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In pharmaceutical packaging, choices made early in development often shape the performance and longevity of the final product. Packaging must protect contents from contamination, moisture, and leakage, especially when dealing with sterile or sensitive drug formulations. Early-stage container closure integrity (CCI) testing provides a structured approach to evaluating how well packaging systems maintain a sealed environment. By introducing CCI testing at the start of the design process, manufacturers can gather valuable insights about materials, formats, and sealing methods—allowing designs to be refined before they become fixed in later phases.

Why Early-Stage CCI Testing Matters?

Early-stage CCI testing creates opportunities to explore different packaging configurations before a final design is selected. It helps determine how well closures, seals, and materials perform under different conditions, including pressure variations, temperature exposure, and storage durations. By introducing testing at this point, it is possible to detect possible leak paths or inconsistencies without the time and cost impact of post-production fixes.

This early insight can reduce delays during regulatory filing and product validation by demonstrating how the package maintains its protective function over time. It also supports quality-by-design approaches by enabling packaging development to progress alongside product formulation, rather than as a separate or delayed activity.

CCI testing at the development stage is especially valuable for products requiring long shelf lives, or sterile delivery. It helps evaluate whether packaging choices will continue to perform reliably throughout their intended use, without relying solely on visual inspections or assumptions.

Integrating CCI Testing into Packaging Development

To apply CCI testing during development, several non-destructive technologies are available. Methods like vacuum decay, pressure decay, Microcurrent HVLD and airborne ultrasound can be applied during packaging studies to evaluate different container formats or sealing techniques. These methods can detect micro-leaks that would go unnoticed with conventional inspection techniques. Analytical methods such as Helium are applied for R&D CCI testing of pharmaceutical products (syringes, vials, cartridges). Common applications include component and material evaluation including low temp testing.

Vacuum Decay Technology

Vacuum Decay is a widely adopted, non-destructive technology for detecting leaks in pharmaceutical packaging. Recognized by the FDA and defined by ASTM Test Method F2338, it offers a sensitive and reliable approach to verifying container closure integrity. During testing, the package is placed in a sealed chamber connected to a vacuum source; once evacuated, sensors track pressure changes over time. A consistent vacuum indicates an intact seal, while any variation suggests a leak—even at a microscopic level. PTI’s VeriPac series uses this method to identify sub-micron leaks with precision, making it a preferred alternative to traditional techniques. Integrating Vacuum Decay leak testing into production helps manufacturers identify defects early, reduce product loss, and maintain high packaging quality standards. This approach ensures that only properly sealed, contamination-free products are released to the market, supporting product stability, patient safety, and regulatory compliance without damaging the tested units.

MicroCurrent HVLD Technology

MicroCurrent High Voltage Leak Detection (HVLD) is a non-invasive method for testing liquid-filled pharmaceutical containers such as pre-filled syringes, vials, ampoules, cartridges, and BFS bottles. It is effective across various formulations, including low-conductivity sterile water and protein-based biologics. The process involves scanning sealed containers with electrode probes that apply a low electrical current. An intact container allows a consistent current path, while any defect disrupts the flow, indicating a leak. Unlike traditional HVLD systems, MicroCurrent HVLD uses about 50% less voltage, reducing stress on products and minimizing risks to sensitive formulations. Operating with less than 5% of the voltage typically used, it offers a safer testing approach without compromising sensitivity. This makes it a reliable choice for maintaining container integrity in parenteral and biologic drug packaging.

Airborne Ultrasound Technology

Airborne Ultrasound technology is a non-destructive and precise method for evaluating seal quality in flexible pharmaceutical packaging. Standardized by ASTM Test Method F3004 and recognized by the FDA, it uses high-frequency sound waves transmitted through the seal to detect defects. As the ultrasound passes through, consistent signal patterns indicate intact seals, while disruptions reveal issues like voids, leaks, or weak spots. This approach allows for accurate detection of seal defects that visual inspection might miss. Its sensitivity and reliability make it a valuable tool for maintaining package integrity and ensuring product safety without damaging the tested items.

Helium Technology

Helium is a highly sensitive leak test technology, specifically designed for the detection of extremely small leaks and tortuous pathways which is not possible with any other leak testing methods. Using a high vacuum technique, the leak test thresholds can be set down as low as 1×10-10 mbar L/sec, a sensitivity level allowing unique comparisons between package components, materials selection, and production controls, for example.

Helium leak detection methods utilize a highly sensitive mass spectrometer detector to accurately evaluate each sealed package/system type. A vial, consisting of a container (glass or plastic) and elastomeric closure, is a good example of a package system. A vial can be helium-filled & and then subjected to vacuum pressure. Any amount of helium escaping from that vial container is quantitatively measured and stated as a leak rate (flow rate) expressed in mbar L/sec.

Starting CCI testing early in the packaging lifecycle provides valuable information that supports design improvements, faster development, and stronger product protection. By applying this testing while packaging formats are still flexible, potential issues can be identified and addressed before they grow into more complex challenges. This approach improves the overall reliability of pharmaceutical packaging and contributes to product success from development through delivery. Instead of reacting to failures, early-stage testing supports packaging strategies built on real data and performance under relevant conditions.