ANSI AAMI ISO 10993-12-2012 pdf download
ANSI AAMI ISO 10993-12-2012 pdf download.Biological evaluation of medical devices
5.1 General
Reference materials (RMs) are established by individual laboratories. The extent of chemical, physical and biological characterization is determined by the individual laboratory. Commercially available articles may be used as reference materials. NOTE 1 See also ISO Guide 35. Certified reference materials (CRMs) are selected for their high purity, critical characteristics, suitability for the intended purpose and general availability. The critical chemical, physical and biological characteristics shall be determined by collaborative testing in three or more laboratories, and made available to the investigator by the distributor. NOTE 2 It is desirable for users to obtain a commitment from suppliers of RMs or CRMs that these materials will be available to the user for at least five years. A second, but less desirable, option is for the source of the RM or CRM to publish an “open formulation” for the material, i.e., publication of the source materials and details of the processing needed to ensure uniform batches of the RM.
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 RMs shall identify the biological characterization necessary to qualify an RM for a specific test or procedure. Commercially available materials may be used as RMs provided they are certified and qualified.
5.2.3 Certification of an 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, such as either 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 Use of an RM will facilitate the comparability of the response between laboratories and assist in assessing reproducibility of 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 as 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.
7 Test sample selection
7.1 Testing shall be performed on the final product, or representative samples from the final products or materials processed in the same manner as the final product (see ISO 1 0993-1 ) or on appropriate extracts of any of these. The choice of test sample shall be justified. NOTE In the case of materials that cure in-situ, different test samples representative of the cured material versus the uncured state of the material might be needed.
7.2 The same test sample selection procedure applies when an extract is required.
