PT  - JOURNAL ARTICLE
AU  - Andrea Buchacher
AU  - Dagmar Krause
AU  - Gerda Wiry
AU  - Josef Weinberger
TI  - Elevated Endotoxin Levels in Human Intravenous Immunoglobulin Concentrates Caused by (1→3)-β-D-Glucans
DP  - 2010 Nov 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 536--544
VI  - 64
IP  - 6
4099  - http://journal.pda.org/content/64/6/536.short
4100  - http://journal.pda.org/content/64/6/536.full
SO  - PDA J Pharm Sci Technol2010 Nov 01; 64
AB  - Endotoxins have been measured routinely in the final product and during the production process to produce non-pyrogenic parenterals. Limulus-amoebocyte-lysate-reactive material was found in in-process samples and final product of one of Octapharma's intravenous immunoglobulin (IVIG) preparations. Limulus-amoebocyte-lysate (LAL) is activated by bacterial endotoxins and by (1→3)-β-D-glucans. The contribution of both compounds on the LAL-related signal was determined by three different approaches: (1) using a test specific for (1→3)-β-D-glucans, (2) by addition of β-glucan blocker, and (3) by the use of a recombinant endotoxin assay. It was shown that none of our IVIG concentrates contained elevated endotoxin contents but that the higher LAL reaction could be ascribed to (1→3)-β-D-glucans extracted from cellulose filter pads. The use of an endotoxin test kit highly sensitive for (1→3)-β-D-glucans might lead to false-positive results. (1→3)-β-D-glucans spike solutions did not evoke an increase of temperature in rabbits, suggesting that a pyrogenic reaction is not expected in patients. LAY ABSTRACT: Endotoxins have been measured routinely in the final product and during the production process to produce non-pyrogenic parenterals. Limulus-amoebocyte-lysate-reactive material was found in in-process samples and final product of one of Octapharma's intravenous immunoglobulin (IVIG) preparations. Limulus-amoebocyte-lysate (LAL) is activated by bacterial endotoxins and by (1→3)-β-D-glucans. The contribution of both compounds on the LAL-related signal was determined by three different approaches: (1) using a test specific for (1→3)-β-D-glucans, (2) by addition of β-glucan blocker, and (3) by the use of a recombinant endotoxin assay. It has been shown that none of our IVIG concentrates contained elevated endotoxin contents but that the higher LAL reaction could be ascribed to (1→3)-β-D-glucans extracted from cellulose filter pads. The use of an endotoxin test kit highly sensitive for (1→3)-β-D-glucans might lead to false-positive results. (1→3)-β-D-glucans spike solutions did not evoke an increase of temperature in rabbits suggesting that a pyrogenic reaction is not expected in patients.