Regulatory considerations for generic products of non-biological complex drugs

The Non-Biological Complex Drug (NBCD) Working Group defines an NBCD as a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by physicochemical analytical means. There are concerns about the potential clinical differences between the follow-on versions and the originator products and within the individual follow-on versions. In the present study, we compare the regulatory requirements for developing generic products of NBCDs in the European Union (EU) and the United States (US). The NBCDs investigated included nanoparticle albumin-bound paclitaxel (nab-paclitaxel) injections, liposomal injections, glatiramer acetate injections, iron carbohydrate complexes, and sevelamer oral dosage forms. The demonstration of pharmaceutical comparability between the generic products and the reference products through comprehensive characterization is emphasized for all product categories investigated. However, the approval pathways and detailed requirements in terms of non-clinical and clinical aspects may differ. The general guidelines in combi-nation with product-specific guidelines are considered effective in conveying regulatory considerations. While regula-tory uncertainties still prevail, it is anticipated that through the pilot program established by the European Medicines Agency (EMA) and the FDA, harmonization of the regulatory requirements will be achieved, thereby facilitating the development of follow-on versions of NBCDs.

Automated summary

The Non-Biological Complex Drug (NBCD) Working Group defines NBCDs as medicinal products that are not biological medicines and have complex structures that cannot be fully characterized using physicochemical analytical means. This study compares the regulatory requirements for developing generic NBCDs in the EU and the US, focusing on nanoparticle albumin-bound paclitaxel (nab-paclitaxel) injections, liposomal injections, glatiramer acetate injections, iron carbohydrate complexes, and sevelamer oral dosage forms. It emphasizes the importance of demonstrating pharmaceutical comparability between generic and reference products through comprehensive characterization. While the approval pathways and requirements may differ, it is anticipated that harmonization of regulatory requirements will be achieved through collaboration between the EMA and FDA.