Europe – Update on the review of the CEP application regarding an impurity in the active substance paracetamol

The EDQM has concluded its investigation following reports that paracetamol manufactured by a specific company holding a certificate of suitability could be contaminated with the impurity 4-chloroaniline (PCA).

PCA is a known impurity which may be formed under certain conditions during the manufacturing process of paracetamol, and which should be removed or limited by a suitable control strategy. The levels of PCA reported by the media are well below the Acceptable Intake (AI) of 34 μg/day defined in the addendum of the guideline ICH M7 (Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk), even when using a high daily dose of paracetamol. In addition, no information is available about the analytical methods used to test the batches nor their validation…