RT Journal Article
SR Electronic
T1 The Application of Non-Invasive Headspace Analysis to Media Fill Inspection
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2015.006312
DO 10.5731/pdajpst.2015.006312
A1 Derek Duncan
A1 Anthony M Cundell
A1 Lauren Levac
A1 James Veale
A1 Suzanne Kuiper
A1 Ravi Rao
YR 2016
UL http://journal.pda.org/content/early/2016/02/02/pdajpst.2015.006312.abstract
AB 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 non-destructively 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 non-invasive and can be automated to analyze the headspace of pharmaceutical containers at inspection speeds of several hundred containers per minute online, 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.