ANSI AAMI ISO 10993-12:2012 pdf download – Biological evaluation of medical devices
5.2 Certification of RMs for biological safety testing
5.2.1 Qualification of an RM is a procedure that establishes the numerical or qualitative value of the biological response of the material under specified test conditions, ensuring reproducibility of the response within and/or between laboratories. The range of biological responses associated with the material shall be established through laboratory tests. NOTE See also ISO Guide 34.
5.2.2 Suppliers of RMs shall certify the materials. The supplier determines the extent of chemical and physical characterization that is performed. The individual laboratories that use the RM shall identify the biological characterization necessary to qualify a RM for a specific test or procedure. Commercially available materials may be used as RM, provided they are certified and qualified.
5.2.3 Certification of a RM is a procedure that establishes the numerical or qualitative value of the biological response of the material under the specified test conditions. This process serves to validate the testing of the material for that particular response and results in the issuance of a certificate. The biological response of the material shall be established through interlaboratory tests.
6 Use of RMs as experimental controls
6.1 RMs or CRMs shall be used in biological tests as control materials to demonstrate the suitability of a procedure to yield a reproducible response, i.e. positive and/or negative. Any material used in this way shall be characterized with each biological test procedure for which the use of the material is desired. A material characterized and then certified for one reference test method or response, e.g. delayed-type hypersensitivity, shall not be used as an RM for another, e.g. cytotoxicity, without additional validation. NOTE The use of an RM will facilitate the comparability of the response between laboratories and help assess reproducibility of the test performance within individual laboratories. For comparison of the biological response, it is desirable to use RMs having a range of responses, e.g. minimum, intermediate or severe.
6.2 RMs used as experimental controls shall meet the established quality assurance procedures of the manufacturer and test laboratory. They shall be identified in relation to source, manufacturer, grade and type. RMs are processed as described in Clause 8.
6.3 When RMs are used as experimental controls, they shall be in the same material class as the test sample, i.e. polymer, ceramic, metal, colloid, etc. However, pure chemicals may be used as experimental controls for mechanistically-based test procedures， e.g. genotoxicity and immune delayed-type hypersensitivity assays.
8.2 Test samples from devices not required to be sterile in use shall be used as supplied and handled aseptically throughout the test sample preparation. If sterile test samples are required for a test procedure, e.g. for cytotoxicity testing, the effect of the sterilization or resterilization process on the test sample and RM shall be considered.
8.3 When test samples and RMs need to be cut into pieces, as described in 10.3.3, the influence of previously unexposed surfaces, e.g. lumens or cut surfaces, shall be considered. Tools used for cutting medical devices into representative portions for testing shall be cleaned between uses to prevent contamination.