AAMI ISO 10993-11:2017 pdf download – Biological evaluation of medical devices
4.1 General
Before a decision to perform a systemic toxicity test is made, ISO 10993-1 shall be taken into account. The decision to perform a test shall be justified on the basis of an assessment of the risk of systemic toxicity. Selection of the appropriate test(s) for a device shall be in accordance with ISO 10993-1, giving due consideration to mode and duration of contact. Testing shall be performed on the final product and/or representative component samples of the final product and/or materials. Test samples shall reflect the conditions under which the device is normally manufactured and processed. If deviations are necessary, they shall be recorded in the test report, together with their justification. For hazard identification purposes, it may be necessary to exaggerate exposure to the test samples. Physical and chemical properties of the test sample including, for example, pH, stability, viscosity, osmolality, buffering capacity, solubility and sterility, are some factors to consider when designing the study. When animal tests are considered, all reasonably and practically available replacement, reduction and refinement alternatives should be identified and implemented to satisfy the provisions of ISO 10993-2. For in vivo acute toxicity testing, in vitro cytotoxicity data are useful in estimating starting doses.
4.2 Selection of animal species
There is no absolute criterion for selecting a particular animal species for systemic toxicity testing of medical devices. However, the species used shall be scientifically justified and in line with the provisions of ISO 10993-2. For acute oral, intravenous, dermal and inhalation studies of medical devices the rodent (mouse or rat) is preferred with the option of the rabbit (lagomorph) in the case of dermal and implantation studies. Other non-rodent species may also need to be considered for testing, recognizing that a number of factors might dictate the number or choice of species for study. It is preferred that a single animal species and strain are used when a series of systemic toxicity studies of different durations are performed, e.g. acute, subacute, subchronic and/or chronic systemic toxicity. This controls the variability between species and strains and facilitates an evaluation related solely to study duration. Should multiple species or strains be used, justification for their selection shall be documented.
4.3 Animal status
Generally, healthy purpose-bred young adult animals of known origin and with defined microbiological health status should be used. At the commencement of the study, the weight variation of animals used within a sex should not exceed ±20 % of the mean weight. When females are used, they should be nulliparous and non-pregnant. Animal selection shall be justified.
4.4 Animal care and husbandry
Care and handling of animals shall conform to accepted animal husbandry guidelines. Animals shall be acclimatized to the laboratory conditions prior to treatment and the period of time documented. Control of environmental conditions and proper animal care techniques are necessary for meaningful results. Dietary constituents and bedding materials that are known to produce or influence toxicity should be properly characterized and their potential to influence test results taken into account.