AAMI ISO 10993-4:2017 pdf download – Biological evaluation of medical devices
6.1 General requirements
IMPORTANT — Since this is a horizontal International Standard, sound rationales can be supplied to justify the choice of test category(ies) based on the device being characterized. For example, in vivo testing for evidence of thrombosis is frequently the preferred method for device characterization in the thrombosis category. However, in some cases, written rationales that include a combination of tests from the categories of coagulation, platelets, haematology and complement can be used as a substitute for thrombosis testing.
6.1.1 Figure 1 illustrates a decision tree that can be used to determine whether testing for interaction with blood is necessary. Blood interactions can be divided into several categories based on the primary process or system being measured. Table 1 lists examples of devices which contact circulating blood and the categories of testing appropriate to each device. The list is not all inclusive and sound judgement shall be applied to devices not listed in the tables. For medical devices where a specific International Standard (vertical standard) exists, the biological evaluation requirements and test methods set forth in that vertical standard shall take precedence over the general requirements suggested in this document.
6.1.2 Where possible, tests shall use an appropriate model or system which simulates the geometry and conditions of contact of the device with blood during clinical applications. The simulation should include an appropriate duration of contact, temperature, sterile condition, anticoagulant (and level; see 6.1.12) and flow conditions. For example, for devices of defined geometry such as a vascular stent, the surface area used in the test, in cm 2 , shall be given consideration relative to the fluid volume of the in vitro test system. For devices with undefined or complicated geometry (such as a dispersion of PVA particles used as an embolization agent), mass should be used instead of surface area to determine the amount of sample used in test system.
Only direct or indirect blood-contacting parts should be tested. The selected test methods and parameters should be in accordance with the current state of the art. Appropriate type and level of anticoagulant may be case specific depending on both the device use indication and the type of test conducted. Include information on the specific type and level of anticoagulation used and provide a discussion on the ability to discern positive and negative responses. For further information, see 6.1.6 and C.2 for animal studies, 6.1.12 for in vivo and ex vivo tests, 6.3.1 for in vitro tests and A.3 for catheters and guide wires. As many tests for haemocompatibility are recognized to be strictly surface-contact dependent, such tests (e.g. complement activation) will not apply to indirect contact applications.
6.1.3 Controls (positive and negative) shall be used unless their omission can be justified. Where possible, testing should include a relevant predicate device already in clinical use (i.e. a LMCD) or a well-characterized material [6] . Controls should include negative and positive reference materials. All materials and LMCDs tested shall meet all quality control and quality assurance specifications of the manufacturer and test laboratory. All materials and devices tested shall be identified as to source, manufacturer, grade and type.