RT Journal Article
SR Electronic
T1 A Risk Based Approach for Pre-Use/Post-Sterilization Integrity Test Simulation During Bacterial Retention Testing as Part of the Process Specific Filter Validation of Sterilizing Grade Filters
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2024.012990
DO 10.5731/pdajpst.2024.012990
A1 Salamatian, Mariam
A1 Gross, Yvonne
A1 Stering, Magnus
A1 Vinh, Thao Le
A1 Bindels, Ashira
YR 2025
UL http://journal.pda.org/content/early/2025/05/19/pdajpst.2024.012990.abstract
AB Pre-Use Post Sterilization Integrity Testing is implemented in sterile filtration applications by drug manufacturers using a risk-based approach with consideration of the stipulation in Eudralex volume 4, Annex 1, of the European Union Good Manufacturing Practice for Sterile Products′ which states that ″The integrity of the sterilizing filter should be verified before use″ (1). Within the bacterial retention test design, performed as part of the process-specific sterile filter validation, it is important to simulate the filtration process under evaluation as closely as possible. Worst-case conditions experienced by the process filter during routine use that may impact the process filters′ ability to produce a sterile effluent should be accounted for in the study. As performing pre-use post sterilization integrity testing introduces additional mechanical stress on the process filter and a new potential route for the introduction of bioburden into the process fluid flow path related to the filter wetting procedure, a risk-based bacterial retention test design incorporating a pre-use post sterilization integrity testing simulation phase, should be considered after a thorough evaluation of the process specific conditions. The risk assessment should include evaluation of process pre-use post sterilization integrity testing conditions including but not limited to the integrity test method and specifications, the wetting fluid type, the maximum allowable number of pre-use post sterilization integrity test repetitions as well as the permitted bioburden level of the pre-use post sterilization integrity testing wetting fluid. The outcome of the assessment provides a basis for the process specific bacterial retention test design. In the following we present our perspective on the topic as well as detailed insight into various aspects of pre-use post sterilization integrity testing simulation test design for consideration.