title: The Application of Noninvasive Headspace Analysis to Media Fill Inspection.
abstract: The results of a proof-of-principle study demonstrating a new analytical technique for detecting microbial growth directly in pharmaceutical containers are described. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to nondestructively determine gas concentrations in the headspace of a media-filled pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. Once aerobic microorganisms begin to divide after the lag phase and enter the exponential growth phase, there will be significant consumption of oxygen and concomitant production of carbon dioxide in the sealed container. Laser-based headspace analysis can accurately measure these changes in the headspace gas composition. The carbon dioxide and oxygen measurement data for the representative microorganisms Staphylococcus aureus, Bacillus subtilis, Candida albicans, and Aspergillus brasiliensis were modeled using the Baranyi-Roberts equation. The mathematical modeling allowed quantitative comparisons to be made between the data from the different microorganisms as well as to the known growth curves based on microbial count. Because laser-based headspace analysis is noninvasive and can be automated to analyze the headspace of pharmaceutical containers at inspection speeds of several hundred containers per minute on-line, some potential new applications are enabled. These include replacing the current manual human visual inspection with an automated analytical inspection machine to determine microbial contamination of media fill and pharmaceutical drug product vials.
  A novel analytical technique has been demonstrated for detecting microbial growth in media-filled pharmaceutical containers. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to determine gas concentrations in the headspace of a pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. The study shows that once aerobic microorganisms begin to grow after the lag phase and enter the exponential growth phase there will be a significant consumption of oxygen in the sealed container as well as a corresponding production of carbon dioxide. Headspace analysis can accurately measure and monitor these changes in the headspace gas composition and could therefore be used to detect contaminated pharmaceutical containers. Because the technique can be automated to analyze hundreds of containers a minute on-line, there are opportunities for implementing a headspace inspection machine to perform automated inspection of media fills used to validate aseptic filling operations.
authors: Lighthouse Instruments BV, Amsterdam, The Netherlands; dduncan@lighthouseinstruments.com.
authors: Derek
authors: D
authors: Duncan
authors: Microbiological Consulting, LLC, Scarsdale, NY, USA.
authors: Tony
authors: T
authors: Cundell
authors: Lighthouse Instruments LLC, Charlottesville, VA, USA; and.
authors: Lauren
authors: L
authors: Levac
authors: Lighthouse Instruments LLC, Charlottesville, VA, USA; and.
authors: James
authors: J
authors: Veale
authors: Lighthouse Instruments BV, Amsterdam, The Netherlands;
authors: Suzanne
authors: S
authors: Kuiper
authors: Lighthouse Instruments BV, Amsterdam, The Netherlands;
authors: Ravi
authors: R
authors: Rao
mesh_terms: D015169:Colony Count, Microbial / Q000379:methods / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging / Q000379:methods* / Q000592:standards; D006801:Humans; D004364:Pharmaceutical Preparations / Q000592:standards; D000075082:Proof of Concept Study; D013211:Staphylococcus aureus / Q000254:growth & development; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations
keywords: Frequency modulation spectroscopy; Headspace analysis; Headspace carbon dioxide; Headspace oxygen; Media fill inspection; Microbial detection; Microbial growth; Microbiological test method