Laboratory Investigation Of Aberrant Results Part-1

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Laboratory Investigation Of Aberrant Results in pharmaceuticals part-1:

Introduction:

During the daily analysis, we come across various types of aberrant results and incidences such as:

  • System Suitability Failure
  • Out of Trend Results (OOT)
  • Out of Specification Results (OOS)
  • Extra peak/differenr or abnormal elution patterns

During a routine investigation, along with the SOP’s some major points are mentioned here which should be covered in the investigation.

This investigation is applied to all laboratory testing and drugs. These laboratory tests are performed on Active Pharmaceutical Ingredients, excipients and other components, In-process materials, and finished drug products.

Specifically here discussed how to investigate aberrant test results, including the responsibilities of laboratory personnel, the laboratory phase of the investigation, additional testing wherever required, when to extend the investigation & the final evaluation of all test results.

An investigation should be conducted whenever aberrant test results are obtained. The purpose of the investigation is to determine the cause of the aberrant results.

Even if the batch is rejected based on OOS results, the investigation is necessary to determine if the result is associated with other batches of the same drug product or other products.

A written record of the laboratory investigation of aberrant results should be made, including the conclusion and follow-up & implementation of Corrective And Preventive Action (CAPA).

The investigation should be thorough, timely, unbiased, well-documented and scientifically sound.

Laboratory Investigation Of Aberrant Results:

We will cover the entire investigation in different parts and this one will be part-1.

After completion of the analysis, the analyst shall check the results. In case of aberrant results, the investigation shall be carried out in the following stages:

  1. Laboratory Investigation
  2. Process Investigation (Manufacturing Investigation)

Laboratory Investigation:

The first phase of such investigation should include an initial assessment of the accuracy of the laboratory data. The investigation should be done before the test preparations are discarded (wherever possible). This way, hypothesis regarding laboratory error or instrument malfunctions can be tested using the same test parameters.

If this initial assessment indicates that no meaningful errors were made in the analytical method used to arrive at the data, a full-scale investigation should be conducted.

The investigation shall cover the following points;

  • Analyst responsibilities and awareness
  • Analytical record review
  • Analytical method verification
  • Sample integrity
  • Reference/Working Standards
  • Laboratory chemicals and reagents
  • Laboratory equipments
  • Additional laboratory testing
  • Miscellaneous points

Let’s understand all points,

Analyst responsibilities and awareness:

The first responsibility for achieving laboratory testing results lies with the analyst who is performing the test. The analyst should be aware of the potential problem that could occur during the testing process and should watch for the problems that could create inaccurate results.

The analyst should check the data for compliance with test specifications before discarding the test preparations or standard preparations.

The analyst should not knowingly continue an analysis if the error or obvious reason is identified.

Discuss the test method with the analyst; confirm analyst knowledge and performance of the correct procedure.

Review the analyst qualification record for the qualification of the analyst to carry out the particular analysis. Crosscheck that the analyst is having sufficient knowledge and experience to perform the analysis.

Analytical Record Review:

Check that the complete raw data is available to perform the investigation. It should include the completely and correctly filled worksheet & raw data sheet, availability of the balance points wherever required & related printouts (Ex. UV scans, IR spectrums, Chromatograms, etc.)

Conformance to approved methods:

Check the raw data against the approved analytical method, for any deviation. check that all the instructions are being followed.

Ensure that the calculations are as per the approved analytical method & the values entered are correct.

Crosscheck the raw data with the supporting documents for correctness & accuracy. The data transferred should be free from any transcription error.

Laboratory Investigation Of Aberrant Results:
Laboratory Investigation

The remaining investigation parts of the laboratory investigation of aberrant results will cover in the next articles.

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