14 Apr 2025
Christopher Parker, Associate Director and SME Medical Devices
Stephen Doherty, Analytical Chemistry Head
Question
“My device is a cream that’s applied repeatedly during the healing process of a partial-thickness wound. Based on previous experience, I expect there to be some positive responses seen in some of the biocompatibility tests like implantation, but would it be best to use a comparative product as a control in the implant instead of HDPE or saline?"
Answer
In the upcoming revision of ISO 10993-6, a comparative control is the preferred control for all implantation testing. The regeneration of tissue in a wound bed is a delicate process that can be potentially inhibited by a medical device. In order to best qualify the response, comparison against a comparative control is best. It is ideal to perform a wound healing study in which the test device can be applied in a clinical manner to truly understand the tissue response and not only can the effect on the healing response be evaluated, but so can implantation endpoints to 10993-6. If a wound study is not being performed, and implantation needs to be assessed using a traditional 10993-6 model, then a comparative control should be used. Any materials that may absorb/degrade over time, or materials with geometry that isn’t a nice, smooth rod such as a mesh, will likely show a more active and potentially different type of local tissue reaction than a standard HDPE 1 mm x 10 mm rod or an injection of saline.
A comparative control allows a pathologist to better characterize the reaction present as well as determine whether the reaction is adverse. For a cream-type material, the comparative control should have a similar component “recipe” and material list, absorption profile and clinical use or at least be as close as possible. There are instances in which a comparative material will be difficult to determine, such as when the test device is novel or has a different concentration of a particular ingredient. However, in general, when considering chemical composition, try to identify a control with compound concentrations at least as high as those found in your device so safety margins are accounted.