IDENTIFYING AND ASSESSING OOS TEST RESULTS:- FDA regulations require that an investigation be conducted whenever an OOS test result is obtained. The purpose of the investigation is to determine the cause of the OOS. Even if a batch is rejected based on an OOS result, the investigation is necessary to determine if the result is associated with other batches of the same drug product or other products. Batch rejection does not negate the need to perform the investigation. The regulations require that a written record of the investigation be made including the conclusions of the investigation and follow-up (211.192). To be meaningful, the investigation should be thorough, timely, unbiased, well-documented, and scientifically defensible. The first phase of such an investigation should include an initial assessment of the accuracy of the laboratory’s data, before test solutions are discarded, whenever possible. This way, hypotheses regarding laboratory error or instrument malfunctions may be tested using the same test solutions. If this initial assessment indicates that no errors were made in the analytical process used to arrive at the data, a complete failure investigation should follow.


  • Responsibility of analyst:- For achieving accurate laboratory testing results first responsibility is lies with the analyst. He is aware of potential problems which occur during the test process and he will watch the problems which could create in accurate results. According to 211.160(b) (4) the instruments which meet the specifications that are used and these are properly calibrated. Those analytical methods have system suitability requirements the system which are not meeting the specification that should not be used. The causes of malfunction should be identified and it should be corrected before decision is made.


  • Responsibilities of superior:- OOS result has been identified higher judgment should be timely and objective. The results should indicate problems in the manufacturing process. Immediate assessment should include the test units and re-examination of test results and glass wares used in the preparations. For laboratory error hypothesis it provides more Part of superior assessment the following should be taken:-


  1. The test method has to be discussing with the analyst and conformation analyst knowledge and performance of procedure.
  2. In the analysis examine the raw-material which is obtained including spectra, chromatograms and identify suspect information or anomalous.
  3. Calculations are verified which used to convert raw data values into final values which are appropriate, correct and scientifically sound and also determine if any un validated changes have been made in automated calculation methods.
  4. Performances of instruments are conformed.
  5. Determine the solvent reagents, other solutions and appropriate reference standards were check whether it met the quality control specifications.
  6. Performance of test method evaluated to ensure that the performing according to standards and based on historical data and method validation data.
  7. It is documented and records should be preserved of this laboratory assessment.


If the returned samples are examined promptly cause of OOS results should be facilitated. What might happened regarding to hypothesis like instrument malfunction and dissolution error should be tested. Part of laboratory investigation examination of retained solutions should be performed.


 General Investigational Principles:- A failure investigation should consist of a timely, thorough, and well-documented review. The written record should reflect that the following general steps have been taken:-

  1. The reason for the investigation has been clearly identified.
  2. The manufacturing process sequences that may have caused the problem should be summarized.
  3. Results of the documentation review should be provided with the assignment of actual or probable cause.
  4. A review should be made to determine if the problem has occurred previously.
  5. Corrective actions taken should be described.

The general review should include a list of other batches and products possibly affected and any required corrective actions taken including any comments and signatures of appropriate production and quality control personnel regarding any material that may have been reprocessed after additional testing. 

Laboratory Phase of an Investigation:- A number of practices are used during the laboratory phase of an investigation. These include:-

(1) retesting a portion of the original sample,

(2) testing a specimen from the collection of a new sample from the batch,

(3) resampling testing data, and

(4) using outlier testing.

  1. Retesting:- Retesting of a portion of the original sample involves part of the investigation. From the same homogeneous material the sample should be taken for the retesting 15. In case of a liquid it may be from the original unit liquid product or composite of the liquid product; in case of a solid, it may be an additional weighing from the sample composite prepared for the original test. Situations where retesting is required include investigating testing instrument malfunctions or to identify a possible sample handling problem, ex: a suspected dilution error.
  2. Re-sampling:- Analyzing a specimen from any additional units collected as part of the original sampling procedure or from a new sample collected from the batch is involved in the re-sampling. There should be sufficiently large original sample from a batch to accommodate additional testing in the event an OOS result is obtained. Examination of additional specimens should be done in accordance with standard operating procedures and sampling strategies.
  3. Averaging:- Together appropriate and inappropriate uses of averaging test data are included during OOS investigation and original testing are there in averaging:-
  • Appropriate uses:
  1. Averaging data usage depends upon the sample and its purpose. More accurate results can be obtained using averages if sample is homogeneous.
  2. USP recommends the use of averages for microbiological assays as they have innate variability in the biological test system.
  • Inappropriate:
  1. Confidence on averaging has the disadvantage of smacking variability among individual test results. For this reason, all single test results should normally be reported as separate values. 

Outlier Tests:

  • CGMP guidelines prefer that statistically effective quality control criteria should include suitable acceptance and/ or rejection levels.
  • Outlier outcomes in a deviation from set test methods.
  • Reason for an outlier is due to the fault in the testing procedure and not due to the characteristic variability in the sample being tested.
  • This testing is numerical to recognize those that are extreme from an array. Of outlier test should be written into SOPs for data explanation and be well documented. Specific outlier test to be applied with relevant parameters stated in advance are to be included in SOPs. These should also state the minimum number of outcomes required to obtain a statistically important assessment from the stated outlier test.

CONCLUSION:- In this test, the batch quality should be determined, the results should be assessed, and a release conclusion should be made by the QCU. In this case SOPs should be followed in incoming at this point. There is no limit to advance testing to determine the cause of the failure, when a batch has been rejected. 

Interpretation of Investigation Results:

  • Interpreting the consequences of the investigation will be done by QCU. Conclusion (rejection or failure of batch) should not be taken based on the early OOS results.
  • If the supposed result is invalidated then the outcome should not be used to assess the quality of the batch or lot. Invalidation of the distinct test result rest on only up on the observation and documentation of a test result.
  • OOS result gives a sign that the batch does not meet required qualifications and this outcome in batch’s rejection, in accordance with $211.65 (f), and appropriate disposition. For insufficient investigations OOS result should be given at most important in the batch or lot disposition conclusion.
  • In case when OOS was modified, the investigation will changes from an OOS study into a batch failure investigation, which must be extended to other batches associated with the exact failure.
  • If OOS was not modified (inconclusive), the QCU might still finally decide to release the batch.

Field alert Reports:

  • Products which are accepted and shortened new drug submissions require submitting a field alert report within 3 employed days.
  • A Field alert report comprises facts concerning any failure of a distributed batch to meet any essential conditions.
  • If the OOS result on the dispersed was found to be unacceptable within 3 days, an initial FAR should be submitted. When the OOS examination is completed a track-up Field alert reports (FAR) should be submitted.


Reference links


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