The in vivo rat muscle force model is a reliable and clinically relevant test of consistency among botulinum toxin preparations

Abstract

To ensure safety and predictable clinical efficacy, the biological activity of type A botulinum toxin (BoNT-A) preparations must remain consistent. Several methods have been employed to assess consistency but lack clinical applicability and/or are associated with animal welfare concerns. Here, we describe a novel in vivo rat muscle force model for evaluating the biological activity of formulated BoNT-A product (Dysport ®) prepared from bulk toxin batches manufactured at different facilities. Toxin activity was assessed by measuring muscle force generation over time in the triceps surae muscles in the rat hind leg. Animals received 0.1 ml gelatine phosphate buffer (negative vehicle control) or 0.1 or 1.0 LD 50 units of BoNT-A in phosphate buffer. Batch equivalence and consistency were confirmed by the lack of significant differences in muscle force generation and duration of effect between each test batch and the reference preparation tested in the same series of experiments. The reduction in muscle force generation was dose-related and reproducible for all active treatment groups. At appropriate dose levels, the rat muscle force model is a reliable tool for measuring biological activity in bulk toxin batches used to formulate clinical product and demonstrates the consistency of batches manufactured over many years.