Technology Introduction USP <1207> | Laser-Based Headspace Analysis

Laser-based headspace analysis is a means of assessing the partial pressure of a given gas molecule in the headspace of a product-package system. Headspace content changes can be driven by numerous variables, including poor manufacturing controls, product interference, and leakage. It is this concept of evaluating changes in headspace content over time and with exposure to different test conditions that enables container closure integrity testing using laser-based headspace analysis.

Principle of Operation USP <1207> | Laser-Based Headspace Analysis

As stated in USP <1207>, a test is performed by first placing the test sample in a fixture designed for precise test sample positioning. A near-infrared (IR) diode laser light is passed through the headspace region the sample. Light is absorbed as a function of gas concentration and pressure, yielding test results.

Applications and Limitations USP <1207> | Laser-Based Headspace Analysis

Since headspace analysis is simply measuring a real-time product attribute, almost like taking the weight of a sealed sample on a balance, the applications of the technology are myriad. The ability to assess oxygen, CO2, water vapor pressure, and total pressure, expand capabilities. The unique ability to nondestructively evaluate gas ingress over time also means that headspace analysis is able to assess down to the maximum allowable leakage limit (MALL) of most products and can be integrated at multiple lifecycle stages.

The application of headspace analysis requires an in-depth understanding of the product-package system and its intended storage environments. Implementing a test for stability sample analysis can be different than qualifying the package system in package development, even if testing in both lifecycle stages is performed using headspace analysis as the method. A gas concentration or pressure differential must exist between the inside of the package tested and the storage or conditioning environment.

For example, a sample filled with air, even with a large defect, will show constant headspace measurements if stored in an air environment. However, if that same vial was filled with nitrogen, that defect would allow for a measurable increase in the package’s oxygen headspace content over time. Exploiting this is key to a successful headspace program. Sample conditioning chambers may be used to force test gases in or out of a package, such as CO2 used as a tracer in Lighthouse Instruments’ test vessel. Another notable application is evaluation of leakage caused by cold storage conditions including dry ice CO2 and liquid nitrogen environments.

The team at CS Analytical consists of founding members of the world’s first cGMP, FDA-registered contract CCI laboratory housing all deterministic technologies as listed in USP <1207>. The resulting laboratory set standards and best practices for industry still used today, many of which are directly incorporated into USP <1207>. CS Analytical is the most trusted source for advisory services on CCI method selection, and developing and validating methods using state-of-the-art Lighthouse Instruments FMS headspace analysis systems that represent the cutting edge of best practices. New and expanding applications of headspace analysis make it a key component of CS Analytical’s platform.