The CGMP regulations require the use of validated methods when performing routine testing of raw material, in
process material, and finished product (21 CFR 211.160, 211.165(e), and 211.194) for manufacturing finished
drug products. Method validation studies establish proof that a method is suitable for its intended purpose. The
purpose is generally to measure a particular material’s conformance to an established specification (see FDA
Guidance for Industry, ICH Q2 (R1)).
FDA recognizes, however, that test methods developed based on scientifically sound principles (e.g., sufficient
accuracy and precision) but which are not fully validated may be suitable for use in certain instances during an
investigation of a potential quality problem or defect. For example, investigation of an atypical impurity or
possible contaminant of a drug product or any of its components (e.g., OSCS in heparin) may indicate the need
for additional methods beyond routine quality control tests. Such testing may be critical to promptly and
adequately evaluate the problem and protect public health. Full evaluation of a method’s robustness and
reproducibility may not initially be feasible or appropriate when conducting tests in certain investigations.
When a company, for whatever reason, tests drug components or products using an unvalidated method, it is
important to recognize the possibility of greater uncertainty in the test results derived from these unvalidated
test methods, as compared to validated test methods. Nevertheless, the resulting data may yield important
information indicating the need for prompt corrective action. Accordingly, we expect all such test results on drug
components or products to be reviewed to assess the need for follow-up action
