Process cycle development of freeze drying for therapeutic proteins with stability evaluation

Many therapeutic proteins have been launched in market or gone into development stages for their high therapeutic efficacy. The proteins can be developed mainly as liquid or solid dosage forms; pre-filled syringes or freeze-dried. Regardless of the dosage forms, they have several stability issues due to the intrinsic properties of the proteins, which can have adverse effects on their efficacy such as loss of bioactivity and immunogenicity. In order to achieve enough stability of proteins, a solid-state dosage form, freeze-dried, has been preferred as providing a better shelf-life. Freeze drying process has become an important method to manufacture, store, and distribute the protein drug products. Despite its advantages, the freeze drying process still has challenges of stability issues and requires optimization. This review provides a basic concept of the freeze drying process while highlighting several stability issues encountered during the development of freeze drying cycle for protein formulations. Furthermore, various excipients used to stabilize freeze-dried protein formulations are also introduced.