Regulatory Considerations, Challenges and Risk-based Approach in Nanomedicine Development

The translation of nanomedicines from the lab level into marketed product faces several challenges, including characterization of physicochemical properties, pharmacodynamics, pharmacokinetics, process control, biocompatibility, and nanotoxicity, scaling-up as well as reproducibility. The challenges of nanomedicine development are in connection with the different requirements from the patient (clinical and therapeutic use), industry (production), and regulatory bodies (authorization process). This paper aims at reviewing the status and regulatory aspects of nano-based drug delivery systems with a focus on the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) regulations. In addition to discussing the risks accompanied by the development of nanomedicine, the potential of following a risk-based methodology from the early stage of the R&D phase is emphasized here to ensure safety and efficacy when developing novel nano-based dosage forms. The R&D of nanomedicines is a complex and multidisciplinary approach, and there are still many challenges in their regulation and legislation. In general, the most critical considerations for nanomedicines are the product quality assessment (physicochemical characteristics, quality control, manufacturing process) and product safety assessment (pharmacokinetics, biodegradation, accumulation, and nanotoxicity). The paper presents a promising paradigm in the development and marketing authorization of nanomedicines, namely the Quality by Design (QbD) approach. Sufficient knowledge on the quality, safety, and efficacy of nanomedicines is necessary to obtain a significant focus on establishing robust, standardized methods for evaluating the critical quality attributes of nanomedicines. The QbD-based submission is highly recommended and required by the regulatory authorities, enabling a smooth clinical translation of the novel nanomedicines.