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.

Quality by design (QbD) approach in marketing authorization procedures of Non-Biological Complex Drugs: A critical evaluation.

The emergence of innovator-driven complex drug products, such as Non-Biological Complex Drugs (NBCDs), has provided disruptive advances in the Nanotechnology and Biotechnology fields. However, the design and development of NBCDs can be particularly challenging due to some unresolved scientific and regulatory challenges associated with the pharmaceutical quality assessment. The application of a more holistic, systematic, integrated science and risk-based approach, such as Quality by Design (QbD), is essential to address key scientific, technological, and regulatory constraints in the research and development of the NBCDs. The deeper product and process understanding derived from the implementation of the QbD approach ensures consistent, reliable, and high-quality pharmaceutical products. Furthermore, this approach promotes innovation and continuous improvement in the entire product lifecycle. Regulatory authorities highly recommend QbD-based submissions to successfully translate NBCDs from laboratory-scale research to the pharmaceutical market with the required quality, safety, and efficacy standards. The main aim of this article is to obtain a comprehensive and in-depth investigation into the state of implementation of the QbD approach in the pharmaceutical development and marketing authorization of NBCDs in Europe and the United States, through the analysis of the available data from their regulatory dossiers. In addition, it aims to understand and discuss how the QbD approach is used and implemented for complex drug products in the pharmaceutical industry, highlighting the gaps and challenges involved with its implementation. An analysis is held regarding QbD's advantages in terms of knowledge growth, regulatory flexibility, and the speed of development based on big data science, along with the reduction of regulatory failures and market withdrawals.