Significance and Use
4.1 The test methods outlined in this standard allow for suppliers and end users of SUSs in (bio)pharmaceutical manufacturing processes to detect a leak and/or confirm the barrier properties of empty, clean, and dry SUSs. Performing integrity testing can be a significant contribution to the overall integrity assurance of SUSs.
4.2 The two types of physical test methods outlined in this standard are:
4.2.1 Section 5, Pressure-Based Test Methods.
4.2.2 Section 6, Tracer Gas-Based Test Methods.
Note 3: Other test methods are currently being adapted for robust, reliable, and reproducible testing SUS, for example, Vacuum Decay Test Method as described in Test Method F2338.
4.3 Pressure-based test methods are generally less sensitive compared to tracer gas-based test methods but have a lower complexity and cost. To assist in selecting a method that will fit an application, refer to Table 1 in Practice E3244 for a more detailed comparison of the two methods.
4.4 Both types of test methods can be used to detect leaks of any sizes in a SUS (referred to as leak testing) or confirm the barrier properties of the SUS (referred to as integrity testing).
4.5 To ensure that integrity testing performed on SUSs is effective and accurate, the properties of the SUS (pressure capabilities, volume, material properties, etc.) must be considered. Also, a validation should be performed on the chosen test method as further described in 5.11 and 6.11.
4.6 Practice E3244 should be referenced to determine the maximum allowable leakage limit for a SUS, along with the routine testing requirements that are suitable for each application.
4.7 The purpose of the described test methods is not to stress the SUS until a potential defect occurs. The testing parameters, mainly test pressure, are independent from the use-case conditions. The robustness of the SUS under use-case conditions should be proven during product qualification.
4.8 This standard test method describes the test method principles, the apparatus designs, and method validations. For more detailed visualization of test setups and tested SUS designs, refer to Practice E3244 and more illustrative technical guides (5).
Scope
1.1 The test methods described in this standard are applicable for single-use manufacturing equipment, further called Single-use Systems (SUSs), used for (bio)pharmaceutical products.
1.2 The test methods described in this standard are not intended to be used on single-use technology for primary containers, combination products (products composed of any combination of a drug, device, or biological product), or devices. Appropriate procedures related to these products are discussed in documents covering the integrity assurance for primary containers (1)2 or medical products (2-4).
1.3 The test methods and their validation are described to only cover testing of empty and dry SUSs. Residual liquid in the SUS can impact the test reliability and reproducibility.
1.4 The test methods are intended to be used to confirm the barrier properties of the test article, further called integrity testing, or test the SUS for leaks of certain sizes, further called leak testing.
Note 1: To verify that an integrity test can confirm the intended barrier properties of the SUS, its detection limit must be equal or better than the respective maximum allowable leakage limit.
1.5 The physical test methods covered by this standard are:
1.5.1 Pressure-based test methods.
1.5.2 Tracer gas-based test methods.
1.6 The physical test methods described are in general non-destructive and allow further use of the SUS.
Note 2: Some variations can be used in a destructive way, for example, to perform root cause analysis of the leak.
1.7 The standard describes the test apparatuses, operation procedures, environment requirements, and discusses specific challenges with testing SUSs, as well as how to perform robust validation of the test method.
1.8 This standard does not include methods to determine the maximum allowable leakage limit for maintaining the barrier properties of the SUS. For that, refer to Practice E3244 and Test Method E3251.
1.9 This standard does not describe how to select the appropriate test method. For that, refer to Practice E3244.
1.10 Furthermore, it does not discuss whether an integrity test should be conducted, at what frequency and where in the life cycle of a SUS. For that refer to Practice E3244.
1.11 Filter membrane integrity testing that additionally tests the integrity of the SUS is excluded from the scope. Certain components of the SUS may require additional testing.
1.12 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.
1.13 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.
