RelabotulinumtoxinA, a Ready-to-Use Formulation Neuromodulator Manufactured with PEARL™ Technology to Maintain High Biological and Specific Activity

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary <i>C. botulinum</i> type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸-2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs.