Formulation Design for Freeze-Drying: Case Studies of Stabilization of Proteins

Formulation design is an integral part of drug product development for parenterally applied dosage forms. In particular for freeze-dried formulations, the choice of excipients is crucial and directly influences lyophilization cycle performance and ultimately the product quality. The current chapter focuses on the development of freeze-dried protein formulations, such as monoclonal antibody formulations. Vaccines, oligonucleotides, and gene and cell therapeutic products are not within the scope of this chapter. Typical excipients for parenteral freeze-dried biopharmaceuticals and their functions are summarized and examples of recent commercial formulations are provided. The stabilization mechanism during freezing and thawing, molecular dynamics in the solid state, critical quality attributes and the link between product attributes and lyophilization cycle performance are discussed, and general rules for lyophilization dependent on formulation parameters are exemplified in case studies.