Freeze Drop Testing of Bulk Drug Substance Bottles

Importance of the Topic

Ensuring the integrity of bulk drug substance containers under cryogenic conditions is critical to prevent product loss and maintain bioprocessing quality. Routine freezing below minus 70C can induce flash freezing which often leads to undetected structural failures in conventional bottles.

Objectives and Study Overview

This study evaluated the performance of four one liter bottle types made of PFA ETFE PETG and PC. All bottles were frozen to minus 85C for at least 24 hours and subjected to a drop test from 36 inches onto a concrete surface. Structural integrity was assessed before and after thawing.

Methodology

• Seven bottles of each material from the same production lots were selected
• Bottles were sterilized by gamma irradiation or autoclave for PFA
• Each was filled to 1000 mL with water and closures torqued to manufacturer settings
• Freezing was performed at minus 85C for 24 hours
• Drop tests were carried out from 36 inches onto concrete in both bottom and side orientations
• Inspections for cracks leaks and paneling were conducted immediately after drop and again post thaw

Used Instrumentation

• Commercial upright freezer rated to minus 85C
• Calibrated dial torque wrench for closure tightening
• Gamma sterilizer and laboratory autoclave

Main Results and Discussion

• PFA and ETFE bottles showed no damage or leak before and after thaw confirming excellent cryogenic performance
• All PETG bottles exhibited significant cracking and failed on initial impact indicating poor suitability for cryogenic handling
• PC bottles mostly survived however one failure occurred due to a polypropylene closure shattering at cryogenic temperature

This demonstrates that matching container and closure materials based on cryogenic compatibility is essential

Benefits and Practical Applications

Fluoropolymer bottles provide robust containment for sensitive biologics and bulk drug substances at very low temperatures. They reduce risk of product loss during storage and handling and simplify quality assurance and quality control protocols in bioprocessing environments.

Future Trends and Possibilities

Continued development of single material container closure systems and exploration of advanced polymer composites could further enhance cryogenic storage reliability. Integration of leak sensors and adoption in automated biobanking are promising areas

Conclusion

This study confirms that PFA and ETFE bottles outperform PETG and PC alternatives in cryogenic freeze drop tests making fluoropolymer containers the preferred choice for secure bulk drug substance storage below minus 70C

Reference

Savillex Technical Note TN025 020920 Freeze Drop Testing of Bulk Drug Substance Bottles