The Differing Stability Testing Strategies in Medical and Combination Devices

Design validation testing, for safety and performance, is required for traditional single use devices (e.g. dressings or catheters) and for combination devices, but there can be significant differences in the approaches to testing. One area where this applies is stability studies.

Recent regulations for single use devices, such as the MDR and ISO 11607:2019, contain obligations for real time (natural ageing) stability studies, which are supported by accelerated ageing validation (whilst waiting for the passage of time). The testing required after ageing is generally restricted to maintenance of sterility and a repeat of any quality assurance work carried out in production. The accelerated ageing for these products usually follows the philosophy of ASTM F 1980 Standard Guide for Accelerated Ageing of Sterile Medical Device Packages. A range of temperatures can be used for the accelerated ageing with the most common being 55°C and 65°C, if an acceleration factor of 2 is used. The rate of physical and chemical changes is expected to double for every 10°C increase in temperature.

However, the approach for combination devices can be quite different. Whilst ever increasing temperatures should increase the rate of decay of a product, there comes a point at which the heat will drive a change not normally seen in ambient storage (in plastic devices, for instance, embrittlement, softening, or charring). In the case of biologics denaturing of the active ingredient will occur well below 55°C. For this reason these products are often stored and transported at 2°C to 8°C, whilst single use devices can be stored in less tightly controlled warehousing. The shelf life validation temperatures for combination devices normally follow the advice given in the International Committee for Harmonisation Guidelines (ICH Q1A (R2) Stability testing of new drug substances and drug products) with a typical elevated temperature being 25°C. Humidity control is also required by ICH though not by ASTM.

The frequency of testing also varies according to the device application. For the dressing we would typically test moisture vapour transmission, absorbency, package strength, package integrity, and other properties at the outset and then again after 1, 3 and 5 years equivalents. For pharmaceutical products the shelf life is shorter but the frequency of testing higher. In this case, performance and dose accuracy testing has to be supplemented by testing of chemical changes, such as ingredient stability and drug device interactions. 

In conclusion, the needs of stability testing are unique to every product and need expert advise in order to design the best test programme, a service that the experts at MET are happy to provide.