Assessing developability early in the discovery process for novel biologics
Monica L. Fernández-Quintero,
Anne Ljungars,
Franz Waibl,
Victor Greiff,
Jan Terje Andersen,
Torleif T. Gjølberg,
Timothy P. Jenkins,
Bjørn Gunnar Voldborg,
Lise Marie Grav,
Sandeep Kumar,
Guy Georges,
Hubert Kettenberger,
Klaus R. Liedl,
Peter M. Tessier,
John McCafferty,
Andreas H. Laustsen
Affiliations
Monica L. Fernández-Quintero
Center for Molecular Biosciences Innsbruck (CMBI), Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, Austria
Anne Ljungars
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
Franz Waibl
Center for Molecular Biosciences Innsbruck (CMBI), Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, Austria
Victor Greiff
Department of Immunology, University of Oslo, Oslo, Norway
Jan Terje Andersen
Department of Immunology, University of Oslo, Oslo University Hospital Rikshospitalet, Oslo, Norway
Torleif T. Gjølberg
Authera AS, Oslo Science Park, Oslo, Norway
Timothy P. Jenkins
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
Bjørn Gunnar Voldborg
National Biologics Facility, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
Lise Marie Grav
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
Sandeep Kumar
Biotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA
Guy Georges
Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Penzberg, Germany
Hubert Kettenberger
Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Penzberg, Germany
Klaus R. Liedl
Center for Molecular Biosciences Innsbruck (CMBI), Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innsbruck, Austria
Peter M. Tessier
Department of Chemical Engineering, Pharmaceutical Sciences and Biomedical Engineering, Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA
John McCafferty
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK
Andreas H. Laustsen
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
ABSTRACTBeyond potency, a good developability profile is a key attribute of a biological drug. Selecting and screening for such attributes early in the drug development process can save resources and avoid costly late-stage failures. Here, we review some of the most important developability properties that can be assessed early on for biologics. These include the influence of the source of the biologic, its biophysical and pharmacokinetic properties, and how well it can be expressed recombinantly. We furthermore present in silico, in vitro, and in vivo methods and techniques that can be exploited at different stages of the discovery process to identify molecules with liabilities and thereby facilitate the selection of the most optimal drug leads. Finally, we reflect on the most relevant developability parameters for injectable versus orally delivered biologics and provide an outlook toward what general trends are expected to rise in the development of biologics.
