Ongoing Challenges to Develop High Concentration Monoclonal Antibody-based Formulations for Subcutaneous Administration: Quo Vadis?

Journal of Pharmaceutical Sciences, vol. 111, pp. 861–867

Abstract

Although many subcutaneously (s.c.) delivered, high-concentration antibody formulations (HCAF) have received regulatory approval and are widely used commercially, formulation scientists are still presented with many ongoing challenges during HCAF development with new mAb and mAb-based candidates. Depending on the specific physicochemical and biological properties of a particular mAb-based molecule, such challenges vary from pharmaceutical attributes e.g., stability, viscosity, manufacturability, to clinical performance e.g., bioavailability, immunogenicity, and finally to patient experience e.g., preference for s.c. vs. intravenous delivery and/or preferred interactions with health-care professionals. This commentary focuses on one key formulation obstacle encountered during HCAF development: how to maximize the dose of the drug? We examine methodologies for increasing the protein concentration, increasing the volume delivered, or combining both approaches together. We discuss commonly encountered hurdles, i.e., physical protein instability and solution volume limitations, and we provide recommendations to formulation scientists to facilitate their development of s.c. administered HCAF with new mAb-based product candidates.

Authors 5

1. Wim Jiskoot Aachen Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany; Leiden Academic Center for Drug Research (LACDR), Leiden University, 2300 RA Leiden, the Netherlands

   Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany

   Leiden Academic Center for Drug Research (LACDR), Leiden University, 2300 RA Leiden, the Netherlands

2. Andrea Hawe
   Affiliation as printed

   Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany

3. Tim Menzen
   Affiliation as printed

   Coriolis Pharma Research GmbH, Fraunhoferstr. 18 b, 82152 Martinsried, Germany

4. David B. Volkin

   University of Kansas

   Affiliation as printed

   Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS 66047, USA

5. Daan J.A. Crommelin corresponding

   Utrecht University

   Affiliation as printed

   Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands. Electronic address: d.j.a.crommelin@uu.nl

   Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, the Netherlands