Parenteral protein formulations: An overview of approved products within the European Union

Abstract

The study presented is a comprehensive overview of commercial parenteral protein formulations, approved by the European Medicines Agency (EMA), 1995-2018. The objective of this overview was to analyse current trends in the design of commercial parenteral protein products and thereby support formulation scientists in the design of new formulations. The main data source was the publicly available European Public Assessment Reports (EPARs) published by the EMA for each authorised product. An analysis of the percentage of formulations in a liquid and lyophilised form was conducted. In addition, the number of products containing individual excipients, classified into functional categories is provided. Finally, the overview includes comprehensive details of product compositions obtained from EMA, US Food and Drug Administration (FDA) and product Marketing Authorisation Holder. Data analysis highlighted trends in the number of products approved, and the higher percentage of liquid parenteral protein formulations (66%) compared to lyophilised formulations (34%). This overview identifies the most commonly incorporated excipients employed as buffering agents, stabilisers/bulking agents, surfactants, preservatives and tonicifiers, including their concentration ranges of use in both liquid and lyophilised formulation approaches. Finally, antibody-based formulations were a particular focus of this overview. The relationship between parenteral routes of administration and antibody concentrations in approved products was also investigated.

Keywords: Antibodies; European Medicines Agency; Excipients; Formulation; High concentration; Lyophilisation; Proteins.