RT Journal Article
SR Electronic
T1 Comparing Container Closure Integrity Test Methods—Performance of Headspace Carbon Dioxide Analysis versus Helium Leakage Using Positive Controls
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 681
OP 698
DO 10.5731/pdajpst.2023.012881
VO 78
IS 6
A1 Proff, Christian
A1 Victor, Ken
A1 Caudill, Allison Alix
A1 Nunkaew, Jirakan
A1 Bellavista, Gemma AlmatÓ
A1 RÖhl, Holger
A1 Veale, James
YR 2024
UL http://journal.pda.org/content/78/6/681.abstract
AB As described in USP <1207>, the deterministic leak test methods using laser-based gas headspace analysis and helium leakage are those with the highest sensitivities. As stated in the chapter, “no single package leak test or package seal quality test method is applicable to all product-package systems”; therefore, knowing the advantages and disadvantages of both of these techniques, and the extent to which they can be substituted for each other, is valuable. In an effort to begin addressing this issue, a systematic study using these two techniques has been performed. This study used the same well-defined positive controls prepared with microcapillaries for both measurement techniques. For the headspace gas analysis technique, the headspace carbon dioxide content was measured at multiple time points during three separate conditioning cycles using either a 0.5, 1.0, or 2.0 bar CO2 overpressure; the observed change in headspace carbon dioxide was then used to determine an ingress rate for each positive control. For the helium leakage technique, the positive controls were measured with a standard helium leak detector with 100% helium atmosphere on the atmospheric pressure side of the artificial defects. The resulting leakage rates from both techniques were compared for ingress into both ISO 2 R and ISO 10 R vials. The obtained correlation between helium and carbon dioxide leakage rates resulted in a minimum R2 coefficient of 0.98 across all 12 runs. Additionally, both setups met the acceptance criteria for accuracy with their respective calibrated standards.