Regulatory Science Approach in Pharmaceutical Development of Follow-on Versions of Non-Biological Complex Drug Products.

Scientific and technological breakthroughs in the field of Nanotechnology have been a driving force throughout the development and approval of Non-Biological Complex Drugs (NBCDs). However, the fast-growing expansion of NBCDs and the emergence of their follow-on versions have brought with them several scientific, technological, and regulatory challenges. The definition of NBCDs is still not officially recognized by the regulatory authorities, and there is no dedicated regulatory pathway addressing the particular features of NBCDs and their follow-on versions. The lack of clear and consistent regulatory guidance documents in this field, as well as, the inconsistency across different regulatory agencies, impact negatively on the acceptance and enormous potential of these drug products. Patient access to high-quality NBCDs follow-on versions may be compromised by regulatory uncertainty resulting from the use of different regulatory approaches across the globe, as well as within the same class of products. Accordingly, there is a real need to develop a specific regulatory pathway compliant with the complexity of NBCDs and their follow-on versions or, alternatively, make better use of available regulatory pathways. The main goal of the review is to deeply investigate and provide a critical overview of the regulatory landscape of NBCDs and follow-on versions currently adopted by the regulatory authorities. The dissemination of knowledge and discussion in this field can contribute to clarifying regulations, policies, and regulatory approaches to complex generics, thereby filling regulatory and scientific gaps in the establishment of therapeutic equivalence.