Dry-heat destruction of lipopolysaccharide: mathematical approach to process evaluation

Abstract

A mathematical model was developed to estimate the number of logarithmic cycles (LDec) of lipopolysaccharide concentration destroyed by a dry-heat sterilization process. The LDec values calculated from the mathematical model agreed well with those obtained from the destruction of lipopolysaccharide by a dry-heat treatment. A discussion of how the mathematical model may be used to evaluate a dry-heat sterilization cycle is presented. This mathematical model and the dryheat destruction curves indicated existence of a maximum LDec value at each temperature. The implications of this finding are discussed.

Endotoxin inactivation via steam‐heat treatment in dilute simethicone emulsions used in biopharmaceutical processes

“…Similarly, studies by Tsuji et al suggested that increasing exposure time to compensate for lower processing temperatures would not suffice to ensure comparable LPS inactivation. 20 Later work by Ludwig and Avis 16,17 interpreted LPS inactivation to be biphasic, wherein endotoxin reduction was assessed using two temperature-dependent linear fits. Between 170 C and 250 C, calculated D values have been reported from 0.15 min to 3.4 h 16,[18][19][20] (Figure 2).…”

“…20 Later work by Ludwig and Avis 16,17 interpreted LPS inactivation to be biphasic, wherein endotoxin reduction was assessed using two temperature-dependent linear fits. Between 170 C and 250 C, calculated D values have been reported from 0.15 min to 3.4 h 16,[18][19][20] (Figure 2). Z values vary depending on testing conditions with reported values of 15 C, 19 30.9 C, 18 46.8 C, 16,19 and 53.7 C 19 being observed.…”

“…The first relevant studies that sought to quantify the reduction of biologically active endotoxins using high temperatures were based on dry‐heat treatment strategies. Akers et al showed that a minimum processing temperature of roughly 170°C is required to reduce 10 ng of endotoxin by 2‐log, but subsequent work by Anderson and Kildsig presented that it is inappropriate to assume that this directly applies across the entire temperature range of a depyrogenation process.…”

“…Akers et al showed that a minimum processing temperature of roughly 170°C is required to reduce 10 ng of endotoxin by 2‐log, but subsequent work by Anderson and Kildsig presented that it is inappropriate to assume that this directly applies across the entire temperature range of a depyrogenation process. Similarly, studies by Tsuji et al suggested that increasing exposure time to compensate for lower processing temperatures would not suffice to ensure comparable LPS inactivation . Later work by Ludwig and Avis interpreted LPS inactivation to be biphasic, wherein endotoxin reduction was assessed using two temperature‐dependent linear fits.…”

“…Therefore, engineering controls should be built into a process to prevent contaminations from occurring. Reported endotoxin removal strategies cited in the literature include filtration techniques, chromatographic separations, two‐phase extraction, irradiation, dry‐heat applications, and hydrothermal processing . However, the specific method used to remove biologically active endotoxins from raw materials must be compatible with the end‐use of the raw material as well as subsequent processing requirements.…”