1/2 December 2021
The U.S. Food and Drug Administration (FDA) inspected the drug manufacturing facility, BBC Group Limited, located in China, from March 22 to March 26, 2021. During the inspection, significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals were found. One of the points raised concerns the validation of analytical test methods.
ICH Q2 (R1) "Validation of analytical procedures: text and methodology" presents a discussion of the characteristics that should be considered during the validation of analytical procedures. General principles and approaches that FDA considers appropriate elements of method validation can be found in the FDA's guidance document "Analytical Procedures and Methods Validation for Drugs and Biologics".
Validation can be defined as follows:
In the Warning Letter dated August 4, 2021, the FDA criticises, among other aspects, that analytical test methods were not adequately validated, including those for the active ingredient ethanol, which the company uses to manufacture alcohol-based hand sanitizers. In the warning letter, it is stated that "specifically, no system suitability requirements were present and reference standards were not identified. Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy, sensitivity, specificity, and reproducibility and are suitable for their intended purpose."
In the response to Form FDA 483, which preceded the Warning Letter, the company indicated that test methods were updated, method validation protocols established, and test method evaluation completed. However, the FDA considered the response as inadequate. The FDA missed the following relevant aspects:
For further information, including the other findings made by the FDA, please read the full Warning Letter to BBC Group Limited published on the FDA website.