Advantages of Single-Use Chromatography Systems for Downstream Processing

Young researcher working with chemical samples in laboratory with HPLC system and chromatography equipment | Image Credit: © BGStock72 – Stock.Adobe.com

Chromatography is an essential unit operation during downstream processing of many biopharmaceuticals. Traditional stainless-steel, multi-use systems require extensive cleaning and cleaning validation between each use, which adds time and cost to the overall manufacturing process. Use of disposable systems for upstream processing has become widespread for R&D, clinical, and commercial operations, and interest has steadily increased in downstream applications, including chromatography. Single-use (SU) chromatography systems offer manufacturers of biologic drug substances numerous benefits.

Several key components

While commercially available SU chromatography systems differ in many ways, they generally consist of a similar set of key components serving specific, needed functions. The main elements are the system hardware and a disposable flowpath, according to Samantha Sbardella, head of integrated platform solutions at MilliporeSigma, the life science business of Merck KGaA, Darmstadt, Germany.

At the heart of the system is a framework that houses the essential components and automation software and facilitates the management and control of system operations. A separate framework contains the SU flowpath, which is a single-use assembly containing the prepacked column. A separate area contains the pumps necessary to circulate the mobile phase through the system. Pre-column and post-column instrumentation include the analytics needed to evaluate the process fluid being loaded on the column and the eluate coming off the column. Devices are also included to remove air bubbles from the liquids as they are loaded on the column and flow meters for monitoring the flow rate of the mobile phase. “These components are included to ensure effective and reliable separation while minimizing contamination risk and facilitating system use and maintenance,” Sbardella says.

Compatible with numerous purification technologies

Disposable chromatography systems available today have advanced sufficiently to enable their use with a wide variety of chromatography technologies beyond traditional affinity, ion-exchange, and size-exclusion resins. Some SU systems, according to Sbardella, are designed to integrate membrane chromatography, which offers advantages such as higher flow rates and reduced buffer consumption compared to traditional resin-based systems, and monolithic columns, which she notes provide high mass transfer rates and low back pressure, making them suitable for high-throughput applications.

In addition, SU systems can be adapted for continuous chromatography operations. For this application, Sbardella observes that the flow paths and system configurations must be specifically designed to support uninterrupted processing.

Suitable for use with many modalities

As with permanent, stainless-steel chromatography systems, SU units can be used to purify a wide variety of biologic drug substances including recombinant proteins, monoclonal antibodies (mAbs) and other antibody-based products, viral vectors, and plasma-derived products.

For recombinant proteins, SU systems offer significant flexibility with reduced risk of contamination and are, Sbardella comments, ideal for processes that require high purity. The ability to quickly switch between different SU assemblies, meanwhile, allows for efficient processing of antibody-based products that often require specific purification steps. “The minimized risk of cross-contamination is crucial in multi-product facilities,” she contends.

For viral vectors used in gene and gene-modified cell therapies, SU chromatography systems facilitate high-throughput processing while reducing the risk of contamination and ensuring product safety, according to Sbardella. Elimination of the need for extensive cleaning between batches is also advantageous for maintaining the integrity of sensitive biomolecules, such as plasma-derived products, she says.

Widely applicable

In addition to being compatible with many types of chromatographic media and biologic modalities, SU systems find use across the drug-development cycle, including clinical and commercial operations, by a wide variety of end users. “Single-use chromatography is particularly attractive for manufacturers looking to reduce the clean-area classification, mitigate contamination risks, facilitate modular facility designs and increase speed-to-market for closed-processing applications,” Sbardella states.

That includes many different types of drug developers. Companies focused on biologics, such as mAbs, recombinant proteins, and vaccines, can leverage SU systems for their flexibility, reduced contamination risk, and ease of use, Sbardella notes. Small to mid-sized developers with limited resources for extensive cleaning and validation processes can, meanwhile, benefit from the simplicity of SU systems, allowing them to focus on innovation and product development, she says. For contract manufacturers serving multiple customers, SU systems help streamline operations while minimizing cross-contamination risks, adds Sbardella.

The ability to handle sensitive materials while ensuring high purity and safety is attractive to viral-vector manufactures, according to Sbardella, while the quick turnaround times and flexibility of SU chromatography systems are ideal for vaccine manufactures facing rapid development and production cycles, especially during health crises. SU chromatography systems are also well-suited for use by developers of personalized medicines, which often require adaptable and scalable solutions for processes tailored to individual patient needs, she observes.

It is important to recognize though, Sbardella emphasizes, the benefits of traditional, stainless-steel, multi-use systems for high-volume, repetitive production needs. “The decision to employ single-use systems often depends on the specific operational requirements, scale of production, and strategic goals of the organization,” she concludes.

Considerable benefits

Use of disposable chromatography systems provides many benefits across these numerous applications. Given their SU flowpaths and closed-processing solutions, they are ideally suited to multi-product processes, according to Sbardella. As importantly, the systems on the market today deliver high accuracy gradients and can address challenging high-resolution separations, she adds. Some also have in-line dilution capabilities, which reduces their footprints while increasing their flexibility.

Overall, the key benefits of single-use chromatography systems as highlighted include reduced contamination risk, simplified cleaning and maintenance for faster turnaround times, the potential for lower overall costs due to reduced labor needs and increased efficiency, greater flexibility and scalability, reduction of hold-up volumes leading to improved productivity, enhanced safety, reduced likelihood of human errors during processing due to automation and user-friendly interfaces, and simplification of validation processes for greater assurance of regulatory compliance.

A few barriers to adoption

Realizing the many benefits of SU chromatography systems does require overcoming some hurdles to implementation of this technology. Initially, in fact, the focus within the industry on high-volume products often limited the use of disposable chromatography, according to Sbardella. “There is a current trend, however,” she observes, “toward the development of drug products that target smaller patient populations and/or are highly potent and require much lower doses for which GMP [good manufacturing practice] manufacturing scales are reduced and can support the use of disposable equipment.”

Companies looking to implement SU chromatography systems for purification of biologic drug substances must, therefore, be prepared to face and overcome a number of possible barriers to adoption. Ensuring that disposable systems meet all regulatory requirements for safety and efficacy can also be challenging, particularly for modalities at nascent stages.

Companies that lack experience with SU technologies must expect to go through a learning curve associated with the operation and integration of these systems into existing workflows, according to Sbardella. That often includes changes to operational procedures, staff training, and potentially the redesign of facilities, which can represent a significant undertaking. She also notes that ensuring candidates are compatible with disposable chromatography technologies and evaluating whether their specific purification needs can be effectively met with SU systems is essential as well.

General concerns about supply-chain reliability, performance limitations, and environmental issues can also act as barriers to adoption of disposable chromatography systems. “The need to rely on external suppliers for SU components, the potential for scalability issues with high-volume or complex purification processes, and issues around the disposal of SU materials are all considerations related to operational sustainability that must be addressed when deciding between single-use and multi-use systems. Careful thought must be given to the specific needs and capabilities of each organization and the benefits and challenges associated with SU chromatography systems [should] be thoroughly evaluated,” Sbardella believes.

Opportunities for improvement

While single-use chromatography systems offer several advantages, there are aspects that could benefit from improvement. Enhancing cost-effectiveness through reduced prices for single-use components or offering more flexible pricing models could reduce upfront investment costs and make these systems more accessible, particularly for smaller manufacturers or startups, according to Sbardella. Improving the reliability and predictability of supply chains, including faster lead times and better inventory management, would, meanwhile, enhance operational continuity, she says.

Improving the integration capabilities of SU systems with existing equipment and processes would also facilitate smoother transitions and reduce operational disruptions. That includes, says Sbardella, better integration with data analytics and cloud-based solutions for enhanced data-management capabilities, particularly improved process monitoring, control, and reporting, which would allow for more informed decision-making and greater process optimization.

Finally, Sbardella would also like to see the development of clearer performance metrics for SU chromatography systems, particularly in terms of scalability and reproducibility. “Standardizing performance benchmarks could help users better evaluate system capabilities and make informed decisions,” she contends.

Important takeaways

Single-use chromatography systems have gained significant traction in the biopharmaceutical industry due to their ability to reduce contamination risks, simplify the validation process, and streamline operations, especially in environments where multiple products are processed, according to Sbardella. In addition, SU system suppliers stay abreast of regulatory developments and design their systems to meet stringent regulatory requirements and ensure product quality and safety. Advances in technology have, furthermore, resulted in disposable chromatography systems with the flexibility to efficiently support both small-scale clinical trials and large-scale commercial manufacturing, Sbardella says.

Indeed, continuous advances in technology, including improvements in materials, automation, and integration with data management systems, are enhancing the performance and capabilities of SU chromatography systems, contends Sbardella. Manufacturers also often provide training programs to ensure that operators are well-equipped to handle the technology effectively.

Finally, Sbardella notes that, as the industry becomes more aware of environmental issues, there is a growing focus on developing sustainable practices, including exploring biodegradable materials and recycling options for single-use components. “Understanding these aspects can help stakeholders in the biopharmaceutical industry make informed decisions regarding the implementation and utilization of SU chromatography systems in their processes,” she concludes.

The overall result of these various advances and efforts in combination with increasing demand for biologics, personalized medicine, and more efficient manufacturing processes, concludes Sbardella, will lead to significant growth of the market for SU chromatography systems, creating opportunities for both investment and further innovation in the sector.

About the author

Cynthia A. Challener, PhD, is a contributing editor to BioPharm International®.

Article details

BioPharm International®
Vol. 38, No. 2
March 2025
Pages: 13–15

Citation

When referring to this article, please cite it as Challener, C.A. Advantages of Single-Use Chromatography Systems for Downstream Processing. BioPharm International 2025 38 (2).