Botulinum neurotoxin: Tracking the transition from lethal dose to in vitro models

Area of Science:

• Pharmacology
• Toxicology
• Biotechnology

Background:

• Botulinum neurotoxin (BoNT) is essential for medical and aesthetic uses.
• Current BoNT potency testing relies on the ethically problematic Mouse Lethality Bioassay (MLB).
• New Approach Methodologies (NAMs), including cell-based assays (CBAs), offer non-animal alternatives.

Purpose of the Study:

• To update on the transition to non-animal NAMs for BoNT potency testing in Europe.
• To describe accepted MLB alternatives and BoNT product distribution in the EU/UK.
• To estimate annual mouse usage for BoNT testing by analyzing Non-Technical Summaries (NTSs).

Main Methods:

• Analysis of publicly available Non-Technical Summaries (NTSs) from UK, Germany, and Ireland.
• Review of regulatory documents and scientific literature on BoNT testing alternatives.
• Synthesis of findings to identify barriers to NAM implementation.

Main Results:

• The MLB has likely ceased in Germany but continues in the UK and Ireland.
• MLB use persists even with developed CBAs due to regulatory and validation needs.
• Estimating precise mouse numbers for BoNT testing proved difficult, highlighting transparency issues.

Conclusions:

• Transitioning away from MLB for BoNT potency testing faces systemic barriers.
• Cell-based assays (CBAs) are viable alternatives but require regulatory acceptance and validation.
• Increased transparency in animal use data is crucial for ethical and scientific advancement in BoNT testing.