The authorization of non-biological complex drugs (NBCDs) follow-on versions: specific regulatory and interchangeability rules ahead?
Journal Title: Generics and Biosimilars Initiative Journal - Year 2013, Vol 2, Issue 4
Abstract
Introduction: Besides biologicals, a new class of complex drugs – non-biological complex drugs (NBCDs), e.g. liposomes, iron carbohydrate products and glatiramoids – has emerged. Originator NBCD products have been approved by established regulatory rules. However, their follow-on products comprise a challenge to the regulators, manufacturers, physicians and pharmacists. Methods: An expert panel at a closed workshop during FIP (International Pharmaceutical Federation) Centennial Congress 2012 discussed non-clinical and clinical aspects that distinguish NBCDs from traditional, small molecule drug products as well as new approaches for regulatory evaluation of NBCD follow-on products. Results: The active ‘substance’ of an NBCD is of non-biological origin and comprises a heteromolecular mixture of closely related, often nanoparticulate, structures that cannot be fully characterized physicochemically by state-of-the-art analytical means. The composition, quality, and in vivo performance of NBCDs are highly dependent on the manufacturing processes of both the active ingredient and the formulation. Furthermore, pharmacokinetics and pharmacodynamics can be substantially influenced by underlying diseases (particularly in case of associated inflammation). The abridged pathway for regulatory assessment of small molecule generics is not appropriate for NBCD follow-on products whereas the biosimilar pathway is not applicable to non-biologicals. Conclusions: New regulatory approaches for the approval of NBCD follow-on products that focus on advanced (analytical) technologies for in vitro characterization and on comparability of clinical safety and therapeutic efficacy are emerging. In contrast to generics, automatic interchange and substitution of NBCD follow-on products should be generally discouraged unless demonstration of therapeutic equivalence and similar safety profiles by appropriate studies.
Authors and Affiliations
Beat Flühmann, Jon SB de Vlieger, Arnold G Vulto, Stefan Mühlebach, Vera Weinstein, Vinod P Shah
Keywords
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- EP ID EP354772
- DOI 10.5639/gabij.2013.0204.054
- Views 85
- Downloads 0
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