Irritation Assessment of PVC-based Polymers with a Reconstructed Human Epidermal Model
In 1959, Russel and Burch published The Principles of Humane Experimental Technique, which introduced the 3R approach to replace, reduce, and refine testing performed on animal models. This approach has resulted in a movement towards the development of new analytical approaches (NAMs) that implement in vitro, in silico, and in chemico techniques to assess biological endpoints in place of animal models.
Internationally, governing bodies are transitioning to the encouragement of in vitro tests over in vivo, with this 3R approach in mind. While the FDA has not fully adopted in vitro over in vivo models for medical device biocompatibility testing, it is stated that a secondary purpose of the ISO 10993 standards is to “utilize scientific advances in our understanding of basic mechanisms, to minimize the number and exposure of test animals by giving preference to in vitro models in situations where these methods yield equally relevant information to that obtained from in vivo models.”
The three primary biocompatibility tests all medical devices are required to undergo for FDA biological risk evaluations are cytotoxicity, irritation, and sensitization. Unlike the standard cytotoxicity test, which is performed on an in vitro culture of mammalian cells, the sensitization and irritation tests are typically performed on animal models such as guinea pigs and rabbits. For the intracutaneous reactivity irritation test, extracts collected from the medical device are injected into the subcutaneous tissue of a rabbit; the injection sites are then assessed for observable changes such as erythema, edema, or necrosis.
This test often requires a large quantity of medical devices to undergo extraction to obtain the minimum volume of treatment necessary, and may require a 1-2 month turnaround time in addition to the financial and ethical costs of the test. These expenditures increase if, upon completion of the test, the device is found to be irritating, which would require the manufacturer to reassess their product’s composition, processing, and manufacturing environment, followed by retesting. With proper screening techniques, a medical device manufacturer can be confident in their product’s biocompatibility prior to initiating these tests that are costly economically, ethically, and on production timelines.
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