ISO 10993-18:2020 is the standard FDA recognizes for chemical characterization of medical device materials, and the framework built into it is the opposite of how most teams still scope a biological evaluation. The default is not to run the standard battery of biological assays and characterize chemistry as a supplement. The default is chemistry first — identify and quantify what the device actually releases, run it through a toxicological risk assessment, and reserve biological testing for whatever that combination genuinely cannot answer.
The stepwise framework ISO 10993-18 actually specifies
The standard does not ask for a single extractables report. It builds the chemical characterization up in stages, and each stage narrows what still needs biological testing wrapped around it. Skipping a stage — going straight to extraction without first nailing down material selection and configuration — is the most common way a chemical characterization report comes back incomplete.
- Device configuration. What the device is actually made of and how the materials are arranged — the starting point every later stage depends on.
- Material composition. Identification and quantification of the chemical constituents in each material of construction.
- Manufacturing-introduced substances. Mold release agents, process contaminants, and sterilization residues — chemistry the nominal material specification never mentions.
- Degradation products, where relevant. For absorbable or degradable materials, the chemistry the device becomes over its intended use, not just the chemistry it starts as.
Why the AET has to be set before the extraction study, not after
The analytical evaluation threshold is not a lab-reporting convenience. It has to be derived from a toxicologically valid value, documented, and agreed before the extraction study is run — because the AET determines what counts as a finding. Set it after the data comes back and the choice stops being a scientific judgment; it becomes a decision shaped by whatever number makes the results look clean. ISO 10993-18:2020's Amendment 1, published in 2022, went further and specified how to determine the uncertainty factor the AET calculation depends on, tightening a step labs had previously handled inconsistently.
The AET is not the number the lab reports at the end. It is the decision that determines which numbers the lab is even allowed to call a finding — and it has to be made before anyone sees the data. Why the AET is set first, not last
When chemistry can stand in for a biological assay
FDA's current guidance on the use of ISO 10993-1 — first issued September 2020 and updated September 8, 2023 — keeps the same underlying logic even as it has added detail, including new coverage for devices in intact-skin contact. Chemical characterization, combined with a toxicological risk assessment that can account for every constituent identified above the AET, can address certain biocompatibility endpoints without a corresponding biological assay. That substitution only holds where the chemistry is complete and the TRA is defensible; a chemical characterization report with gaps does not earn a waiver, it earns a request for the missing data. This is also where the analysis has to reconcile with the risk file it feeds — a TRA conclusion that never makes it into the risk management file does not protect the submission.
- Characterize configuration and materials first. Establish what the device is actually made of before scoping any extraction study.
- Set the AET before extraction runs. Derive it from a toxicologically valid value and document it in advance.
- Run the TRA against every constituent above the AET. Let the toxicological risk assessment decide what the chemistry does and does not already answer.
- Order biological testing only for the remaining gap. Reserve assays for what chemistry and the TRA cannot adequately address, not as a parallel default.
None of this changes what biocompatibility ultimately has to demonstrate. It changes the order of operations, and the order is where most biological evaluation plans lose time and money — running assays first and characterizing chemistry as an afterthought, then discovering the chemistry raises questions the biological data cannot answer either. Scoping the chemical characterization and the AET before design controls lock the material selection is the point where a chemistry-first plan is still cheap to build.
Frequently asked questions
Can chemical characterization replace biological testing?
For some endpoints, yes — when the chemical characterization is combined with a toxicological risk assessment (TRA) that can account for every identified and quantified constituent. Where the chemistry and the TRA already answer the risk question, ordering the biological assay anyway adds cost and animal use without adding information. Where they cannot — because a constituent cannot be identified, or its toxicology is not adequately characterized — biological testing fills that specific gap.
What is the analytical evaluation threshold (AET)?
The AET is the concentration above which an extractable or leachable chemical must be identified and reported. ISO 10993-18 sets out how to calculate it from a toxicologically valid threshold, and it has to be derived, documented, and agreed before the extraction study runs — not chosen afterward to fit whatever the lab happened to find.
Does FDA require ISO 10993-18:2020 specifically?
ISO 10993-18:2020 is the chemical characterization standard FDA recognizes in its current biocompatibility guidance on the use of ISO 10993-1, most recently updated September 8, 2023. Data developed against the earlier 2005 version of ISO 10993-18 typically needs a gap analysis against the 2020 version before a reviewer will rely on it.
Sources & further reading
- ISO. ISO 10993-18:2020 Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process. iso.org
- FDA. Use of International Standard ISO 10993-1 — Guidance for Industry and FDA Staff. fda.gov
- Federal Register. Use of International Standard ISO 10993-1 — Guidance for Industry and FDA Staff; Availability (88 FR 62091, Sept. 8, 2023). federalregister.gov
This article is provided for general informational purposes and reflects the regulatory landscape as of September 2026. It is not legal or regulatory advice. Confirm current ISO and FDA requirements with the agency, ISO, or qualified counsel before acting.
