Packaging
Advanced CCIT methods – such as headspace analysis and helium leak testing – provide precise, quantitative assessments of packaging integrity to meet stringent regulatory standards.
“In the case of syringes and cartridges, which have a movable stopper, problems can arise because you usually do not want to move the stopper during testing, as this alters the system one wants to characterise,” says Proff. “Pre-filled syringes or cartridges are both devices and primary packaging in one, which is not the case for a vial. Devices often come with an added complexity due to the several functions one component has in this combination.” “There are many criteria that determine test method selection,” he adds. “Are you using flexible or rigid packaging? Rigid packaging will not deform with pressure, but flexible packaging will. In a vial that has been closed there are no movable components, but the stopper in a syringe must move. Glass is not permeable to gas, but polymers will typically exhibit gas permeation over time. And with metallic materials, electric conductivity could lead to issues with tests identifying defects based on local changes in conductivity such as HVLD.”
The burden of choice
Overall, helium has one major advantage. Sample preparation is cumbersome, but the sensitivity level is high. But every CCIT technique has pros and cons, so there is no clear way to say that one is always preferable.
“So what do you optimise for?” asks Proff. “If you need to test lots of samples then perhaps use headspace, which can use an automated conveyor belt to present and test individual samples, one after the other, at very high speeds in on-the-market available configurations. The throughput is huge, so you could
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test an entire batch. Using helium means throughput is dramatically lower, but you extract potentially way more information regarding the performance of the CCS, which renders it very useful in CCS development to characterise a system’s properties with high sensitivity and short test cycles.”
The key is to understand early on the key risk criteria and develop a plan for CCIT along with the development of the product and the packaging. After all, different technologies see different things and identify different issues.
USP 1207 Package Integrity Evaluation – Sterile Products lists the recommended CCI testing methods for primary containers of sterile dosage forms. The last iteration was released in 2016. More recently, the European Union released the GMP Annex 1, which came into effect in 2023, mandating the use of a ‘statistically valid sampling plan’. This dismisses visual inspection alone as an acceptable test method, so more sophisticated CCIT methods are now required. “Testing must be considered right at the start of the development of the product,” stresses Proff. “You shouldn’t leave that decision to a late development stage, though that can happen. You must consider this as a priority task on the action item list early on, to define the best-suited CCI test method depending on product requirements and available packaging solutions, and if necessary change to more appropriate ones throughout the development process.” Late-stage CCI test failure in development could lead to a massive delay on the path to marketing approval. Whatever method is ultimately preferred, do not leave the choice to the last minute. ●
World Pharmaceutical Frontiers /
www.worldpharmaceuticals.net
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