I recently had an opportunity to speak with Dr. Tim Terrell, Senior Vice President of Drug Safety Evaluation at Allergan, about their exciting new FDA-approved, cell-based assay for the testing of BOTOX. Allergan released a press statement earlier this summer indicating that use of this cell-based test would lead to a 95% reduction in the number of animals used in the safety testing of BOTOX, demonstrating Allergan’s commitment to the 3 R’s - refinement, reduction, and replacement of animals used in product testing.
During my interview, Dr. Terrell indicated that Allergan’s dedication to the 3 R’s has been demonstrated over the years. Although the mouse LD50 test (Lethal Dose 50% test-an experiment performed to determine the amount of a chemical that kills 50% of the animals tested) had been used historically since the initial approval of BOTOX about 20 years ago, the company restructured the LD50 assay in 2006 to reduce the number of mice used. Scientists discovered that by implementing tighter controls in experiments, they could reduce the number of mice used by 50%.
But Allergan did not stop there- they recently made a change to BOTOX safety testing that will result in at least a 95% reduction in animal use by developing a cell-based assay to perform BOTOX potency tests. Allergan’s scientists faced many difficulties when developing and optimizing their new assay, and were presented with the additional challenge of getting approval from regulatory agencies to implement this new test. Regulatory agencies needed to be convinced of the accuracy, precision, and robustness of the cell-based assay, and needed significant data to demonstrate that results obtained from the cells were reliable. Fortunately, the in vitro assay proved to be an effective testing methodology to evaluate BOTOX potency -- and had the added bonus of substantially reducing the number of animals used in testing.
Allergan invested much time, effort, and money in the development of this assay. And while the company may never recoup the $65 million financial investment, they are extremely proud of their accomplishment. The in vitro assay has several advantages over the mouse LD50 test, including that it has the potential to be automated (operate automatically with help of computers and robotics). Allergan made this large investment in the development of the cell-based assay because “it is the right thing to do, scientifically, ethically, and otherwise,” said Dr. Terrell. He also indicated that the company is in the process of developing other in vitro assays, and feels that the knowledge scientists gained from developing the BOTOX in vitro assay will be invaluable when developing in vitro assays for other products.
NAVS is encouraged by the example set by Allergan, and we are hopeful that other companies will follow Allergan’s lead in developing cell-based assays to replace the use of animals currently used in product testing, and all other areas of research.
- Dr. Pam Osenskowski, Director of Science Programs