Description du projet
Une nouvelle approche fait progresser le processus de développement de médicaments
De nouveaux produits pharmaceutiques à base de protéines et en particulier des anticorps font leur apparition pour le traitement de différentes maladies. Compte tenu de la taille, de l’hétérogénéité et de la complexité des molécules de protéines, leur caractérisation détaillée et leur analyse de pureté dans la cadre d’un processus de découverte de médicaments ont soulevé un défi technologique. Les chercheurs du projet LCxLCProt, financé par l’UE, proposent de développer une méthode basée sur la chromatographie pour la caractérisation des protéines biopharmaceutiques. Cette nouvelle méthode convient pour une utilisation au stade initial du développement du médicament et ensuite pendant la fabrication, à des fins de contrôle de qualité. Elle soutient les bonnes pratiques de fabrication et donc la confiance des consommateurs dans les produits pharmaceutiques.
Objectif
Protein biopharmaceuticals, which globally represent about 20 % of the total pharmaceutical market, are becoming increasingly popular in the treatment of various diseases. Experts forecast that over 50 % of new drug approvals in the next decade will be for biologics, especially monoclonal antibodies. Very accurate structural characterization and purity analysis is required during both the development of the new drugs, and later during manufacturing for quality control purposes. Biopharmaceutical protein molecules are very large and heterogeneous, which makes their characterization very difficult. The goal of this project is to develop novel methods for the characterization of protein biopharmaceuticals at the protein level based on comprehensive two-dimensional liquid chromatography (LC×LC). Two approaches will be explored: the use of reversed phase separation mechanism in both dimensions with parallel gradients, and application of thermally responsive stationary phases for thermal modulation of LC×LC fractions. Parallel gradients provide the greatest orthogonality when the separation mechanisms in both dimensions are correlated, and allow the use of short modulation periods, which together lead to a dramatic increase in peak capacity (as demonstrated in preliminary experiments). Thermally responsive stationary phases allow trapping of the analyte bands at elevated temperatures, and their release at low temperature. This is compatible with intact protein analysis, especially when ion exchange is used in the first dimension of the LC×LC system. It is expected that the research will result in new, cutting edge methods for the analysis and characterization of protein biopharmaceuticals that will be applicable under the good manufacturing practice (GMP) conditions, improving the quality assurance/quality control and increasing the confidence in the pharmaceuticals.
Champ scientifique
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MSCA-IF-EF-ST - Standard EFCoordinateur
9000 Gent
Belgique