How is pulse oximeter clinical validation done for FDA 510k clearance and ISO CE marking?

For FDA or ISO clearance, pulse oximeters must undergo testing in healthy human study subjects.

ISO 80601-2-61 defines the test requirements, and the FDA has published guidance that refers to this standard. The standard requires the devices to be tested with a minimum of 200 data points (paired observations: pulse oximeter, co-oximeter) evenly distributed over an SaO2 range of 70% to 100%. The standard requires that devices be tested on “10 or more healthy subjects that vary in age and gender” and that the study has subjects with “a range of skin pigmentations, including at least 2 darkly pigmented subjects or 15% of the subject pool, whichever is larger.”

Briefly, study subjects are semi-supine (30° head up) with a nose clip (to prevent breathing through the nose), breathing controlled mixtures of air-nitrogen-carbon dioxide via a mouthpiece from a partial rebreathing circuit with a voluntarily increased minute ventilation (sometimes coached with a metronome) and 10 to 20 L/min total fresh gas flow into the circuit. A 22-g radial artery catheter is placed to sample arterial blood for the measurement of SaO2. 

The gas mixture (e.g. nitrogen) of the circuit is manually adjusted to achieve a series of 10 to 12 stable SaO2 plateaus between 70% and 100% (approximately 70%, 73%, 76%, 80%, 83%, 86%, 89%, 92%, 95%, 98%, and 100%). Carbon dioxide is manually increased into the circuit to prevent hypocapnia. At each plateau (after 30-60 seconds of stability) an arterial sample is drawn and immediately “functional” arterial Sao2 (HbO2/[Hb+HbO2]) is determined by multi-wavelength oximetry (e.g. an ABL-90, OSM3 or similar device). After an additional 30 seconds of stability another sample is drawn. These SaO2 values are recorded and used to compare with recorded simultaneous SpO2 values from the device being tested.  During the tests, subjects’ extremities may be placed under a warmer to promote good perfusion. 

References: FDA Guidelines 

Keywords: FDA, guideline, clinical, accuracy, 510k, approval, ISO