What is the definition of terminologies used in oOS investigation?
For investigation of Out Of Specification (OOS) results multiple terminologies are used to get a proper root cause, here some terminologies are defined.
1. OOS Results: A result that is not confirmed and reported as a failure by the analyst-1 through first analysis, which is considered to be doubtful and needs to be investigated. This also takes account of discrete test results ( specifically when the testing is performed in replicates) irrespective of whether the average is within the pre-determined/established specifications or acceptance criteria or not.
2. Acceptance Criteria: The Numerical limits range for acceptance of test results.
3. Investigation: A documented analysis was conducted to discover facts and clues in order to determine the root cause.
4. Investigator: A supervisor or any other designated personnel nominated by HOD, with subject knowledge by virtue of their qualification and experience whosoever performs failure investigations individually or in coordination with/support from personnel or investigation team.
5. Laboratory Error: An error associated with the performance of a test procedure or due to laboratory equipment malfunction or failure.
6. Obvious Error: Errors that are clearly evident such as wrong glassware used, Wrong weight is taken, incorrect instrument setting, Inappropriate number of dosage units, power outage, calculation error, equipment failure, spillage of sample solution, incomplete transfer of sample composite which is identified by analyst and/or investigator shall be referred as “obvious error”.
7. Invalidated Test: A test is considered invalid when the investigation has determined the laboratory error, which has resulted for OOS results.
8. Analyst-1: Analyst who has performed the analysis of initially reported results.
9. Analyst-2: A 2nd analyst involved in performing additional testing/retest as per requirement in the OOS investigation. Who is as least as experienced and qualified in the method as the analyst 1.
10. Probable Cause: Identifiable factors, which are most likely to have resulted for batch failure, but has not been scientifically proven and which needs to be further established through hypothesis activities.
11. Assignable Cause: A scientifically justified explanation of the reason for an OOS test result identified and documented during the investigation.
12. Experimental study: Studies conducted with an objective to identify any probable causes that could result in failures.
Such studies shall be conducted only after prior approval from QA. The discrete outcome of experimental activity shall not be used for taking decisions on batch disposition or reporting the final results.
13. Hypothesis Study: Activities conducted to prove or disprove the probable causes from the assumptions made i.e. what might have happened ( such as during sample filtration/centrifugation/Holding/processing/packaging, etc) that can be studied.
Such activity shall be conducted only after prior authorization from QA, by recreating the analysis condition, or by simulation/repetition of a process, which is identified as probable cause.
14. Laboratory Investigation (Phase-I): Investigation carried out to assess the accuracy of laboratory testing and recording in order to identify whether there was any laboratory error have resulted in OOS result for the batch in question. This investigation includes a review of sample handling, storage of sample prior to analysis, examination of standard and sample preparation, and testing in the laboratory against the documented procedures and also the practices associated with testing which may not be covered in the test procedure.
15. Full-scale investigation (Phase-II): Detailed investigation into manufacturing of the product and process to identify the root cause for batch failure. This included a review of various records and process simulation & /or experimentation where required and may also include retesting of the same sample in statistically significant replicates if necessitated.
16. Non-routine sample: Sample which is other than routine samples; such as vendor evaluation sample. Innovator or other market samples, sample employed for method transfer, Outputs of lab-scale batches wherein an evaluation is done by supervisor only to ascertain any laboratory error.
17. Correction: Repair, Reprocess, rework or adjustment relating to the disposition of an existing discrepancy.
18. Corrective Action: Corrective actions aim at eradicating the causes of existing problems and nonconformities, defects, or other undesirable events so they cannot recur again. Corrective action is also known as Remedial action.
19. Preventive Action: A preventive action strategy eliminates unacceptable future events and nonconformities by eliminating the causes of unwanted events and nonconformities.
20. Root Cause: Root cause describes a chain of events that led to a direct cause – so a series of contributing factors that enabled the problem to occur. OR The underlying cause, identified based on scientific evidence, which is responsible for the lab error/batch failure.
21. Root Cause Analysis: This process involves identifying the first step that leads to the sequence, which in turn leads to the problem, and determining how to solve this problem. or
A root cause is any factor that caused a nonconformance and should be eliminated permanently by process improvement.
22. Impact Assessment: An assessment carried out to evaluate the impact on an incident on current batch/product along with other batches/products, processes, procedures, sites, products in market, patient safety, regulatory filing, vendor qualification etc.
23. Effectiveness check: An action taken to verify that the expected results are achieved i.e. that the corrective and/or preventive actions prevent the occurrence or recurrence of the incident.
24. Batch Disposition: Action to be taken on the batch in question based on the conclusion of the investigation. Action may include reject/reprocess/rework/release/recall/ (In case, if OOS is confirmed on stability samples of commercially distributed batches).
25. Invalid OOS: An OOS considered invalid, when the investigation has determine the laboratory error or any error other than the manufacturing resulted for the observed failure results
26. Valid OOS: An OOS considered valid, when the investigation outcome confirms the observed failure result.
These are some definition of terminologies used in OOS investigation in the pharmaceutical industry.
Also Read:
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- CAPA process in a pharmaceutical management system
- Practices to avoid data integrity and alcoa plus
- Laboratory investigation of abberent results part 3
- Difference between assay, potency and purity
- GAMP 5 software categories
- HPLC interview question and answer
- Preparation and standardization of 1N NaOH
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