Non-destructive vacuum decay method for pre-filled syringe closure integrity testing compared with dye ingress...

Area of Science:

• Pharmaceutical Technology
• Analytical Chemistry
• Regulatory Science

Background:

• Traditional sterility testing has limitations, prompting regulatory bodies like the FDA to encourage validated physical methods for container closure integrity testing (CCIT).
• Ensuring container closure integrity is critical for maintaining sterile drug product quality, safety, and shelf-life.
• Advancements in CCIT methods and equipment are driven by regulatory, quality, and safety expectations for sterile drug products.

Purpose of the Study:

• To evaluate the capability of four different CCIT methods in detecting simulated defects in glass prefilled syringes.
• To compare the performance of vacuum decay, pharmacopoeial dye ingress, Novartis specific dye ingress, and high-voltage leak detection methods.
• To identify the most effective, reliable, and repeatable CCIT method for prefilled syringe applications.

Main Methods:

• Development and validation of four CCIT methods: vacuum decay, pharmacopoeial dye ingress, Novartis specific dye ingress, and high-voltage leak detection.
• Creation of reference prefilled syringes with known defects (5 μm, 10 μm, 20 μm) using laser-drilled holes and embedded capillary tubes.
• Testing of syringes filled with sterile water and a flu vaccine (Agrippal) using validated commercial production equipment.

Main Results:

• The vacuum decay method demonstrated the highest performance in detecting defects, showing superior sensitivity, reliability, and repeatability.
• All tested methods were evaluated for their detection rates and false result percentages across different defect types and sizes.
• An innovative solution to prevent prefilled syringe plunger movement during CCIT was presented.

Conclusions:

• Vacuum decay is the most effective non-destructive method for ensuring prefilled syringe container closure integrity.
• This method reliably detects defects regardless of the fill substance (sterile water, drug product, or air).
• The findings support the adoption of advanced CCIT methods to meet stringent regulatory requirements for sterile drug products.