Comparison of bacterial and endotoxin retention by charge-modified sterilizing grade filters during intermittent...

There has been growing concern in recent years about control of bacterial bioburden and endotoxin in pharmaceutical water systems by both the pharmaceutical manufacturers and the Food and Drug Administration (FDA). This concern exists not only for Water for Injection (WFI) systems, but for any water system used in the manufacture of a product which could be affected by the microbial bioburden. In hot WFI systems, bioburden control is assured by keeping the water in the recirculating loops at 80 degrees C. At points of use in these systems, the temperature fluctuates and can be below sanitization temperature for extended periods. On the other hand, in cold water systems [WFI and deionized (DI)], both bioburden and endotoxin control are more difficult. This study shows that sterilizing grade, positively-charged filters can provide absolute bioburden control. In addition, these filters effectively retain high levels of both purified and cell-associated endotoxins over a five month period under severe intermittent system use conditions in a model high-purity water system. This study suggests a solution to the concerns over long-term use of bacterially retentive filters in properly maintained high-purity water systems.