Biological evaluation of medical devices in the EU

Introduction to biological evaluation

Biological evaluation is a part of the verification and validation (V&V) process for medical devices in the European Union. Ensuring that a medical device is biocompatible—meaning it does not cause harmful biological responses—is required for meeting safety and performance requirements under the Medical Device Regulation (MDR) 2017/745.

The biological evaluation process is not just about conducting tests; it follows a scientific risk-based approach that considers the interaction between the medical device and the human body throughout its entire lifecycle. This evaluation must be performed according to ISO 10993-1: Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing and must demonstrate that a device is safe for its intended purpose.

Biological evaluation in the context of verification and validation

Biological evaluation is a verification and validation process, meaning it serves to:

• Verify that the medical device is designed and manufactured in a way that prevents unwanted biological effects.
• Validate that it meets regulatory and safety requirements before market release.

It is closely linked to other design validation processes, such as chemical characterization, toxicological risk assessment, and clinical evaluation, ensuring that the final product is safe for patients and users.

Logic behind the biological evaluation process

The biological evaluation process follows a structured, risk-based approach, ensuring that only necessary tests are conducted, reducing unnecessary animal or human testing whenever possible. The key steps in this process include:

1. Material characterization and risk assessment

Before testing, the manufacturer must gather information on:

• Device composition (materials, coatings, adhesives).
• Manufacturing processes (including sterilization, surface treatments).
• Expected patient contact (duration, frequency, and exposure sites).

This step eliminates unnecessary testing if material safety can be demonstrated through existing data.

2. Determination of biological risks based on ISO 10993-1

ISO 10993-1 provides a decision-making framework for biological evaluation. The standard defines biological endpoints that need to be assessed based on the device’s:

• Nature of body contact (e.g., skin, mucous membrane, blood).
• Duration of contact (e.g., short-term, prolonged, permanent).

3. Biological testing (if required)

If gaps in material safety data exist, the manufacturer conducts biological tests, such as:

• Cytotoxicity (ISO 10993-5) – Evaluates if materials cause cell damage.
• Sensitization (ISO 10993-10) – Identifies allergic reactions.
• Irritation (ISO 10993-10) – Tests for local tissue irritation.
• Systemic toxicity (ISO 10993-11) – Assesses potential toxic effects on organs.

If chemical characterization and existing data are sufficient to demonstrate safety, some tests can be waived, reducing the need for animal studies.

4. Justification of biocompatibility

A biological evaluation report (BER) is compiled, summarizing:

• Data from material characterization.
• Risk assessment findings.
• Testing results (if applicable).
• Rationale for omitting tests (if applicable).

This report must be included in the technical documentation submitted for regulatory approval.

How biological evaluation ensures compliance with MDR

Biological evaluation is a core requirement under MDR 2017/745, Annex I, which mandates that medical devices must not pose unacceptable biological risks.

To comply with MDR, manufacturers must:

• Follow a science-based, risk-driven approach aligned with ISO 10993-1.
• Ensure complete documentation of biological risks and mitigation strategies.
• Justify the selection or omission of tests in the context of intended use.
• Demonstrate long-term biocompatibility, particularly for implantable devices.

Biological evaluation is not just about performing standard tests—it is a logical, structured risk-management process designed to ensure that medical devices are biocompatible, safe, and effective. In the context of verification and validation (V&V), it plays a vital role in proving that devices meet EU MDR requirements.