FDA guidance for handling OOS results was updated in May 2022 and is available on the FDA website. This guidance provides current thinking on the evaluation of out-of-specification results. MHRA guidance on handling OOS results was initially published in 2013 and was updated in 2018 to add handling of microbiological OOS.
There are 3 phases of an OOS/OOT/Atypical result investigation. During Phase 1 and 2, the investigation is performed to determine the root cause of OOS in the lab and manufacturing, respectively. During phase 3, a holistic assessment is performed to determine the impact of OOS results on the impacted & other batches, stability, etc., file Field alert or BPDR (If applicable), and implement appropriate CAPA.
Laboratory errors should be rare. Frequent lab errors suggest a problem in the laboratory. Lab management should implement a program to monitor trends of Invalid tests based on the root cause to enhance assay robustness, procedures, task training, implement CAPA, and prevent the reoccurrence of invalid tests. The potential or most probable root causes should be determined, where root cause cannot be determined and appropriate CAPA should be implemented for process improvements with effectiveness verifications.
Similarly, Frequent OOS suggests a flaw in the method or process or product design. If there are numerous OOS for the same test where the root cause cannot be determined, then the question arises if the specifications are adequate for the test. Is there a need to improve or redesign the process and method to ensure product quality? Also, if there are numerous OOS for the different tests where the root cause cannot be determined, then the OOS investigation procedure and training on root cause investigation needs to be enhanced.
In conclusion, a good trending program for invalid tests and confirmed OOS tests is very important to implement an effective CAPA and prevent recurring Invalid/OOS issues.