Martex Research and Development was an up-and-coming force in the pharmaceutical industry betting on the success of Baluride, its first injectable monoclonal antibody. As required by federal regulation, the company tested each lot of final containers of Baluride for pyrogenic (fever-causing) substances by intravenous injection of Baluride into rabbits. For the Martex IACUC, this was almost a routine procedure considering the number of times the Committee had approved this test. There were no reported problems and after its initial approval, the IACUC did not revisit the specific activities under that protocol apart from the annual USDA-mandated protocol review.
About two years after the IACUC approved the rabbit pyrogenicity test for Baluride, Martex (following federal specifications) validated the Limulus Amebocyte Lysate test (LAL) for Baluride as an alternative to the use of rabbits. The company subsequently had its product license properly amended to use either the LAL or rabbit test. Martex and its legal team decided to continue with limited rabbit testing for a short time longer, concurrent with the use of the LAL, until the company could be fully assured that there would be no regulatory, technical, or legal problems from switching mid-production to the LAL.
None of these activities were of particular concern to the Martex IACUC, which simply assumed that upper management's decision was appropriate and binding. However, as could be expected, the word spread about the Martex IACUC's approval of the LAL for Baluride. When that happened, various animal rights groups in the area demanded that Martex immediately abandon all rabbit pyrogenicity testing for Baluride. Martex was in a quandary as to the best way to react. While this was being debated within the company, the animal rights groups contacted the USDA, demanding that the USDA enforce §2.31(d)(1)(ii) of the Animal Welfare Act regulations (AWARs), which they said required Martex to use the LAL because it was an available and now validated alternative to the use of rabbits and would replace a potentially painful or distressful procedure.
If you were a member of the Martex IACUC, would you agree that the LAL test should be immediately substituted for all Baluride rabbit pyrogenicity testing? Does the IACUC or the USDA have the authority to make such a demand on the company, apart from the normal protocol review process?
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Silverman, J. Validated alternatives: is immediate implementation required?. Lab Anim 36, 13 (2007). https://doi.org/10.1038/laban0507-13a
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DOI: https://doi.org/10.1038/laban0507-13a
