It is hard to believe, but every now and then people make mistakes. Analysts might not have had coffee in the morning or were up too late playing video games and make a mistake during laboratory testing.
In the pharmaceutical industry, whenever out of specification (OOS) results are generated, there is a rigorous methodology utilized to investigate the result and determine its validity (FDA Guidance for Investigating Out-of-Specification Results). This generally involves hypothesis testing with retesting to prove that there was actually laboratory error before the results can be invalidated. It is unacceptable practice to invalidate and repeat testing without confirming a laboratory error occurred. In the case where laboratory error cannot be conclusively determined, FDA labs are required to report all results generated.
But not all errors can be detected. If the testing results are not out of specification, then no investigation is performed. The review of the paperwork might indicate that the incorrect equipment or reagent was used, which would invalidate the testing – but even reviewers make mistakes. There is a rule of thumb in industry that 100% inspection by a second party catches 87% of errors. Finally, if the analyst inadvertently changed something that is not documented and it didn’t change the result, it may not ever be detected.
So what do we do in this environment?
- Start with documented test methods. This means we have a process that is trained on and expected to be followed by the analyst every time they run a test – no changes or shortcuts allowed.
- Implement change control for these test methods. The documents themselves are PDFs and cannot be changed without going through a rigorous review process which ensures any changes to a test method don’t impact past testing/results and does not require the method to be re-validated. For example, a typo correction or clarification of a test step do not impact the method validation and can go through the change control process relatively quickly. A change to a piece of equipment (like adding an alternative HPLC column if the old column is no longer being manufactured) would require the method to be re-validated.
- When there is an error, we work to minimize future reoccurring errors using continuous improvement methodology like Corrective Action Preventive Action. As a corrective action, we review the method to see if it should be revised to clarify the requirement and prevent future errors. As a preventive action, we look at all of the other methods that may be affected in the same way and revise them to.
This approach is the industry standard, and it drives laboratories like ours to continuously improve our methods, which means over time they become more robust.
While nobody likes to be the cause of a laboratory error, it happens. The key is how an organization responds to the error to prevent it and other similar errors from repeating in the future.