Validation and Integrity Testing

Membrane systems used in bioprocessing applications need to be validated to demonstrate consistent purification and yield with minimal alteration in the properties of the product. Food and Drug Administration regulations provide specific guidelines for validation of sterile filters and virus removal membranes. Validation should always be performed at the same pH, ionic strength and chemical environment as used in the actual process to ensure equivalent physical and chemical characteristics of the product and impurities. Viral clearance studies are typically performed by spiking high titre infectious viruses (with different physical characteristics) into scaled-down production systems.

Integrity testing is critical for all sterile and viral filters to ensure that the system operates at the required level of performance. Integrity tests should be performed both prior to, and immediately after, the actual process wherever possible. Integrity tests performed prior to filtration must not affect the sterility of the connections downstream of the filter. The real test for the sterile filter would be to challenge with B. diminuta, but the filter could not be used after this test. Thus, a number of surrogate nondestructive integrity tests have been developed. The industry standards are forward flow, pressure decay and bubble point. Each of these tests is based on the displacement of a fluid from the pores by a second fluid (or gas), with the rate of displacement providing a measure of the membrane pore size characteristics. The gas or intrusion liquid expels the wetting liquid out of the pore when the feed pressure exceeds the capillary force within the pore. The bubble point is defined as the pressure at which the pore is first intruded by the gas. The bubble point for sterilizing grade filters can be correlated to the LRV of B. diminuta. Filters with water bubble points of 55 psi or greater typically yield the necessary LRV to be qualified as sterilizing-grade filters. In the forward flow test, one measures the total gas flow rate through the wetted membrane at a fixed pressure. High flow rates indicate the presence of pressure-driven flow through gas-intruded (large) pores. The pressure decay test is performed in a similar fashion, with the gas flow calculated from the rate of pressure decay. A variety of automated integrity test instruments have been developed by the different membrane manufacturers.

Bubble point tests with water-wetted membranes cannot be used to verify virus filter performance since the bubble points for these small pore size membranes would exceed the membrane pressure limits. Air diffusion and bubble point tests can be performed on these membranes using wetting fluids having lower surface tension (e.g. isopropyl alcohol). Liquid intrusion tests using two immiscible fluids (e.g. solutions of a sulfate salt and polyethyleneglycol) have been developed as integrity tests for virus filters and HPTFF membranes.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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