Evaluation of the applicability of the bacterial endotoxin test to antibiotic products.
Fundamental conditions for applying the bacterial endotoxin test to antibiotic products were investigated so as not to affect the level of regulation by the rabbit pyrogen test. According to accuracy evaluation of test methods, the kinetic-turbidimetric and kinetic-colourimetric assays were shown to allow more accurate measurement and, therefore, more sensitive detection of interference to the bacterial endotoxin test than the gel-clot method. In total, 102 antibiotic products were evaluated on their interfering effect to show that the antibiotics could be categorized into three groups depending on intensity of the interference. Although the test was shown to be applicable even to the group showing the strongest interference, it was assumed to be crucial to use appropriate reagents and an accurate test method for avoiding approval of a pyrogenic product. Accordingly, lists of antibiotics are presented to provide limits of concentration for eliminating interference and endotoxin limits for approval to facilitate effective bacterial endotoxin tests.
Yamamoto
A
A
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, Japan.
Ochiai
M
M
Fujiwara
H
H
Asakawa
S
S
Ichinohe
K
K
Kataoka
M
M
Toyoizumi
H
H
Horiuchi
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000592:standards*; D001427:Bacterial Toxins / Q000032:analysis*; D001681:Biological Assay / Q000592:standards; D003124:Colorimetry / Q000379:methods; D004340:Drug Contamination / Q000517:prevention & control; D004731:Endotoxins / Q000032:analysis*; D005334:Fever; D008033:Limulus Test / Q000592:standards; D009391:Nephelometry and Turbidimetry / Q000379:methods; D011786:Quality Control; D011817:Rabbits; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004731:Endotoxins