Residual product moisture content is a critical parameter when considering the stability and shelf life of lyophilized pharmaceutical product.  Consequently, moisture analysis is performed in product and process development, as well as in commercial manufacturing to specify and control the maximum allowable moisture content.  This is traditionally performed using Karl Fischer titration or thermo-gravimetric analysis (TGA) methods, which are destructive and labor & time intensive.  Replacing these slow traditional methods with a rapid non-destructive method would streamline moisture analysis efforts and help improve the quality of finished product.

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Laser-based headspace analysis utilizing frequency modulation spectroscopy (FMS) is a rapid analytical method used for the analysis of finished sterile drug product.  Quantifying the amount of water vapor in the headspace of freeze-dried vials with an optical method enables rapid non-destructive moisture determination.  Experiments have demonstrated that the amount of headspace water vapor directly correlates to the lyo cake moisture content.  Stability studies have shown that the degradation of the active pharmaceutical ingredient correlates to the initial water vapor concentration present in the freeze-dried vial.

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In some cases, the freeze dried formulation is also sensitive to oxidation.  Unfortunately, existing analytical methods for monitoring oxygen in the headspace of parenteral containers are slow and/or destructive. Conventional destructive techniques, such as electrochemical methods or gas chromatography, are time and resource intensive. In addition valuable product is destroyed and costs are incurred as a result of the destruction and disposal of analyzed samples.

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In contrast, the laser-based headspace method for oxygen analysis is a rapid measurement technique resulting in efficient stability studies and requires no specialized operator expertise.  The non-destructive nature of the measurement saves QC product samples that may be in limited supply and allows for the accurate monitoring of the oxidation of a single sample over time.