Authors
Chaoying Ma, Minmin Zhang, Qiaoxia Shi, Shulin Zhang, Xinyi Zhou, Chunfang Xing, Sujuan Qin, Ing Hou Loh
Published in
PDA journal of pharmaceutical science and technology. Oct 23, 2026. Epub Oct 23, 2026.
Abstract
Vacuum decay is a pressure-based container closure integrity testing (CCIT) method inherently sensitive to ambient temperature and humidity. Even minor fluctuations in these environmental factors could produce measurable shifts in the differential pressure. Repeat measurements of a solid Master vial over one year showed that the differential pressure had moderate positive correlations with both temperature (ρ = 0.4044) and humidity (ρ = 0.4973). This sensitivity raises concerns about the robustness of pass/fail thresholds established under relatively fixed environmental conditions when applied across a wider operational spectrum.To evaluate the associated risks, two condition-specific thresholds were established. Despite following an identical development strategy within the same controlled laboratory setting, the resulting thresholds differed substantially: 120 Pa under relatively hot and humid conditions, versus 85 Pa under cool and dry conditions. Retrospective analysis of multi-seasonal historical data obtained from routine real-world quality control testing revealed a significant asymmetry in performance: application of the 120 Pa threshold produced false negatives, whereas the 85 Pa remained robust across all conditions. This suggests that a threshold developed under hot and humid conditions cannot adequately accommodate environmental variability. Statistical evaluation using linear regression and kernel density estimation (KDE) prediction regions further confirmed that when the threshold developed under cool and dry conditions was applied, the risk of false positives was negligible, while the false-negative risk, although still present, remained substantially lower than that associated with the threshold developed under hot and humid conditions.We conclude that while vacuum decay itself offers adequate resolution, threshold settings must account for environmental variability. A threshold developed under cool and dry conditions offers superior robustness and a wider safety margin. We therefore recommend adopting a risk-based strategy that favors threshold development under cooler and drier conditions to minimize false-negative risk and ensure long-term reliability.
PMID:
42919679
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 22
- Comments 0