Process Development For Lyophilized Products

By Jayasree M. Srinivasan, Ph. D.

A typical strategy for developing processes for lyophilized products involves thermally characterizing the solution formulation to identify the critical product temperature that must not be exceeded during primary drying. This characterization is performed using differential scanning calorimetry (DSC) and freeze-dry microscopy (FDM). However, the development of the lyophilization cycle itself often lacks precision. Some scientists may adopt intentionally conservative conditions to prevent product failure during primary drying, which can result in unnecessarily long processing times that are inefficient for routine production. Alternatively, some may select shelf temperatures and chamber pressures for primary drying and conduct a limited number of experiments at temperatures and pressures close to these set points to establish an operating range. A significant challenge with both approaches is the inability to ascertain whether the process is operating close to the product's failure point, which can be catastrophic during scale-up to full production.

At Simtra, we approach formulation and process development with a focus on identifying these failure points. Understanding where the product may fail allows our development scientists to design formulations and processes with meaningful operational ranges supported by robust data. This document outlines Simtra's approach to process development for lyophilized products.