ISO 10993-12:2021 pdf free download.Biological evaluation of medical devices – Part 12: Sample preparation and reference materials.
5 Reference materials (RMs)
5.1 General
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 RMs.
NOTE See also ISO Guide 35.
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 d 1st rib u to r.
It is desirable for users to obtain a commitment from suppliers of RMs or CRMs stating 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
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 either within laboratories or between laboratories, or both. The range of biological responses associated with the material shall be established through laboratory tests.
NOTE See also ISO 17034.
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 an RM for a specific test or procedure. Commercially available materials may be used as RMs, provided they are certified and qualified.
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
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 or negative, or both. 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, for example, delayed-type hypersensitivity, shall not be used as an RM for another, for example, cytotoxicity,without additional validation.ISO 10993-12 pdf download.