Abstract
Non-Biological Complex Drugs (NBCDs) are complex non-biological drugs comprised of large high molecular weight molecules and, often, nanoparticular structures (including liposomes and block-copolymer micelles). In the case of NBCDs, the entire complex is the active pharmaceutical ingredient and its properties cannot be fully characterized by physicochemical analysis. Moreover, the manufacturing process is fundamental in creating the correct originator product. The same is true for generic versions of the product. A recent appraisal of approval procedures for NBCDs “follow-on products” approved in Europe shows a diversity of regulatory pathways. In fact, three different abridged application procedures, under European legislation, were used: the generic application procedure of Article 10(1), the hybrid application procedure of Article 10(3), and the biosimilar application procedure of Article 10(4). Three informed consent applications via Article 10(c) from innovator companies of glatiramer acetate and sevelamer carbonate were submitted shortly after the approval of the first follow-on products. Furthermore, a number of “well-established use” applications [via Article 10(a)] were approved for iron sucrose and iron dextran complexes. In order to protect patients from the increased risks of NBCD products and NBCD follow-on products, two complementary approaches should be considered: (i) improving the regulatory procedures and their guidance documents within the pre-registration phase, and (ii) not considering interchangeability whenever clinical data is not available. With regards to the latter, the need for adequate safety and efficacy data might also include risk management programmes within post-approval pharmacovigilance actions. This, however, would depend on a risk appraisal that must be considered for individual medicinal products, based on the nature of the submitted relevant set of safety/efficacy data.
Highlights
The current paper intends to be an expert-driven and fact-based. It was produced by a group of specialists in areas pertaining to the scientific issues, with significant experience in the development, regulatory review, and clinical use of non-biological complex drugs (NBCDs)
Previous work was done by a NBCD expert group established within the framework of TI Pharma in the Netherlands, with contribution from two of the current authors (RG and BS-L)
Even though we focus more on the European Union (EU) situation in the current text, we believe there are lessons to be learned that impact regulatory scenarios in different geographical areas and under different regulatory frameworks
Summary
Rogério Sá Gaspar 1,2*, Beatriz Silva-Lima 3,4, Fernando Magro , 5,6,7,8 Armando Alcobia 6,9, Fernando Leal da Costa 7,10 and José Feio 8,11. Three informed consent applications via Article 10(c) from innovator companies of glatiramer acetate and sevelamer carbonate were submitted shortly after the approval of the first follow-on products. In order to protect patients from the increased risks of NBCD products and NBCD follow-on products, two complementary approaches should be considered: (i) improving the regulatory procedures and their guidance documents within the pre-registration phase, and (ii) not considering interchangeability whenever clinical data is not available. With regards to the latter, the need for adequate safety and efficacy data might include risk management.
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