What is Biocompatibility and Why Does it Matter?

Biocompatibility is the ability of a medical device to perform its intended function without causing a harmful local or systemic response in the patient. All devices that contact the body — directly or indirectly, transiently or for extended periods — must be assessed for biocompatibility. ISO 10993-1 establishes the overall framework for biological evaluation, guiding manufacturers through which tests are appropriate for their specific device based on contact type, duration, and nature. Under EU MDR and virtually every major regulatory framework globally, a complete biocompatibility evaluation following ISO 10993-1 is a General Safety and Performance Requirement.

What Changed in ISO 10993-1:2025?

The 2025 edition of ISO 10993-1 introduces several important updates: (1) Stronger emphasis on a risk-based approach — chemical characterisation and toxicological risk assessment (TRA) are now more prominently positioned as tools that can reduce or replace animal testing, (2) Updated guidance on the biological evaluation plan and biological evaluation report structure, (3) Clearer requirements for documenting the rationale for waiving specific tests, (4) Enhanced focus on extractables and leachables analysis as a prerequisite for TRA, (5) Updated guidance on equivalence assessments for devices using materials identical or similar to well-characterised existing devices. Manufacturers should review their existing biological evaluation reports against the 2025 requirements.

The ISO 10993 Series: Which Parts Apply to Your Device?

ISO 10993 comprises 22 parts covering different aspects of biocompatibility. The most relevant for most manufacturers include: ISO 10993-1 (overall evaluation framework), ISO 10993-3 (genotoxicity, carcinogenicity, reproductive toxicity), ISO 10993-4 (haemocompatibility), ISO 10993-5 (cytotoxicity), ISO 10993-6 (local effects after implantation), ISO 10993-10 (sensitisation and skin irritation), ISO 10993-12 (sample preparation and reference materials), ISO 10993-17 (toxicological risk assessment), ISO 10993-18 (chemical characterisation). The selection of applicable parts depends on device contact type (surface, external communicating, implant), contact duration (limited <24h, prolonged 24h–30d, permanent >30d), and the nature of the body contact.

Chemical Characterisation: The New First Step

Under the 2025 version of ISO 10993-1, chemical characterisation (ISO 10993-18) is positioned as a primary first step in the biological evaluation process. Chemical characterisation identifies and quantifies all chemical substances that may be released from the device — through extraction studies and analytical chemistry (GC-MS, LC-MS, ICP-MS). Once chemical constituents are identified and their potential extractable levels quantified, a Toxicological Risk Assessment (TRA) can determine whether their concentrations pose any biological risk — potentially eliminating the need for certain in vivo animal tests. This approach is both more scientifically rigorous and more animal-welfare-sensitive than traditional battery testing.

Common Biocompatibility Testing Gaps Identified by Notified Bodies

The most frequently cited biocompatibility deficiencies in MDR technical file reviews include: (1) Use of outdated ISO 10993-1:2009 or earlier editions without assessment against the 2018/2025 requirements, (2) Missing chemical characterisation for devices with patient contact — particularly polymers, adhesives, and coatings, (3) Incomplete toxicological risk assessment — listing hazard data without quantitative risk characterisation, (4) Equivalence claims for materials without accessing the comparator device's full chemical composition data, (5) Missing or inadequate haemocompatibility testing for blood-contacting devices, (6) No update to the biological evaluation report following manufacturing process changes (e.g., sterilisation method changes, material supplier changes).

Practical Steps for Turkish Manufacturers

Turkish medical device manufacturers should: (1) Identify which ISO 10993-1 edition their current biological evaluation was conducted under — if prior to 2018, a gap assessment is essential, (2) Commission a gap analysis of existing biocompatibility data against ISO 10993-1:2025 requirements, (3) Ensure chemical characterisation (ISO 10993-18) has been completed for all patient-contacting materials, (4) Update biological evaluation plans and reports to reflect current standard requirements, (5) Ensure any material or process changes since the last biological evaluation have triggered a review and update of the biocompatibility assessment, (6) For new devices, integrate biocompatibility planning into the design and development phase — not as a post-design afterthought.

Conclusion

Biocompatibility evaluation is not a one-time exercise — it is a living component of the technical file that must be maintained and updated throughout the device life cycle. Turkish manufacturers who invest in up-to-date chemical characterisation, rigorous toxicological risk assessment, and biological evaluation reports aligned with ISO 10993-1:2025 will have a significantly smoother MDR certification experience and a stronger defence against post-market safety questions.