The term biocompatibility refers to the interaction between materials (i.e. in medical devices) and hosts (i.e. patients or end users). To be deemed biocompatible, medical devices which are intended to come into contact with the human body must do so without causing adverse biological effects (e.g. irritation, rashes, burns, cancer).
Establishing biocompatibility is a critical part of the medical device regulatory approval process in many jurisdictions. In this post, we discuss the legal requirements for biocompatibility and how manufacturers can use standards to meet these requirements.
Legal requirements for biocompatibility
Biocompatibility is generally a requirement for all devices which come into contact with the human body. The legal basis for medical device biocompatibility in the EU is the General Safety and Performance Requirements (GSPRs).[1] The GSPRs state that all medical devices must be safe when used in accordance with their intended purpose (GSPR 1). To help ensure device safety, manufacturers must establish and implement a risk management system (GSPR 3).
As it relates to biocompatibility, the risk management system should pay particular attention to:
Manufacturers must ensure that any risks arising from the above factors are eliminated or reduced insofar as possible. Protection measures (such as alarms) and safety information (warnings, precautions, etc.) should also be adopted for risks which cannot be eliminated (GSPR 4).
The UK takes a similar approach to medical device biocompatibility under its Essential Requirements (ERs).[2] The ERs overlap with the majority of the GSPRs set out above, with the exception of the risk management system requirement (GSPR 3). However, in practice, the vast majority of manufacturers do implement risk management systems.
In the US, the FDA will similarly assess biocompatibility in the context of safety of devices when reviewing regulatory submissions. In addition to the endpoints specified in the ISO 10993 (see below), the FDA also has additional recommended endpoints.
Biocompatibility standards
The main guidance for medical device biocompatibility is the ISO 10993 family – a series of 23 standards covering topics ranging from degradation products to blood interactions. Within the ISO 10993 family, ISO 10993-1 is the overarching standard for biological evaluation and testing. Biological evaluation is the process for establishing the overall biocompatibility profile of a medical device.
Biological evaluations are generally carried out in four stages:
To help manufacturers select the appropriate endpoints for assessment, ISO 10993-1 categorises devices in terms of both the type of contact (surface, externally communicating or implantable) and duration of contact (limited, prolonged or long term). Based on these two factors, the table in Annex A of ISO 10993-1 tells manufacturers which endpoints they should be testing. For example, a medical device which comes into limited surface level contact with the skin should be tested for chemical characterisation, cytotoxicity, sensitisation and irritation.
The remainder of the ISO 10993 series then provides further detail on how to test each endpoint. ISO 10993-23, for instance, discusses the hierarchy for irritation testing. This standard specifies that the priority should be to carry out in vitro irritation testing (i.e. tests on reconstructed human epidermis models). If this method of testing does not provide sufficient information to support the biological evaluation, further testing may then be carried out on live animals. Finally, providing the irritancy potential for the device has already been established, non-invasive clinical studies may then be carried out on human subjects.
How we can help
Regtik, our healthcare regulatory explorer tool, can help you navigate the legal maze by walking your product through a series of simple questions designed to determine which rules and regulations are applicable. It is able to provide results for various jurisdictions (the US, EU, UK and Australia) in one single assessment and can be used multiple times on different versions of your product.
If you are interested in learning more about Regtik or would like to request a demo, please contact any member of our team or register your interest below.
[1] Annex I, Regulation 2017/745 (the Medical Device Regulation)
[2] Annex I, Directive 93/42/EEC (the Medical Device Directive)