Pharmaceutical issues and their impact on the efficacy and safety of biosimilar therapeutic products

Abstract

Patent expiration of originator chemical medicinal products led to the development of generics. In the case of biologics a new category of medicinal products referred to as biosimilars, approved on the basis of similarity to the reference products rather than bioequivalence, was introduced. Pharmaceutical issues during development and manufacture can affect the safety and efficacy profile of biosimilars. The aims were to identify, classify and analyse pharmaceutical issues encountered during development and manufacture of biosimilars, to assess differences in risk minimisation measures (RMMs) between biosimilars and their reference products, and to determine whether the safety and efficacy profile of biologics changed with the EU authorisation of biosimilars. The methodology consisted of analysis of the Committee on Human Medicinal Products Day 120 list of questions adopted during the quality module assessment of 22 biosimilars marketing authorisation applications. The Day 120 questions identifying pharmaceutical issues are classified as ‘Major Objections’ or ‘Other Concerns, collectively referred to as deficiencies. The frequencies of deficiencies were calculated and described. Review of whether any of these deficiencies impacted safety concerns and an analysis of RMMs related to biosimilars and their reference products was carried out. Changes in the safety and efficacy profile of biologics with the advent of biosimilars were explored via a data mining exercise of adverse events reported in Eudravigilance database using its inbuilt Eudravigilance Data Analysis System (EV DAS) for signal detection. Frequencies and trends of deficiencies were recorded for 22 biosimilar marketing authorisation applications. The study resulted in identification of 32 ‘Major Objections’ (mean 1.45, range 0-12 per application) and 1042 ‘Other Concerns’ (mean 47, range 44 131 per application). Analysis of RMMs of biosimilars and their reference products revealed no differences in safety risks. The data mining exercise of all adverse events associated with biosimilars and the reference products using EV-DAS signal detection (95% CI) did not show any confirmed signal of a changing safety and efficacy landscape. This study contributes towards an understanding of pharmaceutical issues related to biosimilars which can help improve registration dossiers. The study indicates that the introduction of biosimilars did not impact the safety and efficacy profile of biologics and that the EU regulatory framework safeguards the quality, safety and efficacy of biosimilars placed on the EU market.