Discoveries on Applying the New ISO 10993 17 скачать в хорошем качестве

Discoveries on Applying the New ISO 10993 17

In December 2023, FDA recognized the updated standard ISO 10993-17 with very few non-recognized clauses and opened the door to use of a broader toolbox of toxicological risk assessment methods. Since then, practical experience has been gained in applying the new Part 17 standard to various categories of medical devices. Since the updated standard is no longer a one-size-fits-all approach to derivation of allowable limits, certain key principles have been found to be highly effective at achieving favorable outcomes using data sets with complex extractables profiles, involving chemicals associated with different forms of noncancer toxicity or carcinogenicity, and different toxicological mechanisms of action. These principles, which are illustrated by examples from recent toxicological risk assessments, include the application of tiered contact duration (Rd) categories to scale the exposure duration (EEDmax), selection of relevant animal studies to align with the clinical exposure route and duration category, specifying uncertainty factors to align with the minimum exposure extrapolation, and applying release kinetics studies for extraction time points to align with different exposure categories. In addition, other key principles include a judicious approach to summing chemicals within a class or with a common mode of action, a lines-of-evidence based approach to cancer risk calculations, use of professional judgment in adopting a conservative NOAEL that is the highest among several NOAELs but below the lowest LOAEL, and consideration of pathologist findings citing adaptive as opposed to adverse effects when comparing multiple published animal studies for the same substance. These principles, along with properly documented toxicity profiles that meet the data collection requirements stipulated in the new standard, can help ensure best practices, transparency, a favorable margin of safety, and acceptance of the toxicological risk assessment by medical device regulatory agencies.