Besides leak testing, non-destructive Headspace Analysis (HSA) is used for applications such as Process Analytical Technology (PAT).
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).
Nitrogen purging verification
Being a non-destructive test method, HSA allows 100% control in production processes providing an instant feedback to critical process parameters, such as residual oxygen in vials. Oxygen sensitive products require nitrogen flushing prior to sealing in order to maintain product stability during its shelf life. With more complex, biological and oxygen sensitive drugs emerging , the nitrogen purging process becomes a critical parameter. With the use of HSA in-line, together with the filling and sealing process, an instant feedback on the residual oxygen at levels below 1% can be given, even at production speeds.
Vacuum maintenance
Lyophilized drugs in vials are closed under vacuum in order to allow the diluent to enter the container for reconstitution. For such products the vacuum is a quality relevant attribute that needs to be verified. The Annex 1 of the EU GMP requires testing of such after an appropriate, pre-determined period and during its shelf life. The total pressure measurement can be done using HSA. Measurements are performed non-destructively on a sampling basis as well as during a fully automated in-process control.
