Abstract

Pharmacopoeias, as standard references for pharmaceutical drug specifi cations and reference standards in the form of monographs, play a pivotal role to assure drug quality and safety. With emphasis on the activities concerning non-biological complex drugs (NBCDs), the mechanisms by which new monographs are introduced into the European and the US pharmacopoeias are presented.

 

Introduction

Over the last decades we came to realize that high molecular weight drugs of biological origin, such as therapeutic antibodies, are of a highly complex structure, which determines their activity as well as safety in terms of immunogenicity. The manufacturing of such therapeutics requires highly complex and meticulously controlled up- and downstream processes. Still, the final drug product whose properties are determined by the process is characterized by a certain degree of ‘microheterogeneity’, i.e. the presence of several isomers of the active pharmaceutical ingredient (API).

‘Follow-on’ protein therapeutics will not be manufactured by the same process proprietary to the originator. As the process itself determines the properties, e.g. microheterogeneity, of the final drug product, an originator protein therapeutic and its follow-on product may not be considered to be identical. Hence, the generic principle applied for drugs of low molecular weight, whose properties and composition are well defined and can be reproduced by generic drug producers, cannot be applied to complex drugs such as therapeutic proteins. A regulatory strategy leading to marketing authorization of follow-on biologicals in Europe and by the US Food and Drug Administration (FDA) – the ‘biosimilar’ pathway – has thus been established and refined. This approach includes elements such as clinical testing of the follow-on against the originator product in clinical trials, as well as post-marketing surveillance [1].

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