Detection of systemic hypersensitivity to drugs using standard guinea pig assays.
The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.
Weaver
James L
JL
Office of Testing and Research, Division of Applied Pharmacology Research, Center for Drug Evaluation and Research (CDER), MOD-1, 8301 Muirkirk Rd, Laurel, MD 20708, USA. weaver@cder.fda.gov
Staten
David
D
Swann
Joslyn
J
Armstrong
George
G
Bates
Melissa
M
Hastings
Kenneth L
KL
D016907:Adverse Drug Reaction Reporting Systems; D000818:Animals; D016208:Databases, Factual; D017277:Drug Approval; D004342:Drug Hypersensitivity; D006168:Guinea Pigs; D006801:Humans; D011358:Product Surveillance, Postmarketing; D014481:United States; D014486:United States Food and Drug Administration