OOS RECORDING PROCEDURE
- REPORTING TO THE LABORATORY SUPERVISOR
- RECORDING AND NUMBERING OF OOS
- INVESTIGATION BY ANALYST
- LABORATORY TESTING
- APPROVAL BY LAB. SUPERVISOR
- TESTING BY ANALYST
- PROCEDURE OF OOS
- A written record of the review should include the following information
- A clear statement of the reason for the investigation.
- A summary of the aspects of the manufacturing process that may have caused the problem.
- The results of a documentation review, with the assignment of actual or probable cause.
- The results of a review were made to determine if the problem has occurred previously.
- A description of corrective actions taken. Manufacturing/ Production Process Review Investigation
If an error is found, the investigation is terminated & product rejected
- However, a failure investigation that extends to other batches or products that may have been associated with the specific failure must be completed
- If reprocessed after additional testing, the investigation should include comments and the signatures of appropriate production and quality control personnel
- Appropriate CAPA should be taken Manufacturing/ Production Process Review Investigation Should be conducted by QA.
- Should involve all another relevant departments i.e. production, development, engineering, if needed If the contract manufacturer then all sites (contract manufacturing site).
- Timely, thorough, and well-documented Manufacturing/ Production Process Review Investigation,Additional Laboratory Testing Retesting Resampling Investigation
Additional Laboratory Testing :
- Decisions should be taken based on the objective of the testing & should have sound scientific judgment
- Should have a predefined retesting plan
- Should be done by an analyst other than the original analyst
- 2nd analyst should be qualified at least like the original analyst
- should be from the same sample portion which has generated OOS results Investigation Retesting
Additional Laboratory Testing:
- Should be done to identify instrument malfunction, sample handling error e.g. dilution error
- Testing for compliance is prohibited
- The maximum number of retests should be defined in SOP and should not be adjusted depending on the obtained result
- The firm’s predetermined retesting procedures should contain a point at which the additional testing ends and the batch is evaluated
- If the results are unsatisfactory at this point, the batch is suspect and must be rejected or held pending further investigation Investigation Retesting
- Any deviation from SOP should be rare and any deviations from written specifications, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified.
- In such cases, before starting additional retesting, a protocol should be prepared (subject to approval by the QA) that describes the additional testing to be performed and specifies the scientific and/or technical handling of the data. Investigation Retesting
- In the case of a clearly identified laboratory error, the retest results would substitute for the original test result. All original data should be retained, however, and an explanation recorded This record should be initialed and dated by the involved persons and include a discussion of the error and supervisory comments.
- If no laboratory or calculation errors are identified in the first test, there is no scientific basis for invalidating initial OOS results in favor of passing retest results. All test results, both passing and suspect, should be reported and considered in batch release decisions. (In other words, all data are reported in, for example, quality control reports, batch records, and Certificates of Analysis) Investigation Retesting
- Should rarely occur
- If an insufficient quantity of the original sample remains to perform all further testing then the procedure for obtaining a resample must be discussed and agreed upon by QA/Contract Giver/QA equivalent. The process of obtaining the resample should be recorded within the laboratory investigation.
- Re-sampling should be performed by the same qualified methods that were used for the initial sample. However, if the investigation determines that the initial sampling method was in error, a new accurate sampling method shall be developed, qualified, and documented.
- It involves collecting a new sample from the batch.
- This will occur when the original sample was not truly representative of the batch or there was a documented/traceable lab error in its preparation.
- Evidence indicates that the sample is compromised or invalid.
- Sound scientific justification must be employed if re-sampling is to occur. Investigation
If the batch is rejected there still needs to be an investigation.
- To determine:
- if other batches or products are affected.
- Identification and implementation of corrective and preventative action.
Conduct Phase III Investigation Investigation
PREPARATION OF TEST REPORT
- EVALUATION OF SUSPECT RESULTS
- INVESTIGATION BY THE TECHNICAL MANAGEMENT TEAM
- CONCLUSION AND REPORT OF DATA
- EVALUATION BY QUALITY MANAGER
Investigations of “Out of Specification (OOS) / Out of Trend (OOT)/ Atypical results” have to be done in cases of
- Batch release testing and testing of starting materials.
- In-Process Control testing: if data is used for batch calculations/decisions and if in a dossier and on Certificates of Analysis.
- Stability studies on marketed batches of finished products and or active pharmaceutical ingredients, ongoing/follow-up stability (no stress tests)
- Previously released batch used as a reference sample in an OOS investigation showing OOS or suspect results.
- Batches for clinical trials.
- All solutions and reagents should be retained until all data has been second person verified as being within the defined acceptance criteria.
- Pharmacopeia has specific criteria for additional analyses of specific tests (i.e. dissolution level specification for S1, S2 & S3 testing; Uniformity of dosage units specification for testing of 20 additional units; Sterility Testing).
- If the sample test criteria are usually the first level of testing and a sample has to be tested to the next level this should be investigated as it is not following the normal trend.
- The OOS process is not applicable for In-process testing while trying to achieve a manufacturing process end-point i.e. adjustment of the manufacturing process. (e.g. pH, viscosity), and for studies conducted at variable parameters to check the impact of drift (e.g. process validation at variable parameters). Investigation
Re-testing: The analysis of the original sample at the time of phase- I laboratory investigation.
Re-sampling: The original batch is sampled by QA a second time after QA head authorization for re-analysis.
Re-analysis: The analysis of re-sampled material for the verification of results, if the manufacturing investigation does not have a root cause.