Abstract

Since 2005, the European Medicines Agency (EMA) has published several guidelines laying down the regulatory framework for biosimilars approval. Based on the experience gained over these years, some initial guidelines are being revised to adapt them to the production of more complex biosimilar medicinal products. Nowadays, the adoption by the Committee for Human Medicinal Products (CHMP) of two concept papers on the revisions of the first biosimilar guideline and the guideline relating to non-clinical and clinical issues of biosimilar is pending. Likewise, the first revision of biosimilars guideline on quality issues has been drafted. Nevertheless, while new guidelines do not come into effect, applicants should follow the guidelines in force. This article reviews the studies needed for the development comparability exercise for biosimilars at quality, non-clinical and clinical levels according to the EMA regulatory guidance.

INTRODUCTION

Patents of some biotechnology-derived medicines (e.g. therapeutic proteins and monoclonal antibodies) have expired or will soon expire allowing their biosimilars market access (table 1). Marketing approval of copies of low molecular weight drugs (generic) only requires demonstration of chemical identity and bioequivalence regarding the innovator drug. However, in the case of biosimilars, the existing legal framework for generics does not apply. The difference in the legal requirements relies on the fact that biosimilars are similar but not identical to the innovator product while generics contain exactly the same active ingredient as the original drug (1,2).
Generic drugs are produced through physical and chemical methods, which results in a high degree of homogeneity. On the contrary, obtaining biosimilars involves differences in complex processes and biological materials regarding the original drug. The quality of the resulting biological is dependent on careful control of manufacturing processes. These processes have inherent variability so that the products obtained can also be different compared to the innovator product. Variati ...