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The pharmaceutical industry requires deep cold storage for complex drug and biologic formulations, but traditional packaging may not endure these extreme temperatures, risking leaks and product degradation. The PTI LT add-on units for SIMS helium leak detectors provide advanced solutions, assessing package integrity at 0°C to -160°C. This allows manufacturers to identify defects and enhance their packaging to ensure reliability in deep cold storage conditions.

Key Challenges in Container Closure Integrity Testing

• Material Challenges: Elastomers and plastics may become brittle at low temperatures, compromising seals and the overall integrity of containers.
• Leakage Risks: Both primary and secondary seals are at risk of failure under extreme cold conditions.
• Testing Limitations: Conventional leak testing methods may not provide reliable results at low temperatures.
• Regulatory Compliance: It's critical to comply with USP 1207 and international standards to ensure packaging meets required quality benchmarks.
• Logistics and Transportation: Effective temperature control and maintaining packaging durability during transit are key to ensuring product integrity.

Ensuring Container Closure Integrity in Cold Storage

As the pharmaceutical industry continues to develop complex drug and biologic formulations, there is an increasing demand for deeper cold storage to maintain product quality attributes. Products such as cell and gene therapies or protein-based treatments often require storage at ultra-low temperatures, below -20°C, and may involve dry ice (-78.5°C) or liquid nitrogen (-200°C). Despite the sophistication of these products, their packaging systems, such as screw or crimp top vials, are traditionally designed and may not be adequately tested for such extreme cold storage conditions. At these low temperatures, materials like elastomers can become brittle, leading to potential leaks, especially at primary seal areas, such as between the elastomeric closure and the vial. These leaks are not typically detectable at room temperature, making it crucial to test container closure integrity (CCI) under cold conditions.

To address this challenge, PTI developed the LT Low Temperature Add -On Solutions, designed for use with PTI’s SIMS helium leak detectors. Various models are available depending on application and low temperature needs. This system integrates a temperature conditioning chiller, allowing for temperature monitoring and helium leak testing of packages down to -160°C. By providing a method for testing CCI at low temperatures, the LT enables manufacturers to make informed decisions on packaging design, assembly parameters, and performance at cold storage temperatures. This solution helps ensure that products remain sealed, stable, and effective during storage and distribution in cold chain environments.

Ensuring container closure integrity (CCI) for sterile products in cold storage is essential to maintaining product quality and safety. The increasing use of ultra-low temperatures in storage, particularly for biologics and gene therapies, requires advanced testing methods to detect potential leaks and material failures. PTI’s LT Test System provides a reliable solution for testing CCI at temperatures as low as -160°C, helping manufacturers optimize packaging design and performance. By adopting these technologies, companies can ensure product stability and integrity throughout the cold chain, from storage to transportation.

Ensuring that packaging maintains its protective role without any leaks or failures is essential for product safety and quality. Traditional methods, such as Vacuum Bubble and Dye Penetration tests, have long been used to assess the integrity of sealed packages. Advancements in testing technologies have led to the development of more sophisticated methods like SIMS 1915+, which offers enhanced sensitivity and reliability compared to these conventional techniques.

Traditional package integrity tests 

Traditional package integrity tests are commonly used in the packaging industry to ensure that products, especially sterile or sensitive ones, are protected during transportation and storage. The traditional tests include:

• Vacuum Bubble Test:

This test involves submerging the package in a liquid (often water) and applying a vacuum. If there's a leak, air bubbles will form at the site of the breach, making it possible to visually detect the failure.

• Dye Penetration Test:

In this test, a dye (usually a coloured liquid) is applied to the package and then observed for signs of leakage. If there is a flaw or hole in the package, the dye will penetrate through it, and this is detected visually.

Helium Leak Testing using SIMS 1915+

Seal Integrity Monitoring System (SIMS) 1915+ is the perfect choice for a helium leak detection solution. Packages can be quantitatively evaluated to levels significantly higher than the vacuum bubble and dye penetration test procedures when helium is used as the tracer gas. By offering direct comparison over a wide range of packing materials and kinds, production line settings, and stable storage conditions, this quantitative technique supports the full lifespan. Package design, tooling certification, manufacturing line setup, and ongoing product quality monitoring are all possible using SIMS 1915+. Every SIMS 1915+ helium leak testing apparatus is constructed in accordance with the requirements of the client. The sensitivity of the quantitative CCI assessments that SIMS 1915+ can perform on packages is as low as 1 x 10 -10 mbar L/s. SIMS 1915+ also offers a complete Data Integrity software package compliant with 21CFR Part 11 requirements.

Benefits of SIMS 1915+ 

• High Sensitivity: Detects leaks as small as 1 x 10^-10 mbar/L/sec, far surpassing traditional methods.
• Quantitative Leak Detection: Provides precise leak rate measurement for better quality control and analysis.
• Versatile and Comprehensive: Suitable for a wide range of packaging formats, including bottles, syringes, vials, and blister cards.
• Customization for Specific Needs: Tailored to customer specifications for packaging types and production environments.
• Enhanced Regulatory Compliance: Provides verifiable evidence of packaging integrity, ensuring compliance with industry regulations.

The SIMS 1915+ helium-based leak detection system represents a significant advancement in package integrity testing. With its high sensitivity, ability to perform quantitative leak detection, and compatibility with a wide range of packaging formats, SIMS 1915+ offers a more accurate, reliable, and efficient solution.