BLOG: A More Balanced Understanding Of “Risk”

Earlier this year I was fortunate enough to attend the Disposable Solutions meeting in Munich. A common theme of discussions was the on-going debates around the issues of leachable and extractables and the associated testing standards. This is a topic that has been debated for as long as I have been attending meetings on single use systems, and still seems to be a long way from a consensus between various end users and manufacturing bodies on how to address this issue.

Single use systems have been used for over 30 years in various forms (and much longer in the healthcare systems) and elastomers in various forms for much longer than this. During this period extensive studies have been performed to determine L&E levels for plastic materials used in manufacturing systems. In all of the history of all these studies, the only issue of product recall and failure quoted by regulatory bodies are, as far as I am aware, related to issues with final container closures. However, all meetings on single use systems still seem dominated by this issue.

Regulatory bodies suggest that “risk based approaches” should be taken to assess L&E risks but the approaches proposed by some of the industry groups are tending towards highly extensive testing of all materials and components in a seemingly “no-risk approach”. This approach seems to me to have significant consequences and not just with regards to time and cost. From a supplier perspective, setting the bar so high risks stymying product development and innovation; from an end user perspective it may make manufacturers less likely to switch to single use systems at one level, with serious headaches for those making products that cannot be produced using alternative approaches.

When for example you look at areas like cell and gene therapy products, often produced from multiple biological entities themselves made using entirely single use components, it rapidly becomes apparent that these manufacturing processes will use many hundreds, if not thousands, of single use components. Consequently, increasingly demanding expectations for L&E testing of single use components will be a significant challenge when bringing these types of products forward to market. Achieving compliance could be become very costly and time consuming and potentially delay making these products available to patients. From the position of an “outsider” who is not an expert in this area of L&E testing, I struggle with the proportion and balance relating to patient risk given to this subject compared to others associated with the manufacture of new therapeutics from biological systems, with or without single use systems. How tangible are the risks from L&Es and how close we are to the point of failure, are areas that have not always been well articulated.