Abstract

Preclinical studies have always been a critical component in the development program of a biopharmaceutical. With the advent of biosimilars the traditional preclinical program has changed to a new paradigm that integrates the concept of comparability with existing knowledge of the biopharmaceutical reference drug. Recently, the recommended preclinical program espoused by the European Medicines Agency has been modified to an abbreviated one that now emphasizes in vitro studies in lieu of in vivo for monoclonal antibody biosimilars. Likewise, the US FDA guidance on biosimilars suggests a flexible approach rather than the 28day comparative toxicology studies that have historically been conducted for worldwide marketing. For now, structure and function studies will continue to be the foundation of the overall analytical assessment of biosimilarity. Traditional, comparative animal safety assessments will have limited value in determination of biosimilarity and in an abbreviated design they may have most value in providing assurance of safety in ﬁrst-in-human trials when structural attributes are not indistinguishable. Unless this value can be proven, particularly as analytical technology improves in sensitivity, accuracy and precision, the need for these animal safety studies will diminish. Thus, the future lies in the ever evolving and sophisticated analytical studies that will replace the current in vivo studies for biosimilar products.

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Vol. 5, No. 5

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Published online 20 February 2013

Published in print March 2013

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Acknowledgements

The authors wish to thank S Knox of the European Generics Association for consultation and writing assistance regarding the legal intricacies of the EU’s biosimilar legislation.

Financial & competing interests disclosure

M Rogge is employed by Biogen Idec and through this affiliation is engaged in the development of both innovative and biosimilar products. A O’Connor works on biosimilars as an independent scientific and regulatory consultant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Nonclinical development of a biosimilar: the current landscape

Abstract

References