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 ly 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 these unvalidated test methods, as compared to validated test methods. Nevertheless, the resulting data may yield important information indicating the need for 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 (211.192 and 211.180(e)).
