- Specificity of the tests not established
- Procedures describing the calibration of instruments are deficiently written or followed
- Records maintained of any modification of an established method employed in testing do not include the reason for the modification, the data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.Here are the observations in detail. These can be our interpretation of the observations in general terms or replicated from the Form 483 if they are too technical in nature:
Specificity of the tests not established
As part of the test method validation step – the stress (forced degradation) studies done for a particular product failed. Additionally the chromatographic purity test profile [Chromatographic Purity means presence of unknown impurity, calculated by % area] was found different than that obtained during the method validation.
The data supporting validation activities performed to demonstrate the suitability and adequacy of the analytical method used for the release and stability testing of a particular API was found to be inadequate and incomplete.
Validation Documents showed that the validation of the methods does not contain complete forced degradation studies.
Procedures describing the calibration of instruments are deficiently written or followed
Calibration of the Gas Chromatographic [common type of chromatography used in analytical chemistry for separating and analysing compounds that can be vaporized without decomposition] was incomplete. The following were not covered in the calibration report – oven temperature, noise and drift, signal to noise and detector accuracy tests.
Records maintained of any modification of an established method employed in testing do not include the reason for the modification, the data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.
Test method for the ultraviolet Absorption as part of USP monograph identification test was not followed. Calculations were performed with the absorbance readings instead of absorptivity [more here on the difference]. These modifications to the USP test method and calculation formulas were not validated.
While most of the observations are too technical in nature, we believe the second and third observations to be less critical since it is a procedural process that can be resolved with the help of the manufacturer of those instruments.
We think the first observation on test methods is something that the company may have to fix immediately since the FDA team needs to be satisfied by a detailed answer/ remediation or through a re-inspection alone.