PFAS in Medical Devices: What ISO 10993‑18 Won’t Catch

A single example in ISO 10993-1:2025 is the tip of a much larger problem — and standard analytical screening will likely miss it entirely.

When ISO 10993-1:2025 was published, most of the industry’s attention landed on contact duration calculations and the updated biocompatibility evaluation framework. Understandably so. But tucked into clause 6.4.3.3 is something that deserves its own conversation: the explicit callout of PFHpA (perfluoroheptanoic acid, CAS 375-85-9) — a per- and polyfluoroalkyl substance — as a chemical of concern in medical devices.

One substance named in one clause might seem like a narrow compliance checkbox. It isn’t. PFHpA is a marker for a much broader class of chemicals that are persistent, potentially toxic at low concentrations, and analytically invisible to the standard testing most teams default to.

What PFAS Are — and Why They’re Everywhere

PFAS stands for per- and polyfluoroalkyl substances — a class of several thousand synthetic chemicals defined by carbon-fluorine bonds that are among the strongest in organic chemistry. That bond strength is precisely what makes PFAS so useful in industrial and medical applications: it presents chemical resistance, thermal stability, low friction, and non-stick properties. It’s also what makes PFAS persistent in the environment and in biological systems. These compounds don’t break down. They accumulate.

In medical devices, PFAS enter the supply chain through several routes that aren’t always obvious or disclosed:

•        Fluoropolymer components — PTFE, FEP, PVDF, and related materials used in tubing, catheters, seals, and coatings

•        Processing aids — PFAS-based surfactants and release agents used during manufacture that may remain as residuals in finished components

•        Supplier non-disclosure — PFAS may be present in sub-components or raw materials without appearing on any SDS or material declaration, particularly when used as processing aids below reporting thresholds

The supplier non-disclosure issue is particularly significant for regulatory purposes. A material may be legitimately labeled fluoropolymer-free while still containing PFAS residuals from upstream processing. Your chemical characterization strategy needs to account for this.

The Toxicological Concern

PFAS accumulate in biological tissues — particularly the liver, kidney, thyroid, and immune system — and do not clear readily. Regulatory toxicology bodies in the US and EU have been progressively tightening permissible exposure thresholds as the evidence base has grown. Margins of safety for PFAS exposures from medical devices are increasingly narrow, especially for devices with prolonged or permanent contact and for patient populations with repeated exposures.

PFHpA specifically was flagged in ISO 10993-1:2025 because of its bioaccumulation concern,  it has demonstrated toxicological concern at low concentrations and because it represents a pattern: as longer-chain PFAS have been phased out under regulatory pressure, industry has shifted toward shorter-chain alternatives — including PFHpA — that were initially assumed to be safer. That assumption is now under active scientific and regulatory scrutiny.

The regulatory trajectory for PFAS is clearly toward restriction, not accommodation. Identifying and documenting PFAS in your device now — before a guideline tightens or a regulatory body issues new requirements — is a substantially better position than discovering them during a submission review.

The Analytical Gap: Why Standard Screening Fails

This is the part that catches teams off guard, and it’s worth being direct about it.

ISO 10993-18 standard chemical characterization screening will not detect PFAS.

The standard analytical approach — typically a universal semi-quantitative scan to detect a wide range potential extractables — is not designed to capture highly polar, low-volatility fluorinated compounds at the very low concentrations of regulatory concern. The low toxicological limits of PFAS require a fundamentally different analytical strategy:

•        LC-MS/MS — targeted and quantitative liquid chromatography coupled with tandem mass spectrometry, capable of detecting individual PFAS compounds with high specificity

•        Detection limits in the ng/L range — standard extractables screening typically operates at µg/L or higher; PFAS thresholds of concern may fall well below that

•        Total Oxidizable Precursor (TOP) assay — for detecting PFAS precursors that may not appear as parent compounds but will convert to persistent PFAS in biological systems; critical when processing aids are the suspected source

•        Method-appropriate extraction — aqueous methanol or other polar solvents optimized for fluorinated compounds, not the solvent systems used in standard extractables protocols

The practical implication: if your chemical characterization report was generated using a standard ISO 10993-18 extractables protocol without PFAS-specific additions, it cannot be used to make a statement about PFAS content. The absence of detected PFAS in that report is an artifact of the method, not a finding.

What This Means for Your Biological Evaluation

If your device incorporates fluoropolymer materials, uses components sourced from suppliers who may use fluorinated processing aids, or contacts patients for prolonged or permanent durations, PFAS should be an active consideration in your chemical characterization planning — not a gap to be explained away.

For new submissions: Consider whether your chemical characterization plan explicitly addresses PFAS. If your device has risk factors for PFAS exposure, the absence of PFAS-specific testing is a gap that a thorough reviewer may surface.

For legacy submissions: The update to ISO 10993-1:2025 and the explicit PFHpA callout create a reasonable basis for regulators to ask whether older biological evaluations remain current. If you’re planning updates for other reasons, this is worth folding in.

For supply chain management: Material declarations and SDS review are not sufficient to rule out PFAS from processing aids. Consider adding explicit PFAS disclosure requirements to supplier questionnaires and qualification processes.

KEY REGULATORY REFERENCE

FDA’s partial recognition of ISO 10993-1:2025 (recognized with caveats, not in full) means that the PFHpA callout in clause 6.4.3.3 is part of a standard the agency has formally engaged with. Teams planning Q-Subs or pre-submissions on biological evaluation strategy should be prepared to address PFAS if their device has relevant materials.

The Bottom Line

ISO 10993-1:2025’s callout of PFHpA is not a standalone compliance item — it’s a signal that the regulatory framework for PFAS in medical devices is active and evolving. The analytical challenge is real: you cannot rely on standard ISO 10993-18 screening to give you the answer. PFAS require targeted methods, appropriate detection limits, and in some cases a TOP assay to capture precursor compounds.

The teams that will be best positioned are those who address this proactively — understanding where fluorinated materials appear in their device and supply chain, and ensuring their chemical characterization strategy is actually capable of detecting the chemicals of concern being asked about.

Sandi Schaible is Founder & President of Bonded in Science LLC and an expert member of ISO TC194 WG1 and WG14.