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Research ArticleTechnology/Application

The Application of Noninvasive Headspace Analysis to Media Fill Inspection

Derek Duncan, Tony Cundell, Lauren Levac, James Veale, Suzanne Kuiper and Ravi Rao
PDA Journal of Pharmaceutical Science and Technology May 2016, 70 (3) 230-247; DOI: https://doi.org/10.5731/pdajpst.2015.006312
Derek Duncan
1Lighthouse Instruments BV, Amsterdam, The Netherlands;
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  • For correspondence: dduncan@lighthouseinstruments.com
Tony Cundell
3Microbiological Consulting, LLC, Scarsdale, NY, USA
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Lauren Levac
2Lighthouse Instruments LLC, Charlottesville, VA, USA; and
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James Veale
2Lighthouse Instruments LLC, Charlottesville, VA, USA; and
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Suzanne Kuiper
1Lighthouse Instruments BV, Amsterdam, The Netherlands;
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Ravi Rao
1Lighthouse Instruments BV, Amsterdam, The Netherlands;
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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.

LAY ABSTRACT: 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.

  • Microbial detection
  • Microbiological test method
  • Media fill inspection
  • Headspace analysis
  • Headspace oxygen
  • Headspace carbon dioxide
  • Microbial growth
  • Frequency modulation spectroscopy
  • © PDA, Inc. 2016
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PDA Journal of Pharmaceutical Science and Technology: 70 (3)
PDA Journal of Pharmaceutical Science and Technology
Vol. 70, Issue 3
May/June 2016
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The Application of Noninvasive Headspace Analysis to Media Fill Inspection
Derek Duncan, Tony Cundell, Lauren Levac, James Veale, Suzanne Kuiper, Ravi Rao
PDA Journal of Pharmaceutical Science and Technology May 2016, 70 (3) 230-247; DOI: 10.5731/pdajpst.2015.006312

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The Application of Noninvasive Headspace Analysis to Media Fill Inspection
Derek Duncan, Tony Cundell, Lauren Levac, James Veale, Suzanne Kuiper, Ravi Rao
PDA Journal of Pharmaceutical Science and Technology May 2016, 70 (3) 230-247; DOI: 10.5731/pdajpst.2015.006312
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Cited By...

  • A Container Closure Integrity Test Method for Vials Stored at Cryogenic Conditions Using Headspace Oxygen Analysis
  • Comparing Container Closure Integrity Test Methods--Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
  • Container Closure Integrity Test Using Frequency Modulation Spectroscopy Headspace Analysis with Carbon Dioxide as a Tracer Gas
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More in this TOC Section

  • Mechanical Container Closure Integrity Test: A Method for Cartridge Systems
  • A Container Closure Integrity Test Method for Vials Stored at Cryogenic Conditions Using Headspace Oxygen Analysis
  • Best Practices for Microbial Challenge In-Use Studies to Evaluate the Microbial Growth Potential of Parenteral Biological Products; Industry and Regulatory Considerations
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Keywords

  • microbial detection
  • microbiological test method
  • media fill inspection
  • headspace analysis
  • Headspace oxygen
  • headspace carbon dioxide
  • Microbial growth
  • Frequency modulation spectroscopy

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