ISO 10993-12:2021 pdf download – Biological evaluation of medical devices — Part 12: Sample preparation and reference materials
ISO 10993-12:2021 pdf download – Biological evaluation of medical devices — Part 12: Sample preparation and reference materials.
NOTE The use of an kM will facilitate the comparability of the response between laboratories and help assess reproducibility of the test perlornsance 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.
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. However, pure chemicals may be used as experimental controls for mechanistically-based test procedures, for example, genotoxicity and immune delayed- type hypersensitivity assays.
7 Test sample selection
Testing shall be performed on the final product, representative samples from the final product, materials processed in the same manner as the final product see ISO 10993.1), 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 sEtu, different test samples representative of the cured material versus the uncured state of the niaterial might be needed,
For absorbable materials that could potentially have toxic degradants and residuals, testing of intermediate products should be considered.
The same test sample selection procedure applies when an extract is required.
8 Test sample and RM preparation
Test samples and RMs shall be handled with care to prevent contamination. Any residue from the manufacturing processes, intentional or unintentional additives or contaminants, shall be considered integral to the medical device, medical device portion or component, or representative sample.
NOTE For additional guidance on preparation, see Annex B
— Test samples from sterilized medical devices and RMs shall he handled aseptically, ii appropriate to the test procedure.
— Test samples which are clean, sterile and disinfected, shall be processed by the method recommended by the manufacturer and handled aseptically, If appropriate to the test procedure.
— The influence of the cleaning process and cleaning agent shall be considered in the selection and handling of the test sample.
Test samples from medical devices not required to be sterile in use shall he 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 kM shall he considered.
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. Furthermore, care shall be taken that the tool itself doesn’t contaminate the device.
9 Selection of representative portions from a medical device
9.1 If a medical device cannot be tested as a whole, each individual material in the final product that is required to be tested shall be represented proportionally In the test sample.
— The test sample of the medical devices with surface coatings shall include both the coating material and the substrate, even if the substrate has no tissue contact.
— The test sample shall include a representative portion of the loint or seal, or both, if adhesives. radiofrequency (RF) seals or solvent seals are used in the manufacture of a portion of the medical device which comes into contact with patients.
9.2 Composite materials shall be tested as finished materials.
9.3 When different materials are present in a single medical device, the potential for synergies and interactions shall be considered in the choice of test sample.
9.4 The test sample shall be chosen to maximize the exposure of the test system to the components of a medical device that arc known to have potential for a biological response.
9.5 Non-patIent contacting portions of the medIcal device should, if possible, be excluded either physically from test sample extracts or by exclusion of the surface area in the calculation of the extraction ratio. When this is not possible, the extraction ratio shall be justified. F.nsure that all contacting portions are covered by the selected extraction vehicle volume.
Clinician and user surface contact with materials other than those In common use In consumer products with a similar nature of contact, should be considered [see ISO 10993-1:2018, 5.2.2, a)J.
9.6 MedIcal device components with different type or duration of tissue contact might need to be extracted and tested separately.