Beyond Probability: Choosing Deterministic Methods for Container Closure Integrity Testing

Container closure systems are vital for maintaining the integrity and safety of drugs, which is especially crucial for biologic drugs due to their complexity and sensitivity. Throughout drug development, it’s essential to minimize the risk of failure, and the packaging that interacts with the drug is key in preserving its properties. Drug manufacturers must prove that their containers comply with regulatory standards set by the US FDA, EMA, and other global health authorities to ensure patient safety. Packaging suppliers can collect drug-independent data through deterministic or probabilistic container closure integrity testing to support their customer’s choice of packaging.

A probabilistic testing technique analyses a sequence of events that can happen either one after the other or at the same time, with each event associated with uncertainties depicted by probability distributions. Conversely, a deterministic leak testing method delies on predictable leakage events that can be detected with physicochemical technologies, making control and monitoring straightforward and providing objective, quantitative data.
Recently, regulatory agencies have promoted the use of deterministic methods for new products, with regards to their reliability and precise CCI measurements.

Antonio Scatena comments on a choice of deterministic CCI testing method; Vacuum Decay, High Voltage Leak Detection and Laser-Based Gas Headspace Analysis.

Vacuum Decay: this technique tracks vacuum levels and their changes over time. It works for many standard packages, like vials, ampoules, prefilled syringes, as well as flexible containers such as IV bags, lyophilized products, pouches, and eye squeeze droppers. The main benefits of this method are the absence of specific sample preparation, it’s rapidity, and non-destructive nature.

High Voltage Leak Detection: this technique assesses high voltage currents traversing potential leakage paths and is particularly effective for products with large molecules or high viscosity. It generally does not require sample preparation and is typically non-destructive.

Laser-Based Gas Headspace Analysis: this technique utilizes Frequency Modulation Spectroscopy (FMS) and is often combined with gas ingress to quantify the partial pressure of carbon dioxide or oxygen concentration in a product’s headspace. It functions optimally from ambient to cryogenic temperatures, enabling the identification of transient leaks and temporary defects that might arise during storage.

Selecting the appropriate CCI testing for a drug packaging configuration requires to consider several factors: the packaging specifications and nature, drug characteristics, storage conditions, and fill volume. Gateway Analytical, an Aptar Pharma company, is a cGMP certified lab specialized in analytical testing, providing advanced methodologies and a comprehensive range of instrumentation to meet regulatory expectations and accommodate a wide variety of customer situations. Choosing the right partner guarantees fast regulatory approval, accurate and reliable results, and adherence to strict customer quality standards, so that our pharmaceutical customer can accelerate and de-risk their drug development.