TY - JOUR T1 - Validating Container Closure Integrity with Statistically Based Tests JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2020.012622 SP - pdajpst.2020.012622 AU - Dan Coleman AU - Tony Pourmohamad AU - Yenny Webb Vargas AU - Maury Mossman Y1 - 2021/01/01 UR - http://journal.pda.org/content/early/2021/05/14/pdajpst.2020.012622.abstract N2 - Two statistically based testing procedures, a zero-failure test and a one-failure test, are proposed for demonstrating that a vial capping process has an acceptably low rate of failed seals, i.e., non-integral container closures, or leaky vials. These tests are developed for use with the standard helium-leak test method that measures the amount of escaped helium from a capped vial. The amount of escaped helium is a continuous measurement and a vial is said to be leaky if the measurement exceeds a threshold and not leaky if it does not. Not leaky measurements are often less than the lower limit of validation, i.e., left-censored. By using the continuous measurements that describe the extent of leaking instead of the binary measurements, leaky or not leaky, the proposed tests are able to reach similar conclusions as tests using binary measurements but with much smaller sample sizes. The proposed tests can handle any number of measurements less than the lower limit of validation. ER -