ABSTRACT

FILTRATIVE SEPARATION Sterile filtration is widely used in the biopharmaceutical industry to remove contaminants, especially microorganisms from liquids and gases. Microorganism removal is required either to achieve a sterile filtrate or to reduce bioburden levels, which in turn decreases endotoxin threats. Sterilizing grade membrane filters are defined by the FDA Guideline on Sterile Drug Products Produced by Aseptic Processing, 2004 by being able to retain more than 107

Brevundimonas diminuta (formerly Pseudomonas diminuta) organisms per cm2 of filtration area at a differential pressure of 29 psi (2 bar). The retention efficiency has to be validated, using the actual drug product and the process parameters, because of the possibility of an effect to the filters compatibility and stability and/or the microorganism size and survival rate. Performing product bacteria challenge tests became a regulatory demand in 1995 and is now a part of standard filter validation (1). Prior to performing challenge tests, the appropriate challenge methodology has to be evaluated via viability tests. These tests determine the mortality rate of the challenge organisms due to product or process parameters. PDA Technical Report No. 26, 2008, describes the individual parameters, the possible effects, and mechanisms to be used to perform challenge tests. Additionally, the report discusses filtration modes, sterilization, and integrity testing. Multiple parts of this document have also been adopted by ISO (2) and the FDA Aseptic Guideline (3).