Log Removal Values Research Articles

Removal of prion challenge from an immune globulin preparation by use of a size-exclusion filter.

A size-exclusion filter (Viresolve 180, Millipore Corp.) was tested for its ability to remove transmissible spongiform encephalopathies prion protein from an immune globulin preparation during ultrafiltration. Hamster-adapted 263K scrapie brain homogenate (SBH) was spiked into Rh0(D) immune globulin (human) at 1 in 300 and 1 in 1000 dilutions. Before spiking, the SBH was treated with detergent, sonicated, and filtered through serial 0.45-, 0.22-, and 0.1-microm filters to present a rigorous filter challenge. Process variables were monitored throughout the ultrafiltration to ensure that the spiked material did not compromise the membrane flux. Removal of scrapie prion protein (PrP(Sc)) material was determined by use of a sensitive Western blot assay. The turbid SBH became completely translucent after sonication and passage through the 0.45-, 0.22-, and 0.1-microm filters. The filtration of the immune globulin containing PrP(Sc) material was more difficult to perform than was filtration of immune globulin spiked with the normal cellular isoform. Even during tangential flow filtration, the fibril material prevented the PrP(Sc)-spiked immune globulin from passing as readily through the filter. Western blot results indicated a removal of greater than or equal to 2.5 log PrP(Sc), while remaining within the normal filtration limits. The composition, physical condition, and the amount of SBH introduced have significant effects on the filtration of the immune globulin and the log removal values obtained. By use of a detergent-treated, sonicated, and filtered preparation of SBH, it was demonstrated that the Viresolve 180 effectively removes PrP(Sc) from the immune globulin.

Removal of sulphite-reducing clostridia spores by full-scale water treatment processes as a surrogate for protozoan (oo)cysts removal

At eight full-scale water treatment plants in the Netherlands the removal of spores of sulphite-reducing clostridia (SSRC) was determined. By sampling and processing large volumes of water (1 up to 500 litres) SSRC were detected after each stage of the treatment. This enabled the assessment of the removal efficiency of the full-scale unit processes for persistent micro-organisms. A comparison with literature data on the removal of Cryptosporidium and Giardia by the same type of processes revealed that SSRC can be considered as a potential surrogate. The average Decimal Elimination Capacity (DEC) of the overall treatment plants ranged from 1.3–4.3 log. The observed actual log removal of SSRC by the unit processes and the overall treatment at one of the studied locations showed that the level of variation in removal efficiency was approximately 2 log. Moreover, from the actual log removal values it was observed that a low SSRC removal by one unit process is partly compensated by a higher removal by subsequent unit processes at this location. SSRC can be used for identification of the process conditions that cause variation in micro-organism removal which may lead to process optimization. Further research is necessary to determine the optimal use of SSRC in water quality monitoring for the production of microbiologically safe drinking water.

Evaluating particle counters

Comparisons of particle counts made by counters and counts made by microscopic processes suggest counters accurately indicate removal efficiency.Particle counting methods for use in a water treatment facility were analyzed to compare counts made by a particle counter with a forward‐angle light scatter (FALS) sensor with counts made with a scanning electron microscope and by microscopic particulate analysis. A separate study compared an FALS sensor with a light obscuration sensor when challenged with latex spheres and cultured microorganisms and when performing continuous in‐line counts of the facility's filter effluent. Log removal values were comparable among the particle counting methods and did not vary significantly across various size ranges of an FALS sensor. Microorganisms were undersized by both sensor types compared with sizes determined with an optical microscope. These results suggest counters accurately indicate facility particle removal efficiency. However, counts made by a particle counter within a specific size range should be interpreted after characterizing the nature of the particles in the source

A Validatible Porosimetric Technique for Verifying the Integrity of Virus-Retentive Membranes

Abstract.The verification of membrane integrity for filtration processes specifically designed for the removal of adventitious virus from biotherapeutics is of the utmost importance to both biomanu-facturers and regulatory agencies. Although conventional bubble-point and air-diffusion tests are widely accepted for integrity testing of bacteria-retentive membranes, these tests have severe limitations in their ability to assess the integrity of virus-retentive membranes. A novel membrane integrity test based upon liquid—liquid porosimetric principles (CorrTest™) has been specifically designed to correlate and predict the virus retention capabilities of Viresolve™ virus removing membranes. To optimize test sensitivity for both Viresolve/70™ and Viresolve/180™ membrane types, two distinct porosimetric correlations at different transmembrane pressures have been developed. Based upon an 80% prediction interval, an integrity test performed at either test pressure can reliably predict the ability of Viresolve™ membranes to remove the bacteriophage φX174 to within 0·4 log removal value (LRV) units. To maintain test sensitivity and provide greater flexibility for conducting the liquid—liquid intrusion integrity test, appropriate pressure- and temperature-correction equations have been established. The two immiscible fluids employed in the developed technology are easily flushed from the membrane structure and are generally regarded as acceptable, non-toxic reagents for pharmaceutical applications. Consequently, the CorrTest™ integrity test can reliably and non-destructively measure both pre- and post-use membrane integrity to verify virus removal performance with the Viresolve™ module.