Challenges and Considerations in the Development of a High Protein Concentration Lyophilized Drug Product

The lyophilized high concentration protein drug products have the advantages of product stability suitable for ADC and other stability sensitive molecules, speed to first-in-human clinical trials (shorter development time), and allowance for low-volume high-dose subcutaneous delivery of protein therapeutics. Successful development of a pharmaceutically and economically viable high protein concentration lyophilized drug product requires a solid understanding of the high protein concentration on the critical quality attributes and lyophilization process, as well as the implementation of an integrated approach for formulation and process development. In this chapter, we have discussed the scientific basis and unique challenges associated with the development of high protein concentration lyophilized drug products. Practical guidance for the successful development of high protein concentration lyophilized drug products and potential stability strategy for a lyophilized protein drug product stable for room temperature storage was also provided.