All single-use is not created equal – how can you tell the difference?

By Ray Baldwin – Business Development Manager, Watson-Marlow Fluid Technology Solutions (WMFTS)

Single-use systems are becoming more popular in bioprocessing to deliver sterility and protect product integrity. But not all single-use systems are fit for purpose, especially those which were not designed for the specific application for which they are being used. Choosing the right components is vital to ensure contamination is prevented and the system is not compromised, to protect both the manufacturer and patient, and to ensure Good Manufacturing Practice (GMP) requirements are adhered to. 

Benefits of single-use in biopharmaceutical manufacturing

As the industry moves rapidly away from the era of blockbuster drugs, biopharma companies lean towards developing multiple medicines simultaneously to mitigate business risk and enhance chances of commercial success. Processing lines therefore require flexibility and the ability to pivot between different batches while still maintaining the highest levels of sterility and preventing contamination. This is particularly true for Contract Development Manufacturing Organisations (CDMOs) who offer specialised services to multiple pharma customers and therefore must move quickly and efficiently between batches. The growth of the CDMO market is expected to outpace pharma to 2028ⁱ with growing demand for their specialised services, but as competition increases, trust in contamination prevention is vital to their business success.

Single-use systems are so much more flexible than traditional stainless-steel equipment, so it’s easy to see why their popularity continues to grow. But we should not be complacent, there are important factors to consider when choosing a single-use system for the biopharma industry to produce an effective, efficient and safe processing line.

Why aren’t some single-use systems up to scratch?

Behind the times

Many single-use systems were designed to meet 20-year-old specifications, but our understanding of optimal processing parameters, the materials available, and the regulations have significantly changed in this time. While updating the designs might seem an easy solution, any changes must be clearly documented and approved to ensure good change control governance is observed. The validation burden is of particular concern in this highly regulated industry, as falling foul of the regulators can cause delays and additional costs in the development timeline. In order to ease that pain, validation services provided by suppliers help to enable regulatory compliance and give manufacturers confidence in updating their designs to new specifications.

Off label use

Many single-use components offer potential benefits over and above those applications they were originally designed for. This, however, is a double-edged sword. Using components under different conditions than they were validated for, e.g. temperature, pressure and length of time, could lead to compromised quality. For fluid management in particular, maintaining consistent pressures and flow rates is key for consistent production quality and accurate volume control. Running processes for longer, at higher temperatures and pressures, could lead to tubing degrading and potential resulting fluctuations in pressure and flow rate, not to mention risks of compromised integrity and leakage.

A matching set

Peristaltic pumps are ideal for many biopharma applications as their high dispensing accuracies allow precise volumes to be added to bioreactors and final doses. The external motion of the pump can however result in external wear if tubing isn’t specifically designed for this purpose. 

Unlike wine, it doesn’t get better with age!

Within the industry, contamination control is a key component of GMP compliance and a comprehensive contamination control strategy (CCS) is now a requirement of Annex 1.ⁱⁱ Processing often involves high-cost consumables and high value products, some of which are hazardous, so preventing leakage is also necessary to minimise risk and production costs. Designing systems to fully maintain their integrity throughout the system lifetime is therefore a priority.

The chemicals used in biopharma processing can be corrosive, like sodium hydroxide, and over time exposure to these can result in damage to single-use components. Multiple properties affect the durability of a tube, including the material, its resistance to different chemicals, and the thickness. Choice of tubing will therefore determine whether it survives the cycle. This does present an opportunity for single-use. Changing fluid path components between batches allows the line to be optimised for that specific process, without limiting your production capabilities. The length of exposure can also impact degradation, so limiting stationary time with constant flow can help to minimise this.

Understanding extractables and leachables

The risk of wear will not only compromise efficiency and system integrity but, due to the materials used for single-use systems, can also generate contamination from the materials themselves. It is therefore important to consider the function of the system, what fluids and solvents will be used and whether this could result in extractables or leachables from the materials contaminating the drug product. The important question to ask is: Are the materials validated for use in these applications and what specific requirements must be met?

Extractables are compounds that can be extracted from a single-use technology (SUT) under laboratory conditions, using solvents, exposure times, and exposure temperatures that represent reasonable worst-case conditions for most typical biomanufacturing applications.ⁱⁱⁱ

Contamination of the fluid pathway with some chemicals can be harmful if transferred into the drug product. Extractables tests are performed to identify chemicals in the single-use component that have the potential to leach into the fluid pathway.

Extractables are tested following BioPhorum Operational Group (BPOG) guidance, and a new USP standard coming out in May 2026 (USP <665>). Selected solvents are pumped through single-use technologies for between 24 hours and 70 days and tested for the presence of volatile, semi-volatile and non-volatile compounds, as well as elemental impurities.

Results are used to show compliance to the registration, evaluation, authorisation and restriction of chemicals (REACH), the restriction of hazardous substances (RoHS) and the toxic substances control act (TSCA): regulations that control the release toxic substances. Biopharma companies can also use these results to determine whether a supplier’s specific products are suitable for their bioprocess.

Extractables results give a generic understanding of chemicals that might leach into the process to provide an understanding of whether the SUT in question will be process appropriate. 

“Quality is never an accident. It is always the result of intelligent effort.”

John Ruskin

Leachables testing is similar to that for extractables, but is performed to a specific bioprocess, as opposed to being generic. This will include extracting the specific SUT at the process specific temperature, duration and actual product in use. This gives a real world understanding of leachable chemicals in a process and provides assurance that no toxic chemicals are entering the drug through the SUT. 
 
For final drug manufacture, it is necessary to prove that no toxic chemicals are leached under process conditions. This can be done using a combination of extractables results and a toxicology analysis, however regulators such as the FDA and the EMA often require a leachables study. 

Quality at the expense of efficiency?

With all these considerations to protect the quality of the product, the efficiency of the process can seem like a lower priority. But the cost of developing novel medicines can stretch into the billions, and for biopharma companies, any opportunity to reduce this is a necessity for commercial viability.
 
For organisations with less experience in fluid process design, areas of improved efficiency may be overlooked when prioritising product quality. A biopharm customer had been using a smaller ID tubing for their process, but this did not support optimal levels of suction. By partnering with WMFTS, fluid handling experts were able to recognise the issue and recommend a larger bore tubing option, refining the existing system to deliver enhanced production with only a minor change. Manufacturers are best positioned to build reliable systems by partnering with an expert that is well-versed in the niche requirements of this industry and can make recommendations to improve the system.

Continuous manufacturing – Biopharma’s holy grail? 

As with most industries, biopharma is constantly looking for ways to make medicines more efficiently. Continuous bioprocessing is a possible solution that has been much lorded as the future of the industry. Other industries have been using this approach for decades but biopharma has been relatively slow in its adoption, due the exceptional regulatory demands and precise control of processing parameters required. However, the shift is underway and many organisations are already reaping the benefits. 

The growth of continuous bioprocessing has led to an increase in processing cycles of up to 90 days. For those employing single-use systems, design engineers must play close attention to the functional life of each component. Some of these systems will have been designed for hours or days, not months! Flexible tubing must therefore demonstrate confidence that it will deliver long life under typical process conditions for continuous bioprocessing. It should also deliver a consistent flow rate over the duration of the production cycle to maintain product consistency and quality. 

Preparing for the future

It is impossible to know what the requirements of future processing systems will be. This fast-paced industry continues to innovate and develop novel treatment modalities and development methodologies that could completely alter the face of biopharma in the future. As we’ve seen with the rise of biologic therapies, the demands of these may require completely new processing systems. These advances are accompanied by increased regulatory demands to protect quality and patient safety, all of which combine to make future-proofing a processing line seem impossible.

Single-use systems can be easily updated with new components to meet new requirements, making them a good choice for both present and future requirements. However, supply of these components should also be considered. With recent supply chain disruptions still fresh in the industry’s mind, working with a global partner that offers a reliable supply chain will help to minimise the impact of future industry supply issues.

So, how should you plan your single-use system?

Taking all of these factors on board can seem daunting, but the upfront effort will pay off with reliable, effective and efficient processing systems that deliver high quality products. Start by understanding the needs of your system and the end-goal, and bioprocess specialists will design a system that delivers long-term savings without being swayed by the promise of cheaper solutions in the short term. 

Bespoke validation you can trust

In order to support the enhanced validation demands from regulators, Watson-Marlow Fluid Technology Solutions validation team apply their expertise to create tailored validation packages. The team design bespoke validation studies using the most up-to-date, industry-recognised standards alongside fully qualified testing partners. These assessments incorporate rigorous testing and data analysis to ensure tat each specific quality assurance requirement is met, supported by decades of expertise in biopharmaceutical equipment manufacturing. 

Features and benefits

• Complete confidence in product quality
• Designed to reduce your validation burden
• Tailored validation packages to meet your specific needs
• Product quality assurance with 10-6 SAL (sterility assurance level)

About the author

Ray Baldwin is Global Business Development Manager for Single Use Technologies at Watson-Marlow Fluid Technology Solutions (WMFTS). Since graduating from Northumbria University with a degree in Manufacturing Systems in 1997, Ray has worked at HyClone, Sartorius, SAFC Biosciences and ASI and now brings his wealth of single-use experience to WMFTS.