Amino acid misincorporation in recombinant biopharmaceutical products.

Microbial and mammalian host systems have been used extensively for the production of protein biotherapeutics. Generally these systems rely on the production of a specific gene sequence encoding one therapeutic product. Analysis of these protein products over many years has proven that this was not always the case, with multiple species of the intended product being produced due to amino acid misincorporation or mistranslation during biosynthesis of the protein. This review is the first to give a comprehensive overview of the occurrence and analysis of these misincorporations. Furthermore, using the latest data on misincorporation in native human proteins we explore potential considerations for producing a specification for misincorporation for the development of a human biotherapeutic protein product in a production environment.