Code of Federal Regulations (CFR) Title 21 Part 820: Quality System Regulation (QSR) 21 is strangely silent on the topic of method validation. It never actually mentions the words “method” and “validation” side by side. Even so, the expectation, as evidenced by warning letters dating back to at least 2005, is that method validation is an applicable medical device validation activity.
Due to the actual regulation being silent on the topic, there are a variety of industry and regulating agency interpretations on how method validation activities can and should be applied for medical devices. The traditional definition for test method validation has been applied to chemical and microbial acceptance testing methods. These types of methods are generally less utilized in the medical device industry. However, ignoring the topic because it is not specifically discussed may result in product recalls and negative financial impacts.
The very first sentence of the 21 CFR 820 scope states:
“Current good manufacturing practice (cGMP) requirements are set forth in this quality system regulation. The requirements in this part govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use.”
Title 21 Code of Federal Regulations Part 211.165 (e)
(e) The accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented. Such validation and documentation may be accomplished in accordance with 211.194(a)(2).
In spite of the omission of method validation as a named requirement, the agency has in fact issued 483s and even warning letters for insufficient or absent “Method Validation” activities.
Unfortunately, there is no further guidance on the topic other than the fact that the CDRH does use and recognize the Consensus Standards that in some cases specifically require method validation. These applicable consensus standards are covered in later sections.
At a minimum, System Suitability Testing using a Gauge R & R study should be executed to prove the method/gauge is suitable.And ensure that the actual method validation protocol must include:
Definition of the application, purpose, and scope of the method
Analytes, concentrations, sample/parameter matrices
List of parameters/conditions/materials to be tested
Draft analytical method
IQ/OQ/PQ of instrument references
Instrument calibration references.
Hope this helps!