Implementing enhanced lyophilized cycling for a stable drug product

With so many factors to consider, developing a lyophilization process can be complex. A customer approached Enzene Biosciences for the development of a lyophilization cycle to produce a stable drug product that remained safe and efficacious.

Lyophilization design must consider the following:

• pH: Screening of the pH from pH4 to pH8 enabled selection of the optimum pH7.
• Buffer: At pH7, three different buffers were studied and the best buffer was selected.
• Excipient: An array of excipients were screened to monitor the formation of an isotonic solution for both liquid and lyophilized formulations.
• Cycle development: Testing freezing and drying of both small-scale (10 vials) and full capacity (180 vials).

Despite having optimized the lyophilization process, a series of challenges were observed. This included incomplete sublimation resulting in melt back and aggregation of the product. Both hinder product quality and safety.

Through optimization of the primary drying temperature, efficiency sublimation was enabled, overcoming the melt back issue. In addition, the use
of small-scale buffer exchange performed at 2-8°C via centrifugation filtration mitigated the risk of aggregates by helping to stabilize the drug product.

Having optimized lyophilization and overcome obstacles, Enzene Biosciences developed an effective and efficient process, leading to a stable drug product for the customer.