Pyrogenicity

Conventional
test method

Alternative Test Method

Last Reviewed
Name & Description Validation Status Regulatory Status Effect or Potential Effect on Animal Use
Rabbit Pyrogen Test (RPT)
(USP 151)
Human Whole Blood IL -1 In Vitro Pyrogen Test
Description and references
EU: Validated by ECVAM for the detection of pyrogenicity mediated by Gram-negative endotoxins (2006) 

US: Found suitable by ICCVAM for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT (2008)

No information Replacement
(when used to test for Gram-negative endotoxins)
May 2012
Human Whole Blood IL -6 in Vitro pyrogen test
Description and references
EU: Validated by ECVAM for the detection of pyrogenicity mediated by Gram-negative endotoxins (2006) 

US: Found suitable by ICCVAM for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT (2008)

No information Replacement
(when used to test for Gram-negative endotoxins)
May 2012
MM6 IL – 6 In Vitro Pyrogen Test
Description and references
EU: Validated by ECVAM for the detection of pyrogenicity mediated by Gram-negative endotoxins (2006) 

US: Found suitable by ICCVAM for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT (2008)

No information Replacement
(when used to test for Gram-negative endotoxins)
May 2012
PBMC IL - 6 In Vitro Pyrogen Test
Description and references
EU: Validated by ECVAM for the detection of pyrogenicity mediated by Gram-negative endotoxins (2006) 

US: Found suitable by ICCVAM for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT (2008)

No information Replacement
(when used to test for Gram-negative endotoxins)
May 2012
Human Cryopreserved Whole Blood IL-1 In Vitro Pyrogen Test
Description and references
EU: Validated by ECVAM for the detection of pyrogenicity mediated by Gram-negative endotoxins (2006) 

US: Found suitable by ICCVAM for use to detect Gram-negative endotoxin in human parenteral drugs on a case-by-case basis, subject to validation for each specific product to demonstrate equivalence to the RPT (2008)

No information Replacement
(when used to test for Gram-negative endotoxins)
May 2012
Limulus Amebocyte Lysate (LAL) Test a.k.a. Bacterial Endotoxin Test
Description and references
EU/US/Japan: To use test for regulatory purposes; an “in-house” validation program is required  EU: Accepted by EU and listed in the EDQM/European Pharmacopeia (5.0)

US: Accepted by the FDA and listed in the United States Pharmacopeia (USP 85)

Japan: Listed in Japanese Pharmacopeia XIV

Replacement
(Relative replacement: replacing more sentient animals with animals that current scientific peer advice and interpretation of scientific evidence indicate have a lower potential for pain perception)
May 2012
Limulus Amebocyte
Lysate (LAL) Test a.k.a. Bacterial Endotoxin Test
Recombinant Factor C (rFC) Bacterial Endotoxin Test
Description and references
US: Currently being compared to the Bacterial Endotoxin Test for inclusion in the USP No information Replacement May 2012

 

List of Abbreviations

Test Methods Categories

Toxicity
Dermal Tests
Vaccines