Allergan gaining regulatory approval for cell-based assay for Botox potency

[Martin Stephens]

A year ago Horst Spielmann and I posted messages about Allergan's development of a cell-based assay for assessing the potency of Botox, a neurotoxin-based product used for cosmetic and medical purposes. This would replace the LD50 test in mice for this purpose.  At the time of its announcement, Allergan had gained regulatory approval for the new assay in the United States.  The challenge then was to gain regulatory approval in other markets.  A recent news item in the journal Altex by Silke Bitz provides an update on recent regulatory approvals of this assay in Europe--specifically Switzerland and "favorable opinions" in France and Ireland (http://www.altex.ch/en/index.html?id=17&ncat=1&nid=219).  The latter two countries have mutual recognition agreements with many other European countries, which bodes well for a broad-based international acceptance.

Does anyone have an update on the progress of other manufacturers of botulinum neurotoxin-based products in replacing the LD50 test?

Martin Stephens

[Sherry Ward]

I had difficulty locating these, so here are links to some previous postings on alternatives for BoNT testing:

http://forums.alttox.org/index.php?topic=683.0

http://forums.alttox.org/index.php?topic=685.0

[Horst Spielmann]

At a recent expert meeting the way forward for applying the new potency assay for BoNT-products of manufacturers other than Alergan was discussed. 
The mouse LD50 assay is currently the reference assay for potency and stability testing for all botulinum neurotoxin (BoNT)-products worldwide. A proprietary cell-based potency assay as an alternative for the LD50 assay has recently been validated and approved for Allergan’s BoNT-products Botox® and Vistabel® in the USA, Canada, Switzerland and EU. The approval of this alternative potency assay is limited to Allergan’s products and does not apply to BoNT- products of other companies.

BoNT-potency assays are product-specific and cannot be directly transferred to BoNT-products of other manufacturers without additional validation. An alternative assay to the mouse LD50 assay has to be suitable for the intended purpose (validated) and equivalent to the LD50 assay (cross validated). An alternative assay will also have to comprise relevant BoNT functions and has to be stability indicating.

Therefore scientists are strongly encouraged to focus on the development and validation of alternative BoNT potency assays that will reduce the number of animals used, or refine or replace the test procedure with the goal of promoting animal welfare in line e.g. with European legislation. At the same time manufacturers continue working towards development and validation of alternative BoNT potency assays.

Horst Spielmann