Biological evaluation of medical devices: strategy, biocompatibility testing and regulatory framework

In the field of medical devices, ensuring patient safety is not only a priority but also a regulatory requirement. Regulation (EU) 2017/745 on medical devices (MDR) sets strict requirements for manufacturers, who must demonstrate both the performance and the biological safety of their products prior to marketing.

In this context, biological evaluation is an essential component of the technical documentation. Its objective is to determine the biocompatibility of the device based on its nature, intended use, and the type and duration of contact with the body.

This process should be approached through a structured and documented methodology, integrated into the product’s risk management. For this purpose, a biological evaluation strategy is defined and documented, scientifically and regulatorily justifying the endpoints considered and the selection (or exclusion) of tests based on the intended use and the type and duration of contact.

What role do in vitro tests play in biological evaluation?

In vitro tests are a fundamental step in the biological evaluation of a medical device. Conducted under controlled conditions, they allow the early identification of potential adverse effects such as cytotoxicity, genotoxicity, irritation, or initial inflammatory responses.

From a regulatory perspective, these tests contribute to a risk-based evaluation strategy by allowing:

• The identification of potential biological risks associated with materials and processes.
• Guidance for decision-making in early development stages (material selection, formulations, processes).
• Support for the technical justification of the evaluation strategy within the technical file.

A well-defined in vitro testing strategy, integrated into the planning of the biological evaluation, helps avoid unnecessary repetition, detect deviations early, and reinforce the consistency of technical documentation. Taken together, this can facilitate regulatory review and reduce the risk of observations due to insufficient justification or evidence.

Regulatory framework for biological evaluation: ISO 10993 and USP <87>

The UNE-EN ISO 10993 series (Biological evaluation of medical devices) provides the international reference framework for the biological evaluation of medical devices. Based on a risk management approach, it sets the criteria for determining which biological endpoints should be assessed according to the type and duration of device contact with the body.

UNE-EN ISO 10993-1 (Evaluation and testing within a risk management process) defines the general principles of this evaluation, including device categorisation and the identification of relevant tests. Within the same series, UNE-EN ISO 10993-5 (In vitro cytotoxicity tests) specifies methods for evaluating cellular responses to extracts or direct contact with the device material. Other parts of the standard address aspects such as irritation, genotoxicity, sensitisation, systemic toxicity, or chemical characterisation.

It is important to note that UNE-EN ISO 10993 does not provide a fixed list of mandatory tests but rather a flexible framework requiring a technical justification tailored to each product. This approach avoids unnecessary testing and reinforces the consistency of the technical file during regulatory reviews.

For manufacturers with international ambitions, particularly targeting the United States market, the United States Pharmacopeia (USP) <87> Biological Reactivity Tests, In Vitro, may also be applicable. This chapter of the USP describes standardised biological reactivity tests focused on cytotoxicity, widely recognised within the US regulatory environment.

Planning and documentation of biological evaluation

Each medical device requires an evaluation adapted to its intended use, as well as the type and duration of contact with the body. Therefore, the biological evaluation strategy must be structured, integrated into risk management, and adequately documented to support the selection (or exclusion) of endpoints and tests.

At AIMPLAS, we support medical device manufacturers and Regulatory and Quality professionals in the design and execution of in vitro tests, in accordance with widely used international standards, including the UNE-EN ISO 10993 series and USP <87>. We also assist in generating the evidence and technical information necessary for integration into the product file.

A rigorous and technically substantiated planning approach ensures dossier consistency and reduces the risk of observations resulting from an insufficiently justified evaluation strategy. Contact us for further information.