The Biological evaluation is an essential part of demonstrating the safety of a medical device. The EN ISO 10993 series of standards, which deals with various aspects of the biological evaluation of medical devices, comprises over 20 parts and is relevant to a large number of medical devices.
The new substandard -23 in the context of the EN ISO 10993 series
The MDR’s general safety and performance requirements make it necessary to assess the biological properties of medical devices. For patients as well as users and third parties. This is where the EN ISO 10993 series of standards comes into play, which generally specifies requirements for biological assessments. When it comes to implementation, planning is first necessary. This can then already show that testing according to individual parts of the standard is necessary.
First and foremost is the chemical characterisation according to EN ISO 10993-18, which we have already dealt with in more detail:
Depending on the findings from this test, further tests may be necessary to assess the biological risks.
One finding may be that skin sensitisation and irritation need to be tested. EN ISO 10993-10:2013 has been (and still is) used for this purpose. Since 2020, however, there has been a draft standard of EN ISO 10993-10 dedicated to “skin sensitisation”. This is because the aspect of testing for “irritation” was specifically split off and was published in October 2021 as long-awaited, new standard
It has already been harmonised under the MDR with the Implementing Decision (EU) 2017/745. This sub-standard aims to reduce, refine and replace in vivo test methods for the assessment of skin irritation. It also describes tests using the “RhE model”.
The RhE model according to EN ISO 10993-23:2021 in detail
The tests formulated are intended to predict and classify the irritation potential of medical devices, materials or their extracts in accordance with EN ISO 10993-1. The standard and its test approaches should therefore always be read in the context of the family of standards and on the basis of a test planning taking all aspects into account.
The so-called RhE model is newly introduced. This stands for “reconstructed human epidermis”. The RhE test can replace the in vivo rabbit test established so far according to EN ISO 10993-10, which is used to test for skin irritation during exposure and intracutaneous (intradermal) administration.
Our expert colleague Anne Schopfer from Hohenstein Laboratories can tell us more about the details of the testing:
- RhE models from an internationally established manufacturer of skin models are used
- They consist of normal, human keratinocytes (skin cells)
- These are cultivated on special cell culture inserts and form a multi-layered, highly differentiated model of the human epidermis.
- the skin model is very similar to human skin, making it a useful in vitro tool for assessing skin irritation.
- The test samples are extracted with 0.9% saline (polar) and sesame oil (non-polar) for 24h at 37°C
- The extracts are applied to the skin models and incubated for 18h at 37°C.
- The skin models are then rinsed to remove all remnants of the test pattern.
- The MTT test is used to determine the viability in comparison to the negative control.
- If cell viability is ≤ 50%, the test sample is classified as an irritant substance
- If cell viability is > 50%, the test sample is classified as a non-irritant substance
When the RhE model is not suitable
However, the RhE models are not suitable for all types of irritation tests.
Appendix D therefore lists and describes “Special Irritation Tests”. However, their use requires a justification of the choice of test method. Examples of these special methods are products used in the area of certain mucosal or ocular epithelia. In these cases, the standard recommends considering the use of other in vitro models with relevant cells or tissues if they are suitable for use with medical devices.
In order to check the irritation on the eye, the so-called “rabbit eye test” according to Draize is still used within the framework of EN ISO 10993-10:2013. However, this test has been controversial for years. With the HET-CAM Test („hen’s egg-Test“) as per DB-ALM method Summary n° 96 Hohenstein Medical offers a recognised alternative that is also accredited by the DAkkS.
Are you faced with the task of re-evaluating your medical device with a view to the harmonised standard EN ISO 10993-23? All customer enquiries are handled individually by Hohenstein in order to determine the correct testing and sample preparation and to clarify any questions. Seleon will be happy to support you in the area of compliant documentation in an overall concept. Therefore, please feel free to address your questions to us.
Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.