Container Closure Integrity (CCI) testing is a critical quality requirement for parenteral products, where even microscopic leaks can compromise sterility and patient safety. Regulatory agencies such as the FDA and guidance documents like USP <1207> emphasise the need for deterministic, validated CCI methods that provide consistent and measurable results throughout the product lifecycle.
Parenteral drug products, including injectables, biologics, and vaccines, present unique integrity testing challenges due to their complex container systems and stringent leak rate requirements. PTI addresses these challenges through its High Voltage Leak Detection (HVLD) technology, a non-destructive, deterministic CCI solution specifically designed for liquid-filled parenteral packaging.
Parenteral Products: Key CCI Testing Challenges
- Extremely Tight Leak Detection Requirements: Parenteral products require detection of leaks at the micron and sub-micron level. Conventional probabilistic methods, such as dye ingress or microbial ingress testing, often struggle to consistently detect defects of this size. These methods also lack quantitative outputs, making it difficult to establish clear detection limits.
- Complex Container Closure Systems: Parenteral packaging formats, including glass vials, pre-filled syringes, cartridges, and BFS containers, introduce multiple potential leak paths. Defects may occur at the stopper interface, crimp seal, plunger interface, or within the container itself. Accurately identifying these defects requires a technology capable of evaluating the entire container closure system.
- Destructive Testing Limitations: Many traditional CCI methods require destructive testing, which increases product waste and restricts sample sizes. Destructive approaches also prevent manufacturers from implementing 100% inspection and limit the ability to perform in-line testing during routine production.
- Regulatory Expectations for Deterministic Methods: Regulatory authorities increasingly favour deterministic CCI technologies that offer known sensitivity, reproducibility, and validated performance. Meeting these expectations using legacy methods often requires extensive justification and supplemental testing.
Non-Destructive CCI Testing Using PTI’s HVLD Technology
HVLD technology is a non-destructive and non-invasive Container Closure Integrity Test (CCIT) method that utilises controlled voltage characteristics to inspect a wide range of parenteral products, including complex combination products. The technology is suitable for pre-filled syringes, vials, cartridges, ampoules, BFS containers, bottles, and pouches.
The HVLD test method accurately detects and localises defects such as pinholes, micro-cracks, stopper or plunger leaks, non-visible leaks beneath crimp seals, and other integrity failures that may compromise sterility. To verify container closure integrity, the system scans a sealed, non-conductive container using precision electrode probes. When a defect is present, a change in electrical resistance occurs, altering the current flow and allowing the system to identify the breach.
Unlike conventional high-voltage leak detection approaches, PTI’s HVLD technology operates at significantly lower voltage levels, using approximately 50% less voltage and exposing the product and surrounding environment to less than 5% of that applied voltage. This reduced exposure minimises potential product risk while also significantly lowering ozone generation during testing. As one of the most sensitive deterministic CCI technologies available, PTI’s HVLD solution is particularly well suited for high-risk parenteral and combination product applications.
Benefits of PTI’s HVLD Technology for Parenteral CCI Testing
- Non-Destructive, Automated Inspection Capability: PTI’s HVLD technology enables full-unit inspection without damaging the product, allowing manufacturers to implement 100% testing while reducing waste and improving batch-level confidence.
- Deterministic, High-Sensitivity Detection: The technology delivers quantitative, repeatable results with sensitivity at the micron level. Clearly defined detection limits, supported by validated positive controls, strengthen method validation and regulatory submissions.
- Production-Ready and Regulatory Aligned: HVLD supports automated testing in manufacturing environments and aligns with USP <1207> expectations. Its deterministic performance simplifies validation, system suitability testing, and ongoing integrity verification while reducing operator dependence.
Conclusion
CCI testing for parenteral products demands technologies that deliver high sensitivity, repeatability, and regulatory compliance without compromising product integrity. Traditional destructive and probabilistic methods often fall short of meeting modern industry and regulatory expectations.
PTI’s High Voltage Leak Detection (HVLD) technology provides a proven, non-destructive, deterministic solution for liquid-filled parenteral packaging. By enabling high-sensitivity leak detection, scalable to be fully automated, and strong regulatory alignment, PTI’s HVLD systems help pharmaceutical manufacturers strengthen sterility assurance, reduce risk, and maintain product quality throughout the product lifecycle.