Integrity testing is critical to ensuring a robust and reliable UF process operation. That is not only prudent from an economic perspective, but it also serves to conform with current good manufacturing practice (CGMP) guidelines. End users (manufacturers of drugs and vaccines) integrity test UF modules in a system to ensure proper installation and integrity of both membrane and module before committing expensive product streams to the system for processing. Membrane-retention tests confirm that manufactured membranes fall within their correct cut-off specifications before product release. Mixed dextran solution is a common marker used for UF membranes and modules ( 2). Membrane retention is tested using a protein solution or a solution of markers with known MWs. Prominent among such tests are those measuring membrane-retention profiles and modular integrity. Membrane manufacturers often use a number of tests to ensure membrane and module integrity during their manufacturing process. KEYWORDS: DIFFUSION TEST, MEMBRANE FILTRATION, CASSETTES, AUTOMATION, PRESSURE WHO SHOULD READ: ANALYTICAL AND DOWNSTREAM PROCESS DEVELOPMENT Flat-plate, spiral-wound, and hollow-fiber UF membranes can be incorporated into modular formats as well. Broadly speaking, a nonintegral membrane system can result from a damaged membrane or module, incomplete sealing of the membrane in its holder or assembly, and/or incorrect installation of the membrane module in that holder. An integral UF membrane system may be defined as one that retains a target product (or impurity) to a very high degree with minimal effect on process yield and recovery. An integral membrane system is required not only for achieving desired product yield and purification during process operation, but also for ensuring process consistency and adherence to good manufacturing practice (GMP) guidelines across multiple batches during a production campaign. One key factor that influences robust and successful operation of an ultrafiltration process is integrity of the membrane assembly. For a target product with a smaller MW than the impurities, separation is accomplished by allowing the product to pass through the membrane into the permeate side instead. A target product is retained by the membrane while lower-MW solutes or impurities pass through ( 1). The nominal MW limit of UF membranes ranges from 1,000 Da (1 kDa) to 1,000,000 Da (1,000 kDa). Ultrafiltration (UF) is a membrane-based separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove low–molecular-weight (LMW) impurities or exchange buffers.
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