Riccardo Torosantucci
Laboratory Head Formulation Development

Co-author:
Till Bussemer 
Head Pharmaceutical Development Biologics

Sanofi-Aventis
Frankfurt am Main, Germany

Abstract

This short review aims to highlight the excipients which have shown to reduce the viscosity of monoclonal antibody formulations as well as the analytical techniques employed for measuring viscosity and rheological properties of protein solutions, mainly tested in the last decade. In addition, preliminary results on high throughput, low volume, relative viscosity measurements of monoclonal antibody formulations via extrinsic steady state fluorescence are presented.

INTRODUCTION

With more than 52 approved monoclonal antibody (mAb) based products and a world-wide market forecast of $125 billion by 2020, mAbs represent the fastest growing class of therapeutic proteins, which finds several applications in the treatment of autoimmune diseases, oncology, metabolic disorders as well as in diagnostics (1-3).

Despite their high target specificity, therapeutic efficacy of mAbs is mostly reached at doses higher than 1 mg/kg (4).
Depending on the route of administration and on the therapeutic indication, application of these high doses can be achieved by injecting intravenously large volumes (> 10mL) of relatively low active pharmaceutical ingredient (API) concentrations (10-50 mg/mL). Alternatively, the protein concentration can be substantially increased above 100 mg/mL, in order to deliver a limited volume subcutaneously.
Most of the marketed mAbs are currently administered in hospital settings via the intravenous (i.v.) route, employing large volume bags.
This, however, requires several hours of hospitalization and trained personnel, besides having the risk of systemic infections (5).