title: Elevated Endotoxin Levels in Human Intravenous Immunoglobulin Concentrates Caused by (1->3)-{beta}-D-Glucans.
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 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.
  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.
authors.affiliation: Quality Control Department, Octapharma Pharmazeutika ProduktionsGmbH, Oberlaaerstrasse 235, 1100 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Buchacher
authors.forename: Dagmar
authors.initials: D
authors.lastname: Krause
authors.forename: Gerda
authors.initials: G
authors.lastname: Wiry
authors.forename: Josef
authors.initials: J
authors.lastname: Weinberger
mesh_terms: D000818:Animals; D002482:Cellulose; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D005936:Glucans; D019382:Human Growth Hormone; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007262:Infusions, Intravenous; D008033:Limulus Test; D047071:beta-Glucans
chemical_list: D004731:Endotoxins; D005936:Glucans; D016756:Immunoglobulins, Intravenous; D047071:beta-Glucans; D019382:Human Growth Hormone; D002482:Cellulose