Freezing Bottles – 5 Critical Considerations

When freezing drug substances in bottles, success in biopharma depends on more than just reaching ultra-low temperatures; it hinges on protecting critical quality attributes like product safety and consistency. Uncontrolled freezing can lead to cryoconcentration, causing $\text{pH}$ shifts and protein denaturation due to the "volcano effect" where solutes are pushed to the center. To avoid this, a controlled freezing rate and temperature profile are essential.

Container integrity is equally vital. Single-use bottles, while seemingly rigid, become brittle in sub-zero conditions, making protection of the assembly crucial to prevent contamination. The method matters, too: blast freezers offer rapid, uniform cooling superior to static storage freezers, minimizing thermal gradients. Finally, considering bottle type and size (e.g., HDPE vs. PETG) and ensuring an end-to-end aseptic closed system from filling to thawing are the gold standards for quality and operational efficiency.

Access the full article to learn how to implement these five critical considerations for securing your drug substance quality during freezing.