Biological Evaluation
of Medical Devices

The biological evaluation of medical devices is a structured process aimed at demonstrating the biological safety of a device in relation to its intended use, the materials used, and the duration and nature of contact with the human body.

According to

Regolamento (UE) 2017/745 MDR and the ISO 10993 series, biological evaluation must be integrated into the medical device risk management process and supported by scientific evidence, experimental data, and toxicological assessments.

The objective is to identify, assess, and control potential biological risks associated with the device, ensuring regulatory compliance and maintaining the safety and performance requirements necessary for CE marking.

TentaConsult Italia supports medical companies in the planning, management, and preparation of the documentation required for the biological evaluation and biocompatibility assessment of medical devices.

Biological evaluation must be performed in compliance with the requirements of Regulation (EU) 2017/745 (MDR) and the applicable standards of the ISO 10993 series, with particular reference to:

• ISO 10993-1 — Biological evaluation within the risk management process
• ISO 10993-17 — Toxicological risk assessment
• ISO 10993-18 — Chemical characterization of materials
• ISO 14971 — Risk management for medical devices

The process includes:

• Analysis of the device’s intended use
• Medical device categorization
• Biocompatibility assessment
• Evaluation of available data
• Identification of documentation and testing gaps
• Chemical characterization strategy
• Integration of literature data, testing results, and existing evaluations
• Overall biological safety assessment

Compliance with ISO 10993 is a central element of MDR technical documentation and enables manufacturers to demonstrate the biological safety of the device throughout its entire lifecycle.

Definition of the Biological Evaluation Strategy

The Biological Evaluation Plan (BEP) is the strategic document that defines the methodological approach to the biological evaluation of a medical device.

The BEP includes:

• Definition of the biological evaluation strategy
• Identification of applicable biocompatibility endpoints
• Evaluation of materials and components
• Assessment of biological contact
• Definition of the chemical characterization strategy
• Gap analysis of available data
• Identification of any additional testing requirements

Proper preparation of the BEP enables a structured approach to biological compliance, reducing regulatory issues and requests for additional information from Notified Bodies.

Final Assessment of Biological Safety

The Biological Evaluation Report (BER) collects and integrates all the evidence needed to demonstrate the biological safety of a medical device.

The BER may include:

• Integration of available data
• Analysis of scientific literature
• Evaluation of biocompatibility testing
• Integration of toxicological assessments
• Overall analysis of biological risks
• Conclusions on the biological safety of the device

The document represents one of the fundamental elements of MDR technical documentation and must be consistent with the technical file, the risk management process, and the product’s regulatory strategy.

Toxicological Assessment According to ISO 10993-17

The Toxicological Risk Assessment (TRA) is a key activity for identifying and evaluating the toxicological risks associated with materials, components, and substances that may be released from a medical device.

The toxicological assessment may include:

• Scientific literature review
• Analysis of available toxicological data
• Assessment of CMR and ED substances
• Evaluation of systemic exposure
• Calculation of margins of safety
• ADME assessments
• Analysis of extractables and leachables (E&L)

The TRA supports the demonstration of the biological safety of the device and contributes to compliance with the requirements of the MDR and ISO 10993-17.

Biocompatibility is one of the essential requirements for demonstrating that a medical device can be used safely without causing unacceptable biological effects.

The biocompatibility assessment must consider:

• Device type
• Materials used
• Nature and duration of contact
• Manufacturing processes
• Sterilization
• Available experimental data
• Clinical and literature evidence

The approach must be risk-based and documented in accordance with the requirements of ISO 10993 and Regulation (EU) 2017/745 (MDR).

Identification of Documentation and Testing Gaps

Gap analysis enables the identification of potential deficiencies in technical documentation, available biological data, or the regulatory compliance strategy.

The activity may include:

• Review of existing documentation
• Verification of compliance with ISO 10993 standards
• Identification of missing endpoints
• Assessment of the need for additional testing
• Definition of regulatory priorities
• Strategic support for MDR compliance

A structured approach helps reduce delays in the CE marking process and improve the robustness of technical documentation.