FIONA M. GREER
SGS M-Scan Ltd, 2-3 Millars Business Centre, Fishponds Close, RG41 2TZ, Wokingham, Berkshire, United Kingdom

Abstract

Many countries have now established legal and regulatory pathways which allow manufacture of “copies” of a patent–expired biotherapeutic product. Companies developing these “copies” must demonstrate that they are similar by performing a side-by-side comparison with a reference sample of the originator molecule. There are many challenges – legal, regulatory, non-clinical and clinical – which manufacturers must rise above to develop biosimilar products for global markets. One of the first hurdles to be negotiated prior to biological and clinical testing is demonstrating physicochemical similarity to the originator. This task requires a thorough understanding of glycoprotein structure and appropriate and sensitive analytical techniques to probe it.

INTRODUCTION

Many of the first generation biotherapeutic products have reached, or are about to reach, patent expiry. This has led to the advent of “biosimilars” - legally approved versions of an existing branded biologic granted marketing approval on the basis of analytical, pre-clinical and clinical data which show they are highly similar to the original drug. A key driving force for this emerging pharma sector is the universal need for more affordable medicines. Indeed, the potential market for these products is forecast to be substantial; US$64 billion in global biologics sales will be off-patent by 2015. This article outlines some of the challenges involved in establishing “biosimilarity” using analytical techniques- the first of many steps required on the route to market.

SMALL MOLECULE GENERICS VS LARGE MOLECULE BIOSIMILARS
Biosimilar drugs cannot be regarded in the same way as generics. Unlike small, synthetic molecules, biologically-derived proteins are complex molecules, comprising of a mixture of closely related species. When produced in mammalian expression systems these proteins can also be glycosylat ...