Three efficiency tests for single-use AEX chromatography devices have been developed and applied to six capsule formats of a new, salt tolerant, single-use AEX product. All the tests have been designed to be performed with simple equipment and common reagents. By performing each of the three tests on undamaged capsules and capsules intentionally damaged with small defects, in tandem with Phi-X174 challenges in a high-salt buffer, relationships between test results and viral clearance have been obtained. A pre-use pressure-based installation verification test is simply performed during equilibration of the device and effective at identifying gross bypass defects, for example, due to internal seal breakage. Passing outcomes of a post-use installation validation bubble point test are associated with ≥ 5 log reduction value (LRV) of viral clearance. A new, non-destructive, pre-use AEX capacity test involves challenging the device with chloride ions and is orthogonal to the other two tests in that it can detect chemical defects, as well as mechanical ones. Passing outcomes of this test correspond to > 2 LRV viral clearance and provide in situ assurance of the expected AEX dynamic capacity prior to use. Selection of a pair of pre-use and post-use tests can provide robust risk reduction with respect to viral clearance by single-use AEX devices in biopharmaceutical purifications.
Keywords: Anion exchange (AEX) chromatography; Downstream processing; Monoclonal antibodies (MAbs); Polishing chromatography; Single-use chromatography; Viral clearance.
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