Laser-based Headspace Analysis (HSA) is an established technology that can be applied to various inspection tasks related to container closure integrity testing (CCIT) as well as process control. HSA is based on laser absorption spectroscopy and measures gas concentrations non-destructively in various package types such as vials, ampoules, syringes and also flexible packaging, for example IV bags and pouches.
Why Headspace Analysis?
The headspace inside a sterile pharmaceutical packaging is an integral part of the product according to USP1207 and therefore needs to comply with the corresponding quality relevant attributes. For oxygen sensitive formulations, the residual oxygen concentration is one of those attributes, while for lyophilizates the vacuum maintenance inside the container is another. In addition, changes of those values over time provide information on which other quality relevant attributes can be derived, such as integrity and stability.
Working principle of Headspace Analysis
Headspace Analysis is based on the principle of Tunable Diode Laser Absorption Spectroscopy (TDLAS) which is an infrared single-line absorption spectroscopy. The HSA system consists of a semiconductor laser and a sensor. A laser beam passes through the headspace of a sample and the absorption caused by the gas molecules is measured. The lasers can be tuned to different wavelengths allowing the measurements of different gases which absorb the laser. The amplitude of the measured absorption line is proportional to the concentration within the headspace. The main applications are based on the concentration measurement of oxygen (O2), carbon dioxide (CO2), or the total pressure, based on the measurement of water vapor (H2O).
As HSA is non-destructive and it can be used for the manual testing of individual samples as well as for fully automated testing at production speeds. Wilco introduced the first automated high-speed HSA system in 2003 and has continuously improved the technology with the goal for faster measurements, higher sensitivity, robustness and smaller footprints.
With the latest generation of lasers which was introduced in 2019, a new level of sensitivity has been reached. Standard deviations could be reduced by 50% in comparison with the previous generation allowing even more applications for small oxygen levels.
O2 Headspace Analysis
For oxygen measurements the laser is tuned to a wavelength of 760 nm. At this wavelength oxygen molecules absorb the laser and the reduction of the same provides information about O2 concentrations or the O2 partial pressure.
The O2 HSA systems are mainly used for container closure integrity testing. Oxygen sensitive pharmaceutical products are, in most cases, closed with a nitrogen overlay. In the case of a leakage, the oxygen level in the sample increases, due to the incoming air, which can then be detected by the HSA system. Even the smallest leaks can be detected given enough waiting time and preconditioning of the sample.
Another application for the oxygen measurement may be for the detection oxygen concentration changes due to the growth of micro-organisms, e.g. during media fills.
Your benefits
- Permanent and temporary leaks may be detected
- Short measuring times (less than 3 seconds)
- Non-destructive test method for 100% inspection
- Versatile use in terms of packaging and product types and sizes
- HSA is a deterministic CCI test method acc. USP<1207>
CO2 Headspace Analysis
For the measurement of carbon dioxide the laser is tuned to the wavelength of approx. 2000 nm. At this wavelength carbon dioxide molecules absorb the laser and the reduction of the same provides information about CO2 concentrations, the CO2 partial pressure, and the total pressure.
Applications for CO2 measurements range from non-destructive leak detection with a pre-treatment of the samples using CO2 as a tracer gas (Bombing) or the detection of microbial growth causing CO2 concentration changes.
Your benefits
- CO2 measurements provide higher sensitivity than with other gases
- Instant feedback on microbial growth or product stability
- Non-destructive test method for 100% inspection
- Short measuring times (less than 3 seconds)
- Versatile use in terms of packaging and product types and sizes
- HSA is a deterministic CCI test method acc. USP<1207>
H2O Headspace Analysis
For the measurement of water vapor or the total pressure the laser is tuned to a wavelength of 1400 nm on which H20 molecules absorb the laser. Based on the line width of the reading the total pressure inside the sample can be derived.
The HSA- H20 system is mainly used for container closure integrity testing of containers closed under vacuum and the verification of vacuum levels after the lyophilization process.
Your benefits
- Non-destructive test method for 100% inspection
- Versatile use in terms of packaging and product types and sizes
- Deterministic test methods acc. USP<1207>
- Permanent and temporary leaks can be detected
- Highest measuring precision for best possible results
- Combination possibilities with other inspection technologies from us
Leak testing reimagined – flexible, precise, and Annex 1 compliant - HSA in combination with bombing
Whether for packaging development, method validation, transport stress simulation, or routine testing: the combination of the bombing method and headspace analysis (HSA) offers pharmaceutical manufacturers a reliable solution for leak detection up to the MALL criteria – deterministic, sensitive, and fully automatable.
The method is ideal for:
- Pre-filled syringes, cartridges, and vials sealed at ambient pressure
- Lyophilisates and viscous products where classic vacuum tests fail
- Transport and stopper movement simulations in accordance with the requirements of Annex 1
- The safe release of batches in the event of potential process deviations
→ Watch our video to see how the method works and what advantages it offers in practice.
Method development is key
HSA itself is a powerful technology, however it is just one part of the solution.
An intense method development is a crucial step in the implementation for each Headspace Analysis systems. Starting with a detailed analysis phase, we also support our customers with feasibility studies in order to design the best solution. With more than 18 years of experience in this field we have implemented a wide range of applications and also hold patents on some of them. As an example, the gas ingress as an indication for non-integer containers takes multiple days under atmospheric conditions. Therefore, Wilco developed and patented a process called “Bombing” by which this process is accelerated and therefore reduces the waiting times.
Our HSA portfolio
Our product portfolio ranges from single station HSA laboratory systems to tailor made high-speed inline solutions for 100% testing with speeds of up to 600 products per minute. Additionally, we offer solutions which combine HSA with other inspection technologies such as visual inspection and/or near infrared spectroscopy (NIRS). As well as the method development our related services include the preparation of standards traceable back to NIST-standards and positive control samples.
Looking for more information about our HSA capabilities?
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