a new Continuum Platform in order to manufacture advanced biotherapeutic drugs such as Tangential flow filtration systems, membranes, and accessories.

ABEC, INC.

ABEC introduced its specialized tangential flow filtration (TFF) systems in September 2021. These systems were designed to improve efficiency in processes for bioprocessing customers thereby boosting both product range and revenue, for the company.

Sartorius AG

A major player in the biotech industry, specializing in filtration, fermentation, and laboratory technologies. In April of 2020 Sartorius made a purchase of assets, from Danaher’s life sciences division. These assets consisted of chromatography hardware, industrial skids, resins and use tangential flow filtration (TFF) systems. This strategic move allowed Sartorius to broaden their range of products and reach out to customers.

Pall Corporation

Pall Corporation, a company specializing in filtration and separation across industries, including biopharmaceuticals introduced the Minimate EVO TFF system in July 2021. This system aims to streamline laboratory scale processes such, as concentration, desalination and buffer exchange workflows.

Synder Filtration, Inc.

Synder Filtration recently introduced the OptimaFlow Series elements, which, for all currently used standard and MAX membrane types for ultrafiltration and microfiltration, are accessible in the same standard element sizes and models. On demand, custom models are offered.

About the Author:

Shalini Nagar is a writer at Research Nester Pvt. Ltd.