What are Out of Specification results (OOS)? It seems to be clear enough in the name but I thought I better check it out.
One definition is:
All test results which fall outside the specifications or acceptance criteria established in drug applications, drug master files (DMFs), and official compendia or by the manufacturer. In addition it encompasses all in- process laboratory tests that are outside of established specifications.
Tests are applied to:
- Active Pharmaceutical Ingredients (APIs)
- Excipients
- In-process materials and
- Finished products
These tests are carried out to ensure that the products conform to specifications, including stability specifications and are carried out in accordance with cGMP regulations.
If an OOS occurs it has to be investigated to identify the root cause. The investigation start with an assessment of the accuracy of the data but if this is deemed to be a true result and no errors were identified in the process carried out , this then will trigger a full OOS investigation which should be:
- Thorough
- Timely
- Unbiased with no preconceived assumptions
- Well- documented
- Scientifically sound
- The knowledge and training of the analyst may also be assessed
- The calibration of equipment will be considered
- Method, reagents and solutions will be checked and verified.
The investigation will involve the analyst, their supervisor, OOS should be relatively rare, so if there are any abnormal trends this should be investigated further to ensure laboratory or human error in the laboratory are not at fault.
If it the investigation requires a review of the production, then all the relevant sites must be included in the investigation. A written record of the review will be collated and should include
- The reason for the investigation
- The aspects of the manufacturing process that may have caused the problem
- The results of the document review
- The results of the review made to determine if the problem has occurred previously
- The corrective actions taken.
An OOS may occur for a multitude of reasons however a flaw in the product or process design must be considered.
Retesting may be required by another analyst, another or the same batch of product. Testing until you achieve compliance is not good practice. Averaging may be appropriate however it is not always. All separate values should be recorded.
All investigations must have a conclusion and the QP or QCU will have the final say and should always err on the side of caution.