Container Closure Integrity (CCI) Testing throughout the Product Life Cycle.
CCI testing plays an important role in maintaining the sterility and stability of sterile injectable products. Recent regulatory guidance and requirements are influencing changes in industry best practices for CCI testing. Emphasis is being put on implementing validated deterministic CCI testing methods and generating science-based CCI data.
LIGHTHOUSE offers solutions for CCI testing activities based on non-destructive laser-based headspace analysis. These solutions can be applied to various activities throughout the product life cycle in Development, Manufacturing and Quality Control.
Solutions for CCI testing activities
CCI Testing Method Development & Validation
An appropriate CCI test method should be applied for the specific product container closure system configuration used, the stage in the product life cycle, and the testing throughput required. LIGHTHOUSE offers robust analytical CCI testing method development, optimizing the method per customer product container configuration, demonstrating the detection of critical leaks with scientific studies, and determining limits of detection. Customers are supported with transfer and validation of the method through the provision of method validation protocols and on-site support with protocol execution.
Gas Ingress CCIT as Replacement for Blue Dye Ingress and/or Microbial Ingress testing
Imagine a blue dye ingress test but replace the dye with a tracer gas. Instead of visually inspecting containers to observe traces of blue dye and destroying valuable product, ingress of a tracer gas can be deterministically and nondestructively measured with a Headspace Gas Analyzer. Headspace Gas Ingress CCI testing is capable of generating robust analytical CCI data in all stages of the product life cycle. The non-destructive nature of the test and the generation of analytical data enables robust method development and validation of CCI test methods.
CCI during Deep Cold Storage & Transport
Certain sterile pharmaceutical products require deep cold storage, either at dry ice (-80°C) or even cryogenic (−196 °C) temperatures. Viral vaccines, gene therapies, or products that contain active cells (cell therapies) often need deep cold storage temperatures to maintain stability and/or activity. Such storage conditions pose a challenge to packaging components. It is therefore imperative that data is generated to demonstrate the maintenance of container closure integrity during deep cold storage and transport
Headspace Vacuum Maintenance
Some pharmaceutical formulations are sealed under (partial) vacuum to ensure proper reconstitution or to prevent interactions between the formulation and headspace gases. Regulatory guidelines require checking maintenance of vacuum in product containers over the shelf life of the product. Laser-based headspace analysis enables a rapid determination of the headspace pressure in sealed pharmaceutical product containers. Due to the nondestructive nature of the measurement, vacuum maintenance in samples can be followed over the entire product shelf life.
Qualification of Raised Stopper Limits
LIGHTHOUSE provides solutions for stopper height sensor qualification and validation of raised stopper limits. Scientific studies using laser-based headspace analysis can be executed to correlate the probability of CCI failure to raised stopper height. Raised stopper limits are determined for rejecting product at risk for loss of CCI.
CCI of Freeze-Dried Product
Freeze-dried product is often packaged with a modified atmosphere headspace consisting of a partial pressure of nitrogen. Therefore, a simple headspace oxygen measurement can be an optimum CCI test: detection of oxygen ingress identifies a CCI defective vial. The vial sealing process in the lyo chamber and extended time that a freeze-dried vial remains uncapped and uncrimped can introduce risk to the seal integrity of the container. A risk assessment may therefore conclude that CCI testing of freeze-dried vials is critical. 100% CCI inspection is often implemented in commercial production or for the re-work of CCI at risk batches.