Pharmaceutical vials are small bottles or containers designed for parenteral administration (injection or infusion) in a single patient for a single case, procedure, or injection. They offer the highest Container Closure Integrity (CCI), which is a measure of how well a container protects the pharmaceutical ingredient against contamination by a variety of factors such as moisture, air, and chemicals.
In pharmaceutical manufacturing, the leak test is a critical parameter for vials. A visual inspection process may not detect defects that cause a sterile vial to leak. Thus, the pharma companies move toward CCI test methods. Many manufacturers are not sure how to conduct a container closure integrity test, but parenteral product leak testing is very important to assure that the product remains sterile in the packaging configuration throughout the duration of the product's shelf life.
What is CCIT?
Container Closure Integrity Testing (CCIT) is an important quality control technique for pharmaceuticals. It is an assay that evaluates the container closure and its capacity to keep possible contaminants out. Microorganisms, reactive gases, and other chemicals are examples of potential contaminants. This test is necessary for parenteral products since the seal quality is crucial to the drug product's sterility and quality throughout its shelf life. Inadequate sealing can accelerate the expiration of a drug product and cause significant risk to the patient's health if the product loses its sterility.
Previously, sterility testing was used to demonstrate container integrity. However, due to the insensitivity and other challenges associated with sterility tests, a variety of container closure integrity tests were developed. MicroCurrent HVLD, Vacuum Decay, and Helium Leak Detection are some of them. We give a brief overview of the above pharmaceutical package testing methods that can be used for testing pharmaceutical vials.
Leak Testing Vials Using Various CCI Techniques
MicroCurrent HVLD Technology
High Voltage Leak Detection (HVLD) is a non-destructive Container Closure Integrity technology that is used to evaluate the closure integrity of parenteral product packaging. HVLD technology makes use of quantitative electrical conductivity and resistance principles. The technology works by transmitting high voltage microcurrent impulses through sample packages. The electrical resistance of the sample lowers in the presence of a leak, resulting in an increase in current. HVLD technology relies on the “flow” of current, while other leak detection methods rely on the flow of gas or liquid. The MicroCurrent HVLD lowers product voltage exposure to less than 5% of that experienced while testing with similar HVLD technologies. When compared to conventional HVLD systems, reducing exposure voltage not only eliminates any risk that the voltage provides to the product, but also significantly reduces Ozone formation during operation. MicroCurrent HVLD can be used to test for leaks in nonporous, rigid or flexible packages, as well as packages containing liquid or semi-liquid products.
Helium Leak Testing
Helium leak testing is the method of locating leaks in enclosed or sealed systems by utilizing helium as a “tracer” gas and measuring the concentration as it exits owing to leakage. The package is filled with helium and vacuumed in this method. A helium leak detector is used to determine how much helium leaks from the container. The outcome is expressed as a leak rate. Helium leak testing is used in product design, product quality studies, failure analyses, and validation, in addition to being an effective container closure integrity test technique. Helium leak testing ensures high sensitivity leak detection, which is not achieved by many other leak test methods.
Vacuum Decay Technology
Vacuum Decay is a deterministic Container Closure Integrity testing methodology that relies on package integrity and leak path detection. Unlike human inspection and other non-deterministic testing techniques, Vacuum Decay provides quantitative and reliable test results to assure package integrity. Vacuum Decay technique can handle a wide range of package types, including filled and sealed rigid, semi-rigid, and flexible packaging comprised of nonporous or porous materials. This test involves placing packages in an evacuation test chamber with an external vacuum source. Vacuum levels are regularly monitored to detect deviations from a predetermined intended vacuum level. A defect in the packaging will allow air to escape into the test chamber. Packages with no defects, on the other hand, maintain a steady chamber vacuum level. Over the years, Vacuum Decay technology has proven to be one of the most practical and sensitive vacuum-based leak detection technologies.
Historically, dye immersion and microbiological immersion were the two most popular methods for leak testing vials. Recently, the USP has issued guidelines requiring the use of deterministic methods in order to produce more consistent and predictable results. USP<1207> recommends that dye immersion tests are avoided and HVLD or Vacuum Decay tests are used instead.