Nanoparticle iron medicinal products – Requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies

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

“…Drug development and regulatory approval require distinct product naming, characterization and use of the specifi c product in preclinical and clinical evaluation of a product, see Figure 1 [11]. While relatively straight forward for small molecule generics, the required unequivocal identifi cation of the drug product can be impossible for NBCDs and their copies.…”

“…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]. …”

Nanotherapeutics in the EU: an overview on current state and future directions

“…57,58 These formulations are used when iron supplements given orally cannot be used or fail to provide therapeutic effect. Parenteral iron formulations have been widely used since the 1930s to treat iron-deficiency anemia in patients with chronic kidney disease.…”

“…64 Significant pitfalls have surfaced during the development of nanosimilar colloidal iron-based formulations with respect to the innovator product. 58 Differences in tissue distribution and toxicological profiles have been observed among nanoparticle iron formulations that have different carbohydrate coatings. When differences in the toxicological profiles were observed for nanoparticle iron formulations with the same coating, they were ascribed to the differences in the manufacturing process.…”

Complexity in the making: non-biological complex drugs (NBCDs) and the pharmacopoeias

“…iron sucrose products ('iron sucrose similars, ISSs'), and 'generic' Doxil (approved by FDA in 2013 in view of drug shortages in the US) have entered the market under the generics paradigm, partially due to the absence of a more suitable regulatory evaluation process. Therefore, an effort is needed to discover these correlations between nano-properties and biological activity, develop suitable analytical techniques and defi ne specifi cations, establish clinical protocols and, last but not least, integrate this knowledge in a science-based regulatory approach to nanomedicines [3].…”