Single use processing applications

NGP dicussed the limits and benefits of single use processing, and the future direction of this processing paradigm, with Dr. Hélène Pora, Marketing Director, Pall Life Sciences.

NGP. Not all advantages of single use processing are obvious, what extra benefits does this technology offer?

HP. Seemingly unimportant characteristics of single use technologies can add up to significant time and labour savings. For example, single use systems have clear tubing and clear or translucent capsule filter housings, which enable operators to observe fluid levels and flow. This allows fluid discoloration and air pockets to be readily detected, so that problems can be immediately identified and isolated from the rest of the process. Single use technologies can also be supplied pre-assembled and pre-sterilised to significantly reduce setup time.

Reduced capital costs, faster installation and the smaller footprint of single-use systems compared to stainless steel equipment have helped make in-house production feasible for many high-growth biotechnology companies. These same benefits also provide significant cost-savings for large drug companies and contract manufacturers.

NGP. What are the limits in scale of operation?

HP. Single use technologies are now common in full-scale production operations, and range in size from just a few millilitres to several thousand litres. At the uppermost end, disposable bioprocess bags can accommodate up to approximately 3000L of fluid, and disposable bioreactors have been used for production purposes up to 500L of cell culture.

Advances in disposable membrane chromatography are pushing this technology beyond pilot scale applications into commercial production. However, even at commercial scale, single use technologies may have capacity limitations. 3000L bioprocess bags are one example. As non-rigid containers, both their integrity and ability to be handled beyond this size come into question.

NGP. What are the limits of operating pressure and temperature associated with single use systems?

HP. Operating pressure is another area in which single use technologies contrast sharply with stainless steel systems. Single use systems can withstand comparatively less pressure than stainless steel systems. However, exact limits depend on the materials that system components are made of and the tubing attachment method. In general, bioprocess bags and tubing cannot withstand more than a few psi (<0.5 bar) of pressure. However, tubing can be reinforced to withstand greater pressures. Most capsule filters can be used with up to 50 psi (3 bar) pressure, and a limited few can withstand up to 90 psi (6.5 bar) pressure.

Biopharmaceutical manufacturers must consider the temperature limits of single use technologies when selecting new components and systems. Disposable components are generally well-suited for standard biopharmaceutical operating temperatures, which range between four to 40° C. However, some bags, tubing and connectors may not meet low-temperature requirements for storage. While most biopharmaceutical drugs are stored at minus 30° C, some products (e.g. cells) require storage in minus 80° C conditions. It is critical that biopharmaceutical manufacturers validate each component in the assembly to ensure that they meet the complete range of temperature requirements.

NGP. What is the difference between extractables and leachables?

HP. By definition, extractables are potential solutes derived under worst-case conditions from the drug product or process fluid contact materials, typically using model solvents. Leachables comprise, in part, the subset of contact material solutes detectable in actual product or process fluids. Leachables may also be generated through the interaction of products and contact materials over time. Solvent and temperature conditions, among other factors, determine whether extractables or leachables are generated. What is important to remember about extractables is that they represent the potential for soluble materials to leach from the disposable component under extreme testing methods, but would not otherwise be released into the product during normal processing. By contrast, leachables, which are drug product or process fluid-specific, are released into the product under normal processing conditions.

Since leachables pose an inherent contamination threat, the single use industry generally uses the term ‘extractables’ when describing soluble materials that could be released from a disposable component. It is important to note that there will always be some level of extractables present. The goal of extractables testing is not to demonstrate their absence, but rather to make sure that they will not adversely impact the quality, safety or stability of the drug.

NGP. Are there any standards applicable to extractables studies?

HP. While standards for extractables testing do not exist today, the industry is working to establish guidelines for selecting, using and disposing of single-use technologies through the Bio-Process Systems Alliance (BPSA). The goal of BPSA is to globally promote confidence in the application of single-use technologies in the biotech/biopharmaceutical manufacturing industry, and is comprised of leading companies engaged in the manufacture and testing of single-use technologies. There is no doubt that establishing standards for extractables testing is not only an aim of BPSA, but also the end-user biopharmaceutical industry.

BIO

Hélène Pora is Marketing Director with Pall Life Sciences, where she has worldwide responsibility for the development of improved separation and purification solutions for the vaccine and gene therapy market. She also holds global responsibility for the development of improved single use technologies.