Phase 1 Investigation and Phase 2 Investigation

In Phase I, the retained solutions are examined as part of the laboratory investigation. This helps to ensure that the error is not due to faulty equipment/instrument or testing process and involves:

• Re-injecting the Solution: This helps to establish whether the error is due to the malfunctioning of the instrument.
• Re-dilution or Re-pipetting of the Solution: This helps to eliminate dilution or pipetting as the cause for the error.

Documenting the investigation is another important component of Phase I investigation. In case of a cause is ascertained for the OOS during the investigation, it must be retested or recalculated. The results of the retest or recalculation must be documented and reported. If the results conform to the specifications the second time, then the initial data must be invalidated.

However, if a retest validates the initial results, then a full-scale OOS investigation should be performed using a predefined procedure.

In Phase II investigation, the components include:

• Review of production/manufacturing process: A thorough, timely, and well-documented review of the production, sampling procedures, and additional laboratory testing is conducted to identify the root cause.
• Testing Hypothesis/Experimentation: A document describing the testing process is readied, and investigational testing is initiated with the approval of the QA team.

The document must describe;

• The hypothesis for investigating the root cause.
• The samples to be tested.
• The execution process.
• The process of evaluating data.

Hypothesis testing is initiated after completing the Analyst and Supervisor investigation and can include the original working stock solutions but not another preparation from the original sample. The original preparation or working solutions can be re-measured. It can be re-injected where transient equipment is suspected of malfunctioning. This is especially useful in identifying a malfunctioning instrument as the root cause. For dilution error, re-dilution of the original Solution can help. Investigational testing helps to confirm a probable cause rather than eliminate a suspect.

• Additional laboratory testing: Phase II investigation may include additional laboratory testing that covers
• Resampling: A new sample is collected from the batch in case the original sample is insufficient for conducting the tests. The procedure to obtain the resample must be discussed and agreed upon by QA/Contract Giver/QA and recorded. The same qualified, validated methods as used for the initial sample must be used.

If the investigation reveals that the original sample was not appropriately prepared and therefore does not represent batch quality, a new and more accurate sampling method must be developed, documented, reviewed, and approved by the QCU.

• Retesting: Retesting should be performed purely based on sound scientific reasons and with approval. A second aliquot from the same homogeneous material as the original sample is tested by a second, more experienced, and qualified analyst.