Next-Generation Nanomedicines and Nanosimilars: EU Regulators’ Initiatives Relating to The Development and Evaluation of Nanomedicines

Abstract

Over the last three decades many first-generation nanomedicines have successfully entered routine clinical use and it is now important for medicines regulatory agencies to consider the mechanisms needed to ensure safe introduction of 'follow-on' nanomedicine products, 'nanosimilars'. Moreover, drug regulators need to ensure that 'next'-generation nanomedicines enter clinical development and consequently the market in a safe and timely way for the benefit of public health. Here we review recent European Medicines Agency activities that relate to the effective development and evaluation of nanomedicine products while keeping patient and consumer safety at the forefront.

Iron sucrose – characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas

“…However, the synthetic IS complex (and iron carbohydrate complexes in general) comprises a macromolecular and nanoparticulate structure that may even exceed the complexity of some biologicals [38,99]. Accordingly, IS is no single substance that can be isolated or fully characterized, and the physicochemical and biological properties of IS preparations (e.g., structure of the iron core, complex stability, biodisposition and bioavailability of iron after infusion) can be affected by subtle differences in the multistep manufacturing process.…”

“…Therefore, IS might be considered as a nonbiological complex drug (NBCD) [38]. While the originator IS received regulatory approval based on clinically assessed efficacy and safety, regulatory assessment of follow-on products is subject to a lively discussion since the abridged pathway for small-molecule generics does not seem appropriate for follow-on products of a NBCD and the biosimilar pathway cannot be applied to nonbiologicals [39,99].…”

“…Accordingly, experts from academia, industry and regulatory bodies suggest a stepwise similarity approach that includes appropriate clinical and/or nonclinical studies that evaluate pharmacokinetics, pharmacodynamics and safety/ efficacy of a nonbiological complex drug's follow-on products in relevant patient populations [38,99,102,103]. As long as proof of therapeutic equivalence and similar safety profiles by appropriate studies is missing, interchange and automatic substitution between nonbiological complex drugs and their follow-on products should be discouraged [39].…”

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle

“…These results indicate that the polymer cytotoxicity of PID 118 -b-PLA 39 micelles can be negligible, which is consistent with the results of previous studies. 28,46,47 In the application, proteins in the blood may affect the micellar stability during their circulation. BSA was used to evaluate the effects of these serum proteins on micellar in vivo stability.…”

First Asia-Pacific educational workshop on non-biological complex drugs (NBCDs), Kuala Lumpur, Malaysia, 8 October 2013

“…Therefore, authorities addressed the urgent need to defi ne best practices for nanosimilar approval and post-approval pharmacovigilance to maximize the chances that such follow-on products provide patients with non-inferior safety and clinical outcomes [4][5][6][7][8][9]. Recently, a nanosimilar approval approach has also been proposed [1,[10][11][12]. …”