An update on the clinical evidence that supports biosimilar approvals in Europe

Abstract

AimSponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe.MethodsWe used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars.ResultsThe high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars.ConclusionsEuropean regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided.

Type and Extent of Information on (Potentially Critical) Quality Attributes Described in European Public Assessment Reports for Adalimumab Biosimilars

“…Despite this variability in QA reporting, pCQAs were most frequently and consistently reported by EU regulators in EPARs. The variation in QA report-ing between EPARs is consistent with the variability in reporting clinical data, which was explained by the flexibility in regulatory requirements (i.e., a case-by-case basis) [43,44]. However, such flexibility cannot explain the variability in reporting of QAs and pCQAs for biosimilars, particularly those containing the same active substance and compared to the same reference biological (e.g., Humira ® in the case of adalimumab), that were assessed based on the same regulatory standards for establishing biosimilarity.…”

“…The European public assessment report (EPAR) is an unbiased source through which the EMA publishes and broadcasts information to stakeholders about regulatory assessments for all medicinal products approved by the European Commission (EC) [37]. Previous studies have provided an in-depth overview of the clinical evidence reported in EPARs that supports approval of biosimilars in general [43,44] and approval of adalimumab biosimilars in particular [45]. These studies have shown that variations exist in reporting clinical data that confirm the biosimilarity of biosimilars to a reference biological, but they have not explored the reporting of the QAs that are the basis of biosimilar approval.…”

The controversy around technical standards for similar biotherapeutics: barriers to access and competition?†

“…15 It has also been documented that both the FDA and the EMA have approved less complex therapeutic proteins via abbreviated pathways. 3,16 The adoption of this simplified and pro-competitive approach in the global south would be facilitated if WHO amended its guidelines, instead of brand names reduces information asymmetry. 17 The use of INN on prescription, dispensation, labels, and pharmaceutical advertising is part of WHO's ethical criteria for medicinal drug promotion.…”

“…The EMA is moving slowly to revise the comparability paradigm, as commented before, 7 and some middle‐income countries, like Colombia and Brazil, have allowed simplification or even waivers of confirmatory trials in specific circumstances, too 15 . It has also been documented that both the FDA and the EMA have approved less complex therapeutic proteins via abbreviated pathways 3,16 …”

Use of a two‐sided tolerance interval in the design and evaluation of biosimilarity in clinical studies

“…Recently, biological products have been used in therapies for certain cancers and rare diseases 1 . Due to complications in the development of these macromolecular medicines, the prices of innovative biological products are always high.…”