As Professor Schellekens points out, the complex high-molecular-weight three-dimensional structures of biopharmaceuticals, their heterogeneity and dependence on production in living cells makes them different from classical chemical drugs. Professor Schellekens: “Current analytical methods cannot characterise these complex molecules sufficiently to confirm structural equivalence with reference molecules. Verification of the similarity of biosimilars to innovator biopharmaceuticals remains a key challenge.”

Professor Schellekens claims that there is a need to comprehensively test biosimilars during the production process and always in comparison with an appropriate reference product. Although a variety of assays are available, they may not be adequate to reliably predict the safety and efficacy of a biosimilar product. “The validation and standardisation of assays will be crucial for future testing and regulation of biosimilars”, Professor Schellekens stresses. “The regulatory approval of biosimilars will require much more than the demonstration of pharmaceutical equivalence and pharmacokinetic bioequivalence associated with conventional generics.”

Professor Schellekens explains that the immunogenicity of recombinant therapeutic proteins has become a significant safety concern. “Ultimately, only clinical studies and post-authorisation pharmacovigilance to monitor potential immunogenicity will provide definitive evidence for product comparability to the innovator product with respect to safety and efficacy.”

Professor Schellekens underlines that, as manufacturing and clinical experience with the first biosimilar products accumulates, existing guidelines of the EMEA for the market approval of biosimilars will have to be revised to include the latest developments, while new guidelines will have to be developed for other biosimilar product classes.

Yet outstanding issues will need to be resolved, including substitution, naming and labelling of biosimilars. “Unique naming for all biopharmaceuticals would help to differentiate these products, facilitating accurate prescribing, dispensing and pharmacovigilance. A more transparent label with relevant European Public Assessment Report clinical data for the biosimilar would help clinicians make informed treatment decisions”, Professor Schellekens concludes.