Retrospective Validation

Retrospective validation could be conducted for a well-established process that has been used without significant changes (e.g., changes in raw materials, equipment, systems, facilities, or in the production process) that affect the critical quality attributes of the API. This validation approach should be used only when there is sufficient history on past API batches to demonstrate the process consistently produces acceptable products, and where: - Critical quality attributes and critical process parameters have been identified and documented; - Appropriate in-process specifications and controls have been established and documented; - There have not been excessive process/product failures attributable to causes other than operator error or equipment failure unrelated to equipment suitability; and - Impurity profiles have been established for the existing API.

In addition to the information described in Section XIII.B., the validation protocol should include the batch selection criteria and analytical data that will be evaluated to determine consistency of the process.

The number of batches to review will depend on the process, but, in general, data from 10 to 30 consecutive batches should be examined to assess process consistency. The review should include any batches that failed to meet specifications. All batches within the selected review period should have been manufactured by the same process and have the same documented history of controls and tests as current APIs. Additional testing of retained samples may be warranted to obtain the necessary data to retrospectively validate the process.

Data obtained should be evaluated by appropriate personnel, and a final validation report summarizing the results and appropriate conclusion should be prepared. This report should be reviewed and approved by the organizational units that approved the original protocol.

Retrospective validation could also be employed to provide additional data to supplement prospective validation and either build confidence in a particular manufacturing process or impugn it as test results are received.