Laboratory Investigation Of Aberrant Results Part-3

Laboratory Investigation Of Aberrant Results part-3

In the last 2 parts, we covered 5 points of laboratory investigation of aberrant results. Here we will cover the remaining 4 points such,

  • Laboratory chemicals and reagents
  • Laboratory equipments
  • Additional laboratory testing
  • Miscellaneous points

Laboratory Investigation:

Laboratory chemicals and reagents:

Quality & Integrity:

Visually examine the reagents and chemicals used for any evidence of degradation or deterioration.

For Example; Discoloration, Precipitation, Uncharacteristic odor, etc.

Expiration dates:

Check the preparation and expiration dates of the chemicals and reagents. Verify that the solutions and reagents are standardized before use.

Storage Conditions:

Verify the chemicals, reagents & solutions are stored as per specified conditions. Also, crosscheck for the absence of contamination & cross-contamination from prolonged storage & usage.

Laboratoty Equipments:

Potential equipment problem:

Check the equipment logbook & maintenance history, to determine whether the equipment has gone under major breakdown previously, or required frequent repairs or adjustment.

Equipment Precision, Accuracy, and integrity:

Ensure that the equipment used was in the calibrated status and complied with all the acceptance criteria.

Check historical data for its correct & consistent results for the previous analysis and calibration.

Verify that there was no malfunction or failure before the analysis.

Equipment Contamination:

Verify that the equipment was checked for its cleanliness or cleaned prior to use. Check that there were no chances of equipment contamination due to foreign matter or previously analyzed followed.

Chromatographic System:

Cross-check the instrument method used was as per the analytical method and all the chromatographic conditions are followed.

The correct column was used as per the standard test procedure & conditioned for sufficient time prior to use.

Check the column usage card for the previous usage of the column & the number of injections performed till date on the same column. Also, crosscheck the efficiency & reproducibility of the column used.

Check for the compliance of the system suitability parameters, peak shape & compliance for the bracketing standard also.

Review the processing method & verify it for proper chromatographic integration of interested peak/peaks.

Also, cross-check the buffers used for analysis has been degassed & filtered properly. Determine how long the buffers/mobile phase has been used. Any potential of the degradation of the mobile phase/any haziness in the mobile phase.

Review for any abnormal observation in the chromatographic run throughout the analysis.

Additional Laboratory Testing:

A full-scale OOS investigation may include additional laboratory testing. A number of practices are used during the laboratory phase of integration.

These include,

1) Phase-1 OOS Investigation:

During phase-1 investigation reassessment of the original laboratory sample solutions and/or repeat test shall be performed. As approved by management. This phase included re-analysis, re-dilution, re-injection/re-scan, standard study and repeat test.

2) Phase-2 OOS Investigation:

In case when no obvious laboratory error exists and no extraction, dilution, injection or standard preparation error are evident as determined in phase-1.

Thus, the investigator should initiate a retest with the goal of determining the assignable cause of the aberrant results. All actions of this phase must be justified based on sound scientific judgment, documented, and approved before proceeding for analysis.

3) Phase-3 OOS Investigation:

If the investigation, thus far, indicates that the aberrant results cannot be assigned to laboratory error, the resampling and retesting of the batch may be initiated. Management personnel, at a minimum of Manager Level, or designee, from Quality, must approve re-sampling by his or her signature.

It should be noted that repetitive phase 3 test plans are not permitted without a scientifically justified and unique assignable cause theory.

Miscellaneous Points:

Verify the following points,

  • All the computer systems used for the analysis, data transfer & calculation are validated.
  • The history of the sample and test method for any similar problems or variations in privious test results.
  • Whether there were any unusual or atypical occurances during the analysis.
  • Any minor error/deviation/variation occured during analysis, which has not been observed/identified by the analyst.Determine any impact of such minoe error/deviation on the results.
  • Whether there were any adverse environmental conditions during the testing of the sample (Such as temperature & Humidity fluctuations, voltage variations etc.)

Final Conclusion:

  • Purpose of investigation is to identified to the possible root cause.
  • The investigation shall be carried out for the affected batches.
  • In case of probable root cause was not identified as analytical error, then the investigation shall be extended for manufacturing.
  • The investigation shall include the necessary corrective action and preventive action (CAPA). The CAPA shall be verified for its implementation & effectiveness to avoid the recurrence of the issue.
  • An initial OOS result does not necessarily mean the subject batch fails and must be rejected. The OOS results should be investigated, and the findings of the investigation, including the retest results, should be interpreted to evaluate the batch and reach a decision regerding release or rejection.

Also Read:

  1. Laboratory Investigation Of Aberrant Results Part-1
  2. Laboratory Investigation Of Aberrant Results Part-2
Laboratory Investigation Of Aberrant Results
Laboratory Investigation

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