Full Description
1.1 The microbial test method outlined in this test method applies to microbial ingress risk assessment of a single-use system (SUS) or its individual components that require integrity testing either by the assembly supplier or the end user of the assembly based on a potential risk of a breach to the product or manufacturing process.
1.2 The aim of microbial ingress testing of sterile SUSs used in biopharmaceutical manufacturing is two-fold:
1.2.1 Firstly, it is used to evaluate the ability of a SUS fluid path to remain sterile after a SUS has been challenged by microbial exposure. Microbial exposure is achieved either by directly placing a SUS into a container of microbial challenge solution, or by delivering an aerosolized microbial challenge onto a SUS that is placed inside a test chamber designed to generate and deliver the aerosol. The choice of the test challenge organism should be justified based on a risk assessment of the SUS and conditions of use.
1.2.2 Additionally, microbial ingress testing can be used to determine the maximum allowable leakage limit (MALL) that does not allow microbial ingress under specific test conditions. The defect size that can be detected by specific physical integrity testing methods (see Test Method
E3336) can be correlated to this MALL in order to claim microbial integrity. Test articles bearing calibrated defects over a range of dimensions, including up to a defect size expected to consistently allow microbial ingress as a positive control (defect-based positive control), may be tested to determine the MALL.
1.3 Both purposes for microbial ingress testing as described in
1.2.1 and
1.2.2 can either be conducted by liquid immersion or aerosol exposure. For the purpose described in
1.2.2, the type of exposure should be determined according to the SUS''s use-case conditions and a risk assessment.
1.4 The method used to create a breach, hole or defect in single-use film or in a SUS test article, as well as the analytical method used to physically characterize the defect size is outside of the scope of this test method. The sampling plan for a given test article should be justified with the rationale of sampling size to obtain a statistically meaningful effect (Practice
E3244). Determining the appropriate number of SUS test articles will depend on a risk assessment of the SUS and the conditions of its use and is also outside of this test method''s scope.
1.5 Units-The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.6 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.7 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. 
