What to consider for a good quality PDE document?

Abstract

For the handling of active pharmaceutical ingredients (APIs) and production of medicinal products in shared facilities, the European Medicines Agency (EMA) has introduced the determination of permitted daily exposure (PDE) values to provide limits for cross-contamination. APIs have a desired pharmacological effect in the patient who intendedly uses a certain medicinal product. However, this effect is undesired in a patient that receives this API unintendedly as a cross-contamination of another medicinal product. In particular, for approved APIs for human use, a multitude of data is available on the pharmacological activity as well as adverse effects, which have to be taken into account in PDE setting. Thus, the setting of PDEs for APIs needs a structured scientific evaluation of all properties and identification of the most critical effect, which is the basis for PDE calculation. In this publication, we provide guidance on points for consideration when setting PDEs for APIs, or when evaluating the quality of documents describing the derivation of PDEs received, e.g. by third parties.