Low Temperature Storage Containment for Vial and Syringe Systems

Among the many sessions at the recent Parenteral Drug Association Week (formerly PDA Annual Meeting) in Palm Springs, CA, several focused on advanced therapy medicinal products (e.g., cell therapies, gene therapies), biosimilars, and disruptive therapies (e.g., live biotherapeutic products). With the growth of these therapies, there is an increased need for specialized low-temperature packaging solutions, particularly for vials and syringe systems at -50^oC to ≤ -130^oC.

Thermal Expansion, Volume Reduction, and Container Closure Integrity

When it comes to low-temperature storage, it must be considered that components for vial systems or pre-filled syringes that fit and function well at room temperature have different coefficients of thermal expansion and therefore see volume reduction at different rates when temperature is lowered. This raises concern about system breach and concomitant loss of container closure integrity (CCI) and sterility.

The systems need to maintain CCI at various temperatures (-50°C for vaccines, -80°C or dry ice for gene therapies, and below -130°C for cell therapies), as well as prevent adverse interactions and ensure recovery and viability of the products.

T. Page McAndrew, Ph.D., Director, Scientific Communications at West Pharmaceutical Services, Inc. addressed these issues in his PDA Week podium presentation last month, “Vial Containment and Syringe Systems for Low Temperature Applications.”

Demonstrate Suitability

The only way to demonstrate suitability of a vial system or pre-filled syringe is to test at the required temperature. An experimental approach (with selected use of accelerated conditions) that can be used for either system was presented, taking into account the following considerations:

•  Evaluation of CCI - headspace analysis over time (up to two years) examining for atmosphere exchange
• Evaluation of interaction ⁃ Extractables analysis for potentially deleterious compounds from elastomer component⁃ Examination of particle formation and product loss using protein models for potentially deleterious interaction with any component
• Evaluation of maintenance of virus and cell vitality (gene and cell therapies)
• Measurement of syringe plunger movement (i.e., position at points during low-temperature exposure and return to room temperature) to determine if sterile barrier is breached
• Evaluation of maintenance of acceptable initiation and sustaining forces after return to room temperature

Vial Systems

Suitability of a vial system was evaluated with:

• Daikyo Crystal Zenith® cyclic olefin polymer (COP) vials
• Borosilicate glass vials
• Elastomer stoppers with and without FluroTec™ poly(ethylene tetrafluoroethylene) barrier film laminated on the side facing drug product

Pre-filled Syringe Systems

Suitability of a pre-filled syringe system was evaluated with:

• Borosilicate glass barrelsPlungers with the same laminated
• FluroTec barrier film facing drug product

Key Observations: Vial Systems

• No breach: Regarding CCI, vial systems comprising COP vials and stoppers with FluroTec barrier film showed no breach over 2 years at either:
  • -80°C (no atmosphere exchange over one-year, small exchange over two years) or
  • -130°C (liquid nitrogen vapor – no atmosphere exchange over two years) 
• Stoppers with FluroTec barrier film demonstrated (when compared to non-laminated stoppers):
  • substantially reduced extractables level in both the number observed and concentration
  • substantially reduced interaction with protein models
• COP vials demonstrated (as compared to borosilicate glass vials):substantially reduced interaction with protein models 
• Transducability:
  • with representative adenovirus, adeno-associated virus, and lentivirus, after low-temperature storage in vial systems comprising COP vials and elastomer stoppers with FluroTec barrier film, no loss of transducability was observed

Key Observations: Pre-filled Syringe Systems

With shorter term testing at -50°C, syringe systems saw no loss of CCI, maintained acceptable initiation and sustaining forces, and saw limited plunger movement that could be quantified to determine if there was an issue with sterile barrier breach.

Summary

Vial systems that included COP vials and stoppers with FluroTec barrier film showed very promising results and clearly merit consideration for any low-temperature application. These observations underscore the importance of appropriate low-temperature packaging solutions in the growth and effectiveness of advanced therapeutics.

If you work for an emerging company or are in the process of developing advanced therapy medicinal products including cell therapies, gene therapies, or biosimilars and biotherapeutic products that require specialized low-temperature packaging, read more about West Platform Test Methods and West’s Analytical Lab services to mitigate your risks and get to market faster.

FluroTec is a trademark of West Pharmaceutical Services, Inc. and used under license from Daikyo Seiko, Ltd.