Risk of false conformity decisions in LAL gel-clot test due to false-negative results

Abstract

Endotoxins are impurities capable of causing multiple deleterious effects to health. Therefore, the results of Limulus horseshoe crab amebocyte lysate (LAL) coagulation test in injectable drugs should be reliable. However, the reliability of qualitative results is still a challenge for analytical chemists and microbiologists. Thus, the objective of this work is to estimate the risk of false compliance/non-compliance decisions in LAL test based on the probability of true-negative and false-negative results through likelihood ratio value (LHR). For this, 11 injectable drugs were analyzed in two dilution schemes. A total of 1560 tests were performed using 41 different lots of LAL. The results from the confirmation of lysate sensitivity were used to obtain a logistic regression model, thus enabling to estimate the probability of negative results and consequently the LHR of the drug tests. LHR values were found to be between about 102 (114) and 105 (117,206), which corresponds to evidence of moderately strong to extremely strong negative results. Higher LHR values were obtained using lower dilution schemes. The use of logistic regression and calculation of LHR values can be useful to assess the reliability of qualitative results obtained by other chemical or microbiological methods.