Quality Control Testing of Raw Materials, APIs, and Finished Products.
The Quality Control Testing of Raw Materials, APIs, and Finished Products sample should be tested in accordance with the work plan of the laboratory after completion of the preliminary procedures. If this is not feasible the reasons should be noted,
e.g. in the analytical worksheet, and the sample should be stored in a special place which is kept locked.
Specific tests required may need to be carried out by another unit or by a specialized external laboratory. The responsible person should prepare the request and arrange for the transfer of the required number of units (bottles, vials or tablets) from the sample. Each of these units should bear the correct registration number. When the analytical test report contains results of tests performed by subcontractors, these results should be identified as such.
Detailed guidance on official pharmacopoeial requirements is usually given in the general notices and specific monographs of the pharmacopoeia concerned. Test procedures should be described in detail and should provide sufficient information to allow properly trained analysts to perform the analysis in a reliable manner. Where system suitability criteria are defined in the method they should be fulfilled. Any deviation from the test procedure should be approved and documented.
Evaluation of Test Results
Test results should be reviewed and, where appropriate, evaluated statistically after completion of all the tests to determine whether they are mutually consistent and if they meet the specifications used. The evaluation should take into consideration the results of all the tests (all test data). Whenever doubtful (atypical) results are obtained they should be investigated. The complete testing procedure needs to be checked according to the internal quality management system.
When a doubtful result (suspected OOS result) has been identified, a review of the different procedures applied during the testing process is to be undertaken by the supervisor with the analyst or technician before retesting is permitted. The following steps should be followed:
(a) Confirm with the analyst or technician that the appropriate procedure(s) was (were) applied and followed correctly;
(b) Examine the raw data to identify possible discrepancies;
(c) Check all calculations;
(d) Check that the equipment used was qualified and calibrated, and that system suitability tests were performed and were acceptable;
(e) Ensure that the appropriate reagents, solvents and reference substances were used;
(f) Confirm that the correct glassware was used; and
(g) Ensure that original sample preparations are not discarded until the investigation is complete.
The identification of an error which caused an aberrant result will invalidate the result and a retest of the sample will be necessary.
Doubtful results can be rejected only if they are clearly due to an identified error. Sometimes the outcome of the investigation is inconclusive — no obvious cause can be identified — in which case a confirmatory determination is to be performed by another analyst who should be at least as experienced and competent in the analytical procedure as the original analyst. A similar value would indicate an OOS result. However, further confirmation using another validated method, if available, may be advised.
An SOP should be in place for the conduct of an investigation of an OOS test result. The SOP should give clear guidance on the number of retests allowed (based on sound statistical principles). All investigations and their conclusions should be recorded. In the event of an error, any corrective action taken and any preventive measure introduced should be recorded and implemented.
All individual results (all test data) with acceptance criteria should be reported. All conclusions should be entered on the analytical worksheet (see Part three, section
by the analyst and signed by the supervisor.
WHO good practices for pharmaceutical Quality Control laboratories.
Guideline elaborated by the US Food and Drug Administration (5); Guideline elaborated by the European Network of Official Medicines Control Laboratories (OMCL) (28).