Case Study on Manufacturing Scalability: Gelation Impact on Lyophilization

Manufacturability and scalability of a pharmaceutical/ biologic product is the ultimate goal for any formulation scientist. However, process transfer and scale-up are frequently complicated by the combination of product and process complexities due to the structural complexity of peptide molecules. Physical instability due to crosslinking or gelation behavior is particularly common among peptide therapeutics, creating significant challenges during product and process development.

While formulation approaches involving surfactants and stabilizers can mitigate gelation to an extent, such tailored solutions often delay translational research outcomes. For investigational peptides and protein therapeutics, many sponsor companies have been employing strategic solutions like lyophilization to accelerate development through Phase 1 clinical studies. Though lyophilization is widely established for creating stable peptide and protein formulations, the impact of inherent gelation behavior on primary drying rates and cycle times remains critically important for successful manufacturability.

This presentation will examine the relationship between peptide gelation characteristics and process parameters across different manufacturing steps to plan for a successful scale-up. This presentation will discuss a case study of an injectable product development of an investigative peptide molecule using lyophilization cycle development and studies to understand the impact of gelation on heat transfer during the primary drying phase (sublimation step).

Case study will help understand this fundamental interplay between gelation kinetics and lyophilization parameters enabling more efficient technology transfer from laboratory to clinical manufacturing. This also emphasizes importance of developing robust cycles that maintain consistency despite equipment differences across scales.