The U.S. Food and Drug Administration (FDA) and other worldwide health regulatory agencies currently require all pharmaceutical manufacturers to protect patients and consumers by establishing product quality, safety and effectiveness through approved and validated testing methods, which include animal testing in some instances.
Allergan shares the pharmaceutical industry's goal of reducing or eliminating animal testing wherever possible and is committed to the "3Rs" principles of refinement, reduction and eventual replacement of laboratory animals in product testing.
Allergan is pleased, that after more than a decade of research and development and an approximately $65 million investment, we have minimized to the greatest degree possible the need for animal-based assays in the manufacture of BOTOX® and BOTOX® Cosmetic. In June 2011, the United States Food and Drug Administration (FDA) approved the first fully in vitro, cell-based assay for use in the stability and potency testing required for the sale of BOTOX® (onabotulinumtoxinA) and BOTOX® Cosmetic in the United States. Allergan estimates that use of the new assay will reduce the use of animal-based assay testing for BOTOX® and BOTOX®Cosmetic by up to 95 percent or more over the next three years, as other regulatory agencies around the world approve this new assay. The new assay is the first to be developed and approved for any botulinum neurotoxin currently available worldwide, and is specifically applicable to Allergan’s botulinum toxin type A product.
We are proud to have achieved this major scientific milestone in the development of a safe and effective alternative test capable of eliminating the need for an animal-based assay for BOTOX® and BOTOX® Cosmetic. Following the FDA approval, we will work hard to secure approval of the new assay to replace the current animal testing requirements for the release and stability testing of BOTOX® and BOTOX® Cosmetic in countries in which we market and distribute the product.
About the BOTOX® Cell-Based Potency Assay (CBPA)
Over the years a number of attempts have been made to find strategies to replace the animal-based LD50 assay for testing of botulinum neurotoxins but have fallen short for a variety of reasons. The mouse LD50 potency assay is required by the FDA, the Medicines and Healthcare products Regulatory Agency (MHRA) in Europe and regulatory agencies around the world for testing final product for release to assure its safety and efficacy. Limitations associated with the current mouse LD50 assay, which has been the standard for potency and stability testing of BOTOX® and BOTOX®Cosmetic and other botulinum neurotoxin type A products, include the necessary involvement of animals due to the current structure of the assay, the complexity of the procedures involved, lack of specificity, as well as variability between assays and laboratories.
Botulinum neurotoxin is one of the most potent naturally occurring substances and has a complex multi-stage mechanism of action. Purified botulinum neurotoxin type A is the active ingredient in BOTOX® and blocks the release of neurotransmitters from nerves, resulting in a localized and temporary reduction in the overacting muscle or gland. The amount of neurotoxin in BOTOX® is extremely small; in fact, less than one gram per year is required to supply the entire world.
A suitable replacement potency assay to the LD50 assay must therefore be sensitive enough to measure the complex mode of action of extremely small amount of the neurotoxin used in BOTOX® in the cellular level. Established performance criteria against which the new cell-based potency assay needed to be validated included the ability to assess all primary modes of action of the neurotoxin. In addition, the new assay format had to be suitable for use in an intensely quality-controlled environment and at the high capacity needed to support commercial production.
The new cell-based potency assay for BOTOX® and BOTOX® Cosmetic is specific to Allergan’s formulation of botulinum neurotoxin type A. Allergan is discussing how to license the technology to other parties that share its commitment to implementing non-animal alternatives to animal-based assays in the manufacture of their medical products.