This document describes considerations for the biological evaluation of medical devices that are composed of or contain nanomaterials. In addition, this guidance can also be used for the evaluation of nano-objects generated as products of degradation, wear, or from mechanical treatment processes (e.g. in situ grinding, polishing of medical devices) from (components of) medical devices that are manufactured not using nanomaterials.
This document includes considerations on the:
— characterization of nanomaterials;
— sample preparation for testing of nanomaterials;
— release of nano-objects from medical devices;
— toxicokinetics of nano-objects;
— biological evaluation of nanomaterials;
— presentation of results;
— risk assessment of nanomaterials in the context of medical device evaluation;
— biological evaluation report;
— nanostructures on the surface of a medical device, intentionally generated during the engineering, manufacturing or processing of a medical device.
The following are excluded from this document:
— natural and biological nanomaterials, as long as they have not been engineered, manufactured or processed for use in a medical device;
— intrinsic nanostructures in a bulk material;
— nanostructures on the surface of a medical device, generated as an unintentional by-product during the engineering, manufacturing or processing of a medical device.
NOTE Examples of unintentional nanostructures on the surface of a medical device are extrusion draw lines and machining/tool marks.
This document is intended to provide a general framework and highlights important aspects which need to be considered when assessing the safety of medical devices composed of, containing and/or generating nano-objects. Additionally, the document identifies several common pitfalls and obstacles which have been identified when testing nanomaterials compared to bulk materials or small molecule chemical species. As a technical report (TR), this document represents the current technical knowledge related to nanomaterials. No detailed testing protocols are outlined or provided. This document can serve as a basis for future documents containing detailed protocols with a focus on nanomaterial testing.
