July 29, 2021

FDA’s 21 CFR §820.72 Metrology Requirements vs. Test Method / Process Validation

My experience has been that FDA views a test method as a process that produces an output.  And if such output can’t be fully verified, then it must be validated.  Since FDA’s 21 CFR §820.72 is not generally related to “validation” (a very specialized, very robust, very deliberate term defined by §820.3), I’ve seen FDA handle process validation (be it for a production process yielding a tangible physical output or for a test method producing a data output) via §820.75.  For example, in a February 19, 2002 Warning Letter, FDA states, “…[we]…collected information that revealed serious regulatory problems…as follows:…Failure to validate with a high degree of assurance a process that cannot be fully verified by subsequent inspection and test as required by 21 CFR 820.75(a). For example:…The testing procedure used for…has not been validated…”

I would be very hesitant to try and integrate the principles of “validation” into my instrument metrology program.  That’s not something I’ve seen before in the many metrology programs I’ve encountered.  FDA and its explanations of §820.72 are generally aimed at assuring metrological adequacy of instruments rather than the adequacy of test/measurement processes.

Another way to put my experience is that §820.72 is related to the principles embodied by ISO 10012 / EN ISO 10012 clause 7.1 (metrological confirmation, i.e., “calibration”), whereas “validation” is instead related to the principles embodied by that standard’s clause 7.2 (measurement process development and validation).  Those sections provide a nice distinction between instrument metrology vs. measurement process (e.g., test method) validation.  They show that clause 7.1 (and I would say §820.72) is to ensure that metrological instruments are fit for their intended use, whereas 7.2 (and I would say §820.75) ensure that a process (e.g., a measurement process, i.e., a test method) is fit for the process’s intended use.

Because of these principles, my experience is that FDA generally associates test method validation with §820.75 rather than §820.72.  As mentioned above, I’ve seen FDA issue test method validation audit citations against §820.75 rather than §820.72.  So it seems that FDA definitely demands that we perform test method validation pursuant to §820.75 rather than §820.72.  If we applied the principles of §820.72 for test method validation, then I would get ready for a real wallop from FDA and other regulators like ISO auditors.