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Apr 2021

Evaluating Container Closure Integrity of High-Risk Pharmaceuticals

Evaluating Container Closure Integrity of High-Risk Pharmaceuticals

The pharmaceutical industry is crucial to the health care system as they assure treatments that were unimaginable a few years ago. As the industry grows in importance, the techniques of primary packaging for pharmaceutical products, especially high-risk medicines have taken on new prominence.

Since many high-risk pharmaceutical products are filled and sealed in combination devices, it’s critical for manufacturers to ensure that the components function well together. Hence, design and distribution considerations are critical to both the drug and the container. Manufacturing inconsistencies and tolerance differences in packages containing multiple components are primary contributors to distribution issues. Often, such inconsistencies result in container closure failure, causing serious implications down the supply chain. For instance, glass vials and pre-filled syringes may not seal properly at critical fill-finish closure points. Such a failure can cause oxygen or other environmental contaminants to enter the product and compromise the efficacy of the drug in the barrel. At this point, it is critical to use the most precise leak testing method possible.

Why Container Closure Integrity testing is important?

As per the FDA- Food and Drug Administration, A container and closure system refers to "the entirety of packaging components that together contain and protect the product". In simple words, Container Closure Integrity testing can be understood as a leak detection test. CCI solutions include non-destructive package inspection technologies to ensure product sterility throughout the product’s lifecycle. CCIT plays a vital role in ensuring that the products are free from any possible contamination. Conventionally, probabilistic test methods like bubble tests, dye ingress and microbial challenge were extensively used in pharmaceutical package testing. Since it was found that such test results lacked accuracy and reliability, the United States Pharmacopeia (USP) released guidance in 2016 stating that deterministic methods are preferred over probabilistic test methods. With this new USP <1207> chapter guidance, manufacturers today rely on non-destructive alternatives like Vacuum Decay technology and Micro Current HVLD technology that ensure highly sensitive package integrity solutions.

1. Vacuum Decay technology: Vacuum Decay technology is a non-destructive container closure integrity solution capable of detecting leaks in nonporous, rigid or flexible packages. Vacuum Decay leak testing is conducted by placing a sample package in a well-fitting evacuation chamber, which is provided with an external vacuum source. The vacuum levels as well as the change in vacuum over a fixed test time are closely observed using single or dual vacuum transducer technology. Changes in vacuum level beyond a predetermined pass/fail limit indicate defects within the package. VeriPac Vacuum Decay series can non-destructively test packaging down to sub-micron leak rates - making it an excellent alternative to destructive testing methods.

PTI’s VeriPac 465, the latest addition to the vacuum decay series is a robust and reliable solution for testing pharmaceutical containers and parenteral products, achieving highly sensitive sub-micron leak detection. The VeriPac 465 is the most sensitive vacuum based technology on the market to-date.

Benefits of Vacuum Decay Technology:

  • Non-destructive, non-subjective, no sample preparation
  • Deterministic test method that provides quantitative results
  • Multiple package testing in a single test cycle
  • Economical with rapid return on investment
  • ASTM Test Method, FDA standard and USP 1207 Guidance

2. Microcurrent HVLD technology: Microcurrent HVLD is a unique High Voltage Leak Detection technology, highly effective across all liquid filled parenteral products. Its applications include liquid-based products ranging from extremely low conductivity sterile water for injection (WFI) to large molecule-based proteinaceous products with suspensions. Its ability to detect small pinholes, micro cracks and seal defects makes it an ideal choice for testing high risk pharmaceutical and parenteral products.

Benefits of PTI’s MicroCurrent HVLD technology:

  • Non-destructive, non-invasive, no sample preparation
  • Highly effective across all parenteral products, including extremely low conductivity liquids (WFI)
  • Ensure higher levels of accuracy and reliability in test results
  • Simplifies the inspection and validation process
  • Offline and 100% online inspection
  • Referenced in USP 1207 Guidelines
CCIT, container closure integrity testing, container closure integrity, vacuum decay technology, high risk pharmaceuticals, hvld
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