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Standard Practice for Validating End-User Sterilizing Filtration of Pharmaceutical, Biopharmaceutical, and Biological Products
1.1Â Process validation of sterilizing filtration is required by industry standards and regulatory agencies to ensure that process fluid contact with the filter under actual worst-case process-use conditions (that is, time, flux, temperature, and pressure differential) do not adversely affect the composition of the filtered material, the retentivity and integrity of the filter, and the filtration process is capable of producing a sterile filtrate.
1.2 In this practice, guidance is provided for bacterial challenge validation of sterilizing-grade filters demonstrating the membrane filter’s ability to retain the challenge organism completely, typically Brevundimonas diminuta (ATCC 19146) or another suitable bacterium at a minimum challenge level of 1 × 107 CFU/cm2 of effective filtration area (EFA), under process-specific conditions using the actual process fluid or a surrogate fluid when necessary with the specified filter membrane material and composition.
1.3 Units—The values stated in SI units are to be regarded as the standard. No other units of measurement are included in this standard.
1.4Â 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.
1.5Â 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.
4.1Â This practice may be used to evaluate the microbial retentivity of any membrane filter used for liquid sterilization where validation is required in the manufacturing of pharmaceutical, biopharmaceutical, and biological products or their intermediates (where applicable). These processes may include, but are not limited to, cell culture media, buffers, intermediate holds in aseptic process, bulk, and sterile filtering.
4.2Â In this practice, a framework for the development of an appropriate bacterial retention testing strategy based on applicable scientific and regulatory considerations is described. Alternative approaches may also be acceptable provided they are supported by sound scientific rational and risk assessments.
4.3Â This practice was developed with certain assumptions in mind such as completion of appropriate investigative or testing activities, or both, for filter selection including chemical compatibility, active ingredient and preservative binding, and particle shedding before pursuing process-specific bacterial retention testing. Test methods and guidance for filter selection, therefore, are not included in this practice. Additionally, process bioburden should be sufficiently studied to support the rationale for determining the most appropriate challenge organism for use in bacterial retention testing.
4.4Â This practice conforms to sterile filtration recommendations established by PDA TR 26, Test Method F838, FDA Guidance for Industry, EU GMP Annex 1, and ISO 13408-2.
| SDO | ASTM: ASTM International |
| Document Number | E3469 |
| Publication Date | April 1, 2026 |
| Language | en - English |
| Page Count | 14 |
| Revision Level | 26 |
| Supercedes | |
| Committee | E55.13 |