Uncompromised Container Closure Integrity at cryogenic temperatures

The robustness of the AT-Closed Vial®

Materials

The use of Cyclic Olefin Copolymer (COC) for the vial body and a proprietary Thermoplastic Elastomer (TPE) for the stopper ensures suitability for cryogenic temperatures with similar low temperature behavior

Manufacturing Process

Precise molding and robotic assembly with tight tolerances (±0.02 mm repeatability) ensures optimal fitting of the vial components

Gamma Irradiation and Chemical Bonding

Sterilization by gamma irradiation, combined with the compression between the stopper and vial body, creates a chemical bonding between the COC and TPE. This bonding plays a significant role in maintaining CCI at low temperatures.

Unique Filling Process

The vial is filled through the stopper with a sterile needle, which then mechanically recloses. A subsequent one-second laser shot re-seals the needle trace, and a sterile cap is added for protection. This process maintains a functionally closed system throughout filling, minimizing contamination risks, and ensures a restored CCI after F&F.

Testing and validation

Our whitepaper covers the extensive validation efforts that demonstrate the resistance of the AT-Closed Vial® to (ultra) cold temperature storage. These include:

  • Dye Ingress Tests: Demonstrating maintained CCI after long-term storage at various cryogenic temperatures (e.g., -80°C and in liquid nitrogen) for up to 15 months
  • Closure Integrity Tests at Different Conditions: Demonstrating that CCI remains intact even after four years of storage at various temperature) and relative humidity conditions
  • Laser Headspace Analysis (LHA): Studies using Frequency Modulation Spectroscopy exhibited no change in headspace oxygen levels or increased pressure in AT-Closed Vials stored in the vapour phase of liquid nitrogen (-165°C), indicating uncompromised integrity. In contrast, traditional glass vials with butyl stoppers exhibited significant leakage under the same conditions
  • Analysis of Chemical Bonding: Techniques like Scanning Electron Microscopy, Raman spectroscopy, and mass spectrometry confirmed material transfer and chemical bonding between the stopper and the vial body, contributing to CCI
  • Computed Tomography (CT) Scans: Visualising the maintained contact between the stopper and body of the AT-Closed Vial® at cryogenic temperatures, further supporting CCI
  • Helium leak test: ongoing testing

In conclusion, the AT-Closed Vial® technology offers a robust and validated solution for maintaining container closure integrity of cell and gene therapy products during cryogenic storage.

Its unique design, material composition, and manufacturing process, coupled with a closed filling system, address critical challenges in this rapidly evolving field. The extensive validation data supports its suitability for ensuring product quality throughout the lifecycle, making it a preferred choice for numerous sponsors in the cell and gene therapy. The ability to scale the filling process and adapt to different container sizes further enhances its utility for developers; different solutions are available to accommodate the needs from process development to commercial manufacturing.

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