ISO 10993-12 pdf free download
ISO 10993-12-2021 pdf free download.Biological evaluation of medical devices – Part 12: Sample preparation and reference materials.
4 General requirements
When identifying hazards and estimating risk in relation to medical devices, hazards that arise from changes in the manufacturing process, or insufficient control of the manufacturing process, shall be considered in the design and preparation oftest samples, as described in ISO 14971. Particular attention shall be given to material additives, unintentional base material impurities and manufacturing process residues, e.g. trace elements and cleaning and disinfection agents.
The ISO 10993 series describes many different biological assay systems. Therefore, the individual parts shall be consulted to ascertain whether these are appropriate for specific test systems.
Experimental controls shall be used in biological evaluations carried out in order to either validate a
test procedure or compare the results between materials, or both. Depending on the specifications of a
particular test, either negative controls, blanks or positive controls, or all three, shall be used.
NOTE The same type of control can be applicable to different tests and can allow cross-reference to other established materials and test methods. Additional guidance on the selection of experimental controls is given in Annex A. Use of positive controls for in vivo testing might be affected by animal welfare regulations.
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 distributor.
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 ot 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
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ISO 10993-12:2021(E)
example, delayed-type hypersensitivity, shall not be used as an R M for another, for example, 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.
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.ISO 10993-12 pdf download.
