Nanoparticle iron medicinal products – Requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies

Currently, most countries apply the standard generic approach for the approval of intended copies of originator nanoparticle iron medicinal products, requiring only demonstration of bioequivalence to a reference medicinal product by bioavailability studies. However, growing evidence suggests that this regulatory approach is not appropriate. Clinical and non-clinical studies have shown that intended copy preparations of nanoparticle iron medicinal products can differ substantially from the originator product in their efficacy and potentially in their safety profile. An adapted regulatory pathway (separate from the standard generic approach) with defined data requirements is needed for approval of intended copies of iron medicinal products. Here, we discuss the difficulties involved in assessing therapeutic equivalence of nanoparticle iron medicinal products and suggest key concepts of a regulatory approach. Standardized non-clinical comparative studies are necessary but, as demonstrated in the reported clinical data, they may not be sufficient to demonstrate a comparable efficacy and safety profile. Validated, prospective, comparative clinical studies might be needed, in addition to non-clinical studies, in order to enable appropriate assessment of therapeutic equivalence. Furthermore, including brand names in addition to the International Non-proprietary Names (INNs) in safety reports could enable effective safety monitoring of intended copies and originator products.

► Efficacy/safety of complex medicinal products intended copies differs from originator product.
► The generic approach is not appropriate for approval of complex medicinal products.
► Need for a regulatory pathway for (non-)clinical evaluation of such products.
► Clinical data to provide proof of therapeutic equivalence and interchangeability.
► Brand names to be used in safety reporting to enable monitoring of intended copies.