La gestion des OOS et la revue des audit trails au cœur de cette nouvelle injonction de l'US FDA

Cette injonction adressée à un site américain mentionne des manquements importants dans la gestion des OOS et de la revue des audits trails :

 1.    Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

 

From January 1 to June 30, 2016, your firm invalidated 101 out of 139 (about 72 percent) initial out-of-specification (OOS) assay results without sufficient investigation to determine the root cause of the initial failure.

 

For example, you opened laboratory investigation report PR 908027 for an initial OOS six-month stability assay result of (b)(4) percent (specification (b)(4)–(b)(4) percent) for (b)(4) mg tablets, lot (b)(4). You invalidated the initial failing result without adequate investigation, performed re-testing, and then reported the (b)(4) results of these replicate re-tests ((b)(4) percent). Your investigation did not reach an assignable cause, nor did you take appropriate corrective actions and preventive actions to ensure that the significant “analytical bias” to which you ultimately attributed the initial failure would not affect other analytical work in your laboratory....

2.    Your firm failed to establish an adequate quality control unit with the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a)).

 

Your quality unit failed to monitor and investigate error signals generated by the computerized systems that you use for high performance liquid chromatography and gas chromatography. These signals indicated the loss or deletion of original CGMP analytical data. However, your quality unit did not comprehensively address the error signals or determine the scope or impact of lost or deleted data until after these problems were reviewed during our inspection.

                                                   

For example, our investigator reviewed audit trails from August 2016 assay testing on (b)(4) batch (b)(4) and dissolution testing for (b)(4) tablets batch (b)(4). The audit trail for these tests included the message, “deleted result set,” but neither of these two incidents were recorded in the analytical packages for these batches of drug products, nor were they reviewed or investigated by the quality unit...

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