The revision of ISO 10993‑1, titled “Biological evaluation of medical devices – Part 1: Requirements and general principles for the evaluation of biological safety within a risk management process”, officially reached final approval (FDIS) as of July 18, 2025 and is now in the final stages of publication, expected in approximately seven weeks. Once published, it will replace the 2018 (5th edition) version.
While this update has cleared the final voting stage, it is not yet published and therefore not formally available. Nonetheless, the approval signals a major shift in approach to biological evaluation of medical devices.
The U.S. FDA currently recognizes ISO 10993‑1:2018, the Fifth Edition issued in August 2018, and references it in its 2023 guidance, “Use of International Standard ISO 10993‑1…” for Premarket submissions (e.g., 510(k), PMA, IDE, De Novo). This guidance explicitly ties biological evaluation to a risk‑management framework using ISO 14971 principles.
As of today, the 2025 edition remains unrecognized by FDA, and industry insiders report that the U.S. delegation voted “No” through each stage of the FDIS process, reflecting FDA force major concerns about implementation. At this time, it is unclear which aspects of the standard will be adopted by the FDA.
ISO 10993‑1 provides the foundational principles and framework for evaluating the biological safety of medical devices in contact, direct or indirect, with patients or users.
The standard:
It’s a core part of material biocompatibility assessment, forming the basis of testing strategies across the ISO 10993 series.
Manufacturers must now estimate biological risk actively, including harm severity and exposure probability. Reasonably foreseeable misuse is explicitly included in exposure scenarios. The biological evaluation becomes a formal part of device risk management rather than a standalone activity.
Novel and complex materials, including nanomaterials, require deeper characterization and chemical data. The standard also adds CMR (carcinogenic, mutagenic, reproductive toxicity) and endocrine disruptor assessment into scope.
Exposure duration is now defined by total days of clinical use, rather than cumulative sessions. This change may result in re‑classification of exposure categories (e.g., prolonged or long‑term use) and trigger more comprehensive hazard testing.
The standard has reorganized sections and introduced new terms: biological hazard, biological harm, biological equivalence, novel material, residual biological risk, etc.
Coverage now includes intermittent contact, animal welfare, and updated evaluation flow diagrams.
Manufacturers should perform a gap analysis comparing existing biocompatibility documentation (per ISO 10993‑1:2018) against the requirements in the approved 2025 version. A new biological evaluation plan will be needed to address any data gaps.
Since the U.S. delegation opposed the FDIS, and FDA has not yet published recognition of the new version, companies should proactively engage with notified bodies or regulators to clarify whether and how 2025 content will be accepted in submissions.
Expect stricter scrutiny of new or complex materials. Risk‑based decision making may reduce reliance on animal testing when robust chemical or in‑silico/in‑vitro data exist, but only if well‑documented and justified.
New exposure categories may shift devices into prolonged or long‑term use brackets, triggering additional testing such as genotoxicity or carcinogenicity evaluations.
ISO 10993‑1:2025 has achieved approval and is in the final publication phase but is not yet published and therefore cannot yet be referenced in regulatory submissions. Once released, it will replace the 2018 edition and introduce notable expansions in risk‑based principles, exposure definitions, material hazard assessments, and toxicological endpoints.
FDA continues to recognize the 2018 edition and has not yet confirmed its acceptance of the 2025 version. Manufacturers should start preparing now: conduct gap analyses, update biological evaluation plans, and engage regulators for clarity.