This document specifies the process and requirements for the toxicological risk assessment of medical device constituents. The methods and criteria used to assess whether exposure to a constituent is without appreciable harm are also specified. The toxicological risk assessment can be part of the biological evaluation of the final product, as described in ISO 10993-1. The process described in this document applies to chemical characterization information obtained in line with ISO 10993-18. When a toxicological risk assessment of either the compositional information or analytical chemistry data (e.g. extractable data or leachable data) are required to determine whether the toxicological risks related to the constituents are negligible or tolerable. The process described in this document is not intended to apply to circumstances where the toxicological risk has been estimated by other means, such as: \u2014 constituents, excluding cohort of concern or excluded chemicals, that are present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold (see applicable requirements in ISO 10993-18:2020, Annex E and ISO\/TS 21726); \u2014 a new or changed medical device for which chemical or biological equivalence has been established with an existing biocompatible or clinically established medical device (see applicable requirements in ISO 10993-18:2020, Annex C). The process described in this document is also not applicable to: \u2014 medical device constituents that do not contact the body (e.g. in vitro diagnostics); \u2014 biological risks associated with physical interactions of the medical device with the body (i.e. application of mechanical forces, energy or surface morphology, etc.), provided that the chemical exposure is not changed; \u2014 active pharmaceutical ingredients of device-drug combination products or biologic components of device-biologic combination products as additional regulatory considerations can apply; \u2014 exposure to a particular constituent that arises from sources other than the device, such as food, water or air.<\/p>\n
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| 2<\/td>\n | undefined <\/td>\n<\/tr>\n | ||||||
| 8<\/td>\n | Annex ZA (informative)Relationship between this European Standard and the General Safety and Performance Requirements of Regulation (EU) 2017\/745 aimed to be covered <\/td>\n<\/tr>\n | ||||||
| 12<\/td>\n | Foreword <\/td>\n<\/tr>\n | ||||||
| 14<\/td>\n | Introduction <\/td>\n<\/tr>\n | ||||||
| 15<\/td>\n | 1 Scope 2 Normative references <\/td>\n<\/tr>\n | ||||||
| 16<\/td>\n | 3 Terms and definitions <\/td>\n<\/tr>\n | ||||||
| 21<\/td>\n | 4 Abbreviated terms and symbols <\/td>\n<\/tr>\n | ||||||
| 23<\/td>\n | 5 Toxicological risk assessment within the biological evaluation process 5.1 General 5.1.1 Risk assessment principles 5.1.2 Hazard identification <\/td>\n<\/tr>\n | ||||||
| 24<\/td>\n | 5.1.3 Risk estimation <\/td>\n<\/tr>\n | ||||||
| 26<\/td>\n | 5.2 Toxicological risk assessment process <\/td>\n<\/tr>\n | ||||||
| 28<\/td>\n | 6 Constituent specific toxicological information 6.1 General 6.2 Identification of hazardous constituents 6.2.1 General <\/td>\n<\/tr>\n | ||||||
| 30<\/td>\n | 6.2.2 Application of the toxicological screening limit <\/td>\n<\/tr>\n | ||||||
| 31<\/td>\n | 6.2.3 Identification of human carcinogens or suspected human carcinogens 6.2.4 Selection of the point of departure <\/td>\n<\/tr>\n | ||||||
| 32<\/td>\n | 7 Tolerable contact level, tolerable intake and threshold of toxicological concern 7.1 Derivation of TCL and TI 7.2 Application of TTC <\/td>\n<\/tr>\n | ||||||
| 33<\/td>\n | 8 Exposure dose estimation <\/td>\n<\/tr>\n | ||||||
| 34<\/td>\n | 9 Margin of safety 9.1 General 9.2 Calculating the margin of safety 9.2.1 General <\/td>\n<\/tr>\n | ||||||
| 36<\/td>\n | 9.2.2 Combining MoS values to address additivity of harm <\/td>\n<\/tr>\n | ||||||
| 37<\/td>\n | 10 Toxicological risk acceptance criteria 10.1 General 10.2 Further risk analysis or risk evaluation or risk control <\/td>\n<\/tr>\n | ||||||
| 38<\/td>\n | 11 Reporting requirements <\/td>\n<\/tr>\n | ||||||
| 39<\/td>\n | Annex A (normative) Evaluation of toxicological data quality when selecting a point of departure <\/td>\n<\/tr>\n | ||||||
| 40<\/td>\n | Annex B (normative) Derivation of toxicological screening limits <\/td>\n<\/tr>\n | ||||||
| 47<\/td>\n | Annex C (normative) Derivation of constituent TI or TCL for select endpoints <\/td>\n<\/tr>\n | ||||||
| 55<\/td>\n | Annex D (informative) Typical assumptions for biological parameters <\/td>\n<\/tr>\n | ||||||
| 58<\/td>\n | Annex E (normative) Estimation of an exposure dose <\/td>\n<\/tr>\n | ||||||
| 67<\/td>\n | Annex F (informative) Reporting of toxicological risk assessment information <\/td>\n<\/tr>\n | ||||||
| 72<\/td>\n | Bibliography <\/td>\n<\/tr>\n<\/table>\n","protected":false},"excerpt":{"rendered":" Biological evaluation of medical devices – Toxicological risk assessment of medical device constituents<\/b><\/p>\n |