Safety risk categorization for organic extractables and manufacturing aid constituents
Medical matters has developed a risk management (RM) tool that allows to calculate risk scores for chemical constituents. Risk scores are based amongst others on a constituent’s physicochemical properties and its quantitative structure-activity relationship (QSAR) assessment outcomes. Risk scores therefore reflect the patient safety risk posed by a detected leachable/extractable or any other constituent, by consideration of the following two factors: the hazard presented by a compound (reflecting its toxic potential) and the likelihood that a patient would be exposed to sufficient
REACH and MDR hazardous substances
REACH is the abbreviation for ‘Registration, Evaluation and Authorization of Chemicals’. It is an EU regulation that requires manufacturers and importers to register all chemicals produced or imported in significant quantities in the European community. If the portfolio of a medical devices manufacturer includes an article with an identified hazardous substance above the 0.1% (w/w) limit that originates from the REACH candidate list, the information and notification obligations of the REACH regulation are relevant for these articles. Updates to the
Probabilistic derivation of population thresholds for human skin sensitizer
Reynolds et al. has introduced the concept of a population threshold for human skin sensitizers – a chemical-specific exposure level at which no individual in a population will experience induction of contact allergy to a chemical. Therefore, a Bayesian multilevel (hierarchical) regression model was developed to estimate population thresholds under the conditions of a human-repeat-insult-patch-test. The modelling-based skin allergy risk assessment approach was then used to estimate the population thresholds for 30 sensitizers using a weight-of-evidence across publicly available human,
QMS: Entanglement of biological safety and hazardous substance assessments
The compliance of medical devices with hazardous substance regulations and ensuring their biological safety are entangled tasks. At Medical Matters, biological safety and hazardous substance assessments are therefore strongly interlinked. If the portfolio of a medical devices manufacturer includes an article with an identified hazardous substance above the 0.1% (w/w) MDR limit, regulatory obligations get relevant for these articles. Moreover, as hazardous substance source lists are updated regularly, source lists should be monitored for new entries to ensure continued compliance
Quantitative acceptance criteria for chemical equivalency testing
Chemical equivalency testing can be used to assess the biocompatibility impact of changes on final finished devices. However, one drawback of this approach is the lack of acceptance criteria for determining if two sets of extractables data are effectively equivalent. To address this gap David M. Saylor and Joshua A. Young have published an article in Journal of regulatory toxicology and pharmacology in which they propose a statistically motivated approach to evaluate the outcomes of chemical equivalence testing for specific chemical constituents
Weight-of-evidence implementation for biocompatibility assessments
Biocompatibility Evaluation; Biological safety assessment. Regulatory guidances for biological safety describe biocompatibility evaluations of medical devices as a risk-based approach. However, they do not provide specific guidance on how to incorporating a holistic review of all the available data into a risk assessment. One of the major factors contributing to the difficulty of reviewing biocompatibility evaluations for market approval is that biological assessments include several conservative worst-case assumptions and exaggerated exposure scenarios. These are supposed to prevent a potential underestimation of risk. On the