| dc.description.abstract | Botulinum neurotoxin (BoNT), more commonly known as Botox, is a biological
toxin produced by bacteria and is characterized by its paralytic effect on nerve
cells. BoNT is used for medical applications such as muscle spasms but is also
known for its use in the cosmetic treatment of facial wrinkles. Since BoNT is a
biological product, the characteristics and potency of the toxin can differ between
production batches. For this reason, potency tests need to be performed on each
batch of BoNT product to ensure its efficacy and safety. For these potency tests,
European guidelines require the use of a mouse LD50 test. In this mouse model,
a dilution series of BoNT product is injected into the abdomen of the mice, and the
concentration at which 50% of injected mice die is used to determine the potency
of this particular batch of BoNT. Over the course of the test, mice will become
unable to walk and eventually suffocate due to the failure of respiratory muscles.
However, during the test mice often die of starvation or dehydration because they
are unable to move to their food bowls and water taps because of muscle paralysis,
making the test unreliable. Both outcomes inflict great suffering on the mice. It
has been estimated that over 400,000 mice have died annually across the EU for
BoNT potency testing during manufacturing. In 2011 Allergan was the first major
BoNT manufacturer to develop and receive approval for a cell-based model for
BoNT potency testing. Unlike other available alternatives to the mouse model, this
cell-based model incorporates all crucial steps of the neurotoxin’s mechanism of
toxicity. Different BoNT products use different ingredients which can cause
problems if the assay is not adapted for these specific products, resulting in a
time-consuming validation process. This contributed to the other two major BoNT
manufacturers, Merz and Ipsen, taking years to validate a cell-based assay for
their own products. Even though all three major BoNT manufacturers in Europe
now use a cell-based assay to replace some amount of their animal testing, the
number of mice used for BoNT potency testing had actually increased in the years
leading up to 2019. This is likely the result of new manufacturers bringing their
BoNT products to the EU market, EU regulatory guidelines stating that some
quality control tests still need to be performed using the mouse model, and the
total amount of produced BoNT increasing to keep up with rising consumer
demand. Animal rights organizations are disappointed with this development,
especially considering BoNT is commonly used for cosmetic treatments. Even
though animal testing for cosmetics has been banned in the EU since 2013, BoNT
products avoid this ban due to having genuine medical applications and are thus
classified as medicines. However, in both the Netherlands and the rest of the EU,
off-label prescription of BoNT for vanity reasons is common. Even though LD50
testing is prohibited in the Netherlands, BoNT products which were tested on mice
are still marketed and sold there for cosmetic purposes. Since 2019, the EU has
done little to help finalize the replacement of LD50 testing for BoNT. EU regulatory
guidelines need to be updated to fully remove LD50 testing as part of the quality
control process and until all BoNT products are ‘cruelty-free’, off-label prescription
of these products for vanity reasons should be prohibited. | |
