Stakeholders: FDA should align pulse oximeter guidance with updated ISO standard

Stakeholders want the US Food and Drug Administration (FDA) to align its guidance more closely with a pulse oximetry standard being developed by the International Organization for Standardization (ISO) and provide a rationale for increasing its sample size requirement for clinical performance testing.

After reports that many pulse oximeters on the market give inaccurate readings for users with darker skin tones, FDA published a draft guidance in January, which recommends that sponsors provide more data that better reflects the intended patient population and ensure the product labels clearly state their limitations. The proposed guidance has received feedback from more than 50 stakeholders, including medtech lobby groups AdvaMed and the Medical Device Manufacturers Association (MDMA). (RELATED: Pulse Oximeters: FDA drafts guidance to address performance disparities, Regulatory Focus 8 January 2025)

While the draft guidance often references ISO standards, including ISO 80601-2-61, which is currently being updated, both AdvaMed and MDMA argue that the FDA’s recommendations deviate from the referenced ISO standards.

AdvaMed said that FDA has increased clinical testing expectations without sufficient rationale, which is inconsistent with its least burdensome approach and goes against international standards. The group said the agency should rely on international voluntary consensus standards that allow sponsors to align their products across regulatory regimes.

“These standards are developed through an open, inclusive process that ensures balanced participation from various stakeholders,” said AdvaMed. “This process includes due process, opportunities for appeals, and ultimately leads to consensus among globally recognized scientists and regulators in the field.”

“We strongly encourage FDA to continue its active participation in the voluntary consensus standardization process for updating ISO 80601-2-61, and to fully adopt the updated version of this standard once it is finalized,” the group added. “Additionally, we urge FDA to align its recommendations with the upcoming version of the ISO 80601-2-61 (that would replace ISO 80601-2-61:2017) for the premarket performance evaluation of pulse oximeter devices, which was developed with input from international experts, including FDA.”

Similarly, MDMA took issue with the proposed guidance for not aligning with international regulatory standards to update pulse oximetry testing requirements.

“The draft guidance sets a concerning precedent as both the FDA and industry have been participating in good faith using data-driven science from a broad stakeholder group to update ISO 80601-2-61 through the international consensus standard process,” said MDMA.

“Many of the recommendations provided in the draft guidance are not supported with scientific or statistical rationale,” the group added. “As such we recommend the current guidance be withdrawn so that the FDA can partner with industry and international stakeholders to standardize new requirements for performance testing of pulse oximeters and fully adopt the text of the future updated version of ISO 80601-2-61.”

Device maker Medtronic also raised concerns about FDA's deviation from the ISO 80601-2-61 standards. The company said that while it appreciates that the agency has referenced the standard in its guidance, it should wait until the standard is updated to ensure there's less inconsistency.

"With the extensive input already incorporated into the updated version of this standard, Medtronic believes that the relevant requirements applicable to pulse oximeters should be aligned as closely as possible with ISO 80601-2-61, once finalized," said the company. "Medtronic is concerned that deviation from this ISO standard will add inconsistency without providing any added improvements to device safety and performance."

MDMA noted that one of the major differences between FDA’s requirements and those developed for the ISO standard is the number of participants sponsors should recruit in controlled desaturation studies. ISO recommends 24 participants, but in the draft guidance, FDA significantly increased its recommendation from 10 participants to at least 150. The group listed several reasons it is concerned with such a large requirement.

“First, 150 participants are an arbitrary distinction based on the dataset of a borderline performing device and a detailed statistical justification for this sample size in this guidance document is lacking,” said MDMA. “Additionally, 150 participants may exceed the statistical needs for calculating bias and [ Accuracy Root Mean Square (Arms)].”

“Finally, commercial testing laboratories qualified to conduct this testing may be unable to support such large studies for the entire U.S. market, which could result in product shortages caused by the FDA’s recommendations without adequate time to transition,” the group added. “This product shortage could be exasperated in especially vulnerable but smaller patient populations such as neonates.”

AdvaMed also said the recommendation to include 150 or more participants in studies was arbitrary and burdensome. The group said requiring 150 participants is rigid and assumes a one-size-fits-all approach that may not be feasible for all products. It added that requiring excessive sample sizes creates unnecessary testing burdens and may exceed the statistical requirements for calculating bias and Arms.

“Commercial testing laboratories have indicated they lack the capacity to support large-scale studies across the U.S. market, raising significant concerns that FDA’s recommendation is not consistent with the least burdensome provisions,” said AdvaMed. “This limitation could lead to product shortages, particularly affecting vulnerable populations such as neonates.”

“We urge FDA to reconsider its sample size recommendation to ensure regulatory recommendations remain both scientifically justified and practically feasible,” the group added.

AdvaMed recommended that FDA have different clinical performance expectations for devices based on their intended use and setting. The group argues that the guidance applies identical performance testing expectations for all pulse oximeters regardless of whether they are used in hospitals or at home as over-the-counter (OTC) products.

AdvaMed said that applying the same performance testing requirements without consideration for their use or setting creates a significant disincentive for OTC pulse oximeter manufacturers to seek FDA marketing authorization. Such manufacturers may choose to market their devices only as wellness products, which lack clear labeling to identify them as intended only for fitness or aviation purposes.

"Currently, consumers are at risk as unregulated pulse oximeters available through various online and retail platforms vary widely in quality, accuracy, labeling, and performance," said AdvaMed. "This ambiguity in labeling could further exacerbate disparate performance when, for example, lay purchasers, procurement teams for medical offices, or any user mistakenly uses pulse oximeters intended for general wellness for a medical purpose."

"Therefore, we recommend at a minimum that FDA ensure clear labeling on pulse oximeters intended for non-medical purposes, such as those intended for general wellness and aviation," the group added.

MDMA also expressed concern that general wellness oximeters are not clearly labeled for fitness or aviation purposes. The group said consumers are currently at risk because unregulated pulse oximeters are readily available and can vary greatly in performance. They said labeling ambiguity could lead consumers to use such products in ways they're not intended for.

"Therefore, we recommend that the FDA ensure clear labeling on pulse oximeters intended for non-medical purposes such as those intended for general wellness and aviation," said MDMA. "Additionally, MDMA recommends that FDA make a public notification to alert users of the lack of FDA clearance and review of performance data for general wellness oximeters as well as the associated risks if these devices are used for a medical purpose."

The American Medical Association (AMA) also commented on the proposed guidance and asked FDA to make several improvements, including establishing accuracy standards and improving transparency in product labeling. The group argued that a lack of explicit benchmarks could cause devices to continue overestimating oxygen saturation in certain patient populations, leading to poor clinical decisions.

AMA said labeling transparency is essential to ensure patients and their physicians are informed about the limitations of the pulse oximeter depending on the patient’s skin tone. While the draft guidance recommends that the product label is clear about whether the product has been tested across diverse skin tones, it does not require disclosure of instances where the product does not perform as well.

"The AMA recognizes the draft guidance’s encouragement of transparency in reporting; however, it does not fully ensure clear disclosure of known performance limitations," said AMA. "If a pulse oximeter has been demonstrated to produce inaccurate readings in specific populations, that information should be explicitly stated in its labeling."

"Patients and providers must be fully informed of potential limitations to ensure accurate interpretation of readings and appropriate clinical decision-making," the group added. "To ensure full disclosure of device limitations, the FDA should also recommend warning labels on pulse oximeters that have been shown to reproduce bias in results across skin tones, explicitly noting the risk of inaccurate readings."

MDMA said it is also concerned about FDA’s grouping of Monk Skin Tone (MST) categories in the draft guidance deviates from the ISO 80601-2-61 standard. The group argues that the agency’s use of Monk scales to group participants and determine their Individual Typology Angle (ITA) to determine their skin pigmentation can make it challenging to recruit study participants and create an undue burden for sponsors collecting the data.

“This divergence from what will be an international consensus standard will result in duplicative labeling, regulatory divergence, and confusion across the world,” said MDMA. “We are also concerned that average clinicians, who already struggle to understand Arms, will not understand the difference between these two groupings. We recommend that the FDA adopt the same MST groups as the future updated version of ISO 80601-2-61.”

While recognizing that clinical practice is beyond the scope of FDA's regulatory mandate, AMA asked FDA to take steps to ensure physicians are well-informed about the pulse oximeters they may use in their practice. The group said educational materials specific to pulse oximeters could help avoid misdiagnoses and potentially bad clinical decisions.

"Given the FDA’s role in advancing medical device safety through Letters to Health Care Providers, which communicate essential information about the safe use of medical devices in clinical settings, the AMA encourages the agency to incorporate guidance on pulse oximeter accuracy limitations into these communications," said AMA. "Strengthening provider awareness through this existing channel would help mitigate the impact of measurement variability and improve patient outcomes."

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Stakeholders: FDA should align pulse oximeter guidance with updated ISO standard

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