Biological evaluation of medical devices

A new approach to biological safety

ISO 10993-1:2018 is a tool for manufacturers to evaluate and prove biological safety. However, an important shift will take place in 2025. The upcoming version, ISO 10993-1:2025, builds on the paradigm introduced in 2018: a risk-based biological evaluation in line with ISO 14971:2019. The focus is shifting further from standardized testing to the evaluation of relevant biological effects using existing data and stricter requirements for the evaluation of toxicological risks through chemical characterization.

At the same time, there are higher demands for biological evaluation to be clinically relevant and to take place throughout the product's life cycle, including changes, repeated use, and degradation. For manufacturers, this means a need for proactive planning, structured documentation, and expertise in how the standard should be interpreted and applied.

Common pitfalls

Many manufacturers underestimate the importance of biological evaluation. Common mistakes include:

• Unstructured or incomplete biological evaluation plans (BEPs)
• Lack of connection between biological evaluation and risk management, supplier assessment, and clinical evaluation
• Neglect of market-specific requirements (e.g., FDA guidelines)
• Insufficient competence of the team responsible for the evaluation

This often results in data gaps, delays, and, in the worst case, useless test results with consequences for regulatory status and time-to-market.

When should biological safety be evaluated?

Biological safety needs to be evaluated in the following circumstances:

• Medical devices in the development phase: when the product's materials come into direct or indirect contact with intact or damaged skin, intact or damaged mucous membranes, or blood.
• Modified medical devices: when a change is made that affects parts of a product that come (or could come) into contact with intact or damaged skin, intact or damaged mucous membranes, or blood.

A strategic way forward

Successfully navigating the new landscape requires a well-thought-out, risk-based, and regulatory-integrated strategy:

1. Start with the product's life cycle: Biological evaluation must cover the entire useful life of the product, from development to disposal, including any modifications.
2. Develop a clear Biological Evaluation Plan (BEP): The plan should be integrated into the product's overall risk management (ISO 14971) and cover relevant biological effects, data gaps, and testing strategies in accordance with ISO 10993-1.
3. Supplement with Biological Risk Assessment (BRA): A separate biological risk assessment can help focus on new risks, materials, and exposure situations.
4. Have a strong clinical perspective: Tests and methods should be clinically relevant and not just regulatory compliant.
5. Ensure the right expertise: Evaluations must be carried out by trained and experienced specialists. The level of expertise should be documented.
6. Encourage cross-functional communication: Effective collaboration between biocompatibility experts, the biological evaluation team, and other relevant functions throughout the product lifecycle is essential.

Global regulatory differences to keep an eye on

In addition to complying with ISO 10993-1, manufacturers need to adapt their strategy to different regulatory contexts (non-exhaustive list):

• USA (FDA): Has its own guidelines, which are binding in practice. Biological evaluation is required for PMA, HDE, IDE, 510(k) and de novo applications.
• EU: ISO 10993-1:2018 is harmonized and can be used to demonstrate compliance with MDR 2017/745.
• China: Own biocompatibility standard and requirements for type testing by accredited laboratories.

The future: Higher demands – but also greater opportunities

ISO 10993-1:2025 introduces clearer requirements for the evaluation of genotoxicity and carcinogenicity, new categorizations for body contact, and a strengthened role for chemical analysis as the basis for toxicological risk assessments. At the same time, clearer guidance is expected to minimize animal testing and increase clinical relevance. For manufacturers who act proactively and strategically, this opens up opportunities to improve quality, efficiency, and regulatory preparedness.

Skills that take you forward

As a manufacturer of medical devices, do you need help planning, implementing, and documenting biological evaluation in line with current and future requirements? Our experts are here to help. Whether you need to develop a BEP, BER, or BRA, offer support in regulatory strategy, or build internal expertise, we can assist your business in strengthening your capabilities and shortening the path to market.