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(1) Background: At present, the only potency assay approved in China for the in-country testing of botulinum toxin type A for injection products is the mouse bioassay (MBA). The Chinese market for neurotoxin products is rapidly expanding, but MBAs are subject to high variability due to individual variations in mice, as well as variations in injection sites, in addition to the limited number of batches tested for one MBA. Compared with the mLD₅₀ method, the cell-based potency assay (CBPA) developed for the potency testing of onabotulinumtoxinA (BOTOX) by AbbVie not only does not use any experimental animals but also allows for significant time and cost savings. Due to the significant benefits conferred by the replacement of the mLD₅₀ assay with CBPA in China, the CBPA method has been transferred, validated, and cross-validated to demonstrate the equivalence of the two potency methods. (2) Methods: The differentiated SiMa cells were treated with both BOTOX samples and the reference standard, and the cleaved SNAP25₁₉₇ in the cell lysates was quantified using Chemi-ECL ELISA. A 4-PL model was used for the data fit and sample relative potency calculation. The method accuracy, linearity, repeatability, and intermediate precision were determined within the range of 50% to 200% of the labeled claim. A statistical equivalence of the two potency methods (CBPA and mLD₅₀) was initially demonstrated by comparing the AbbVie CBPA data with NIFDC mLD₅₀ data on a total of 167 commercial BOTOX lots (85 50U lots and 82 100U lots). In addition, six lots of onabotulinumtoxinA (three 50U and three 100U) were re-tested as cross-validation by these two methods for equivalence. (3) Results: The overall assay’s accuracy and intermediate precision were determined as 104% and 9.2%, and the slope, R-square, and Y-intercept for linearity were determined as 1.071, 0.998, and 0.036, respectively. The repeatability was determined as 6.9%. The range with the acceptable criteria of accuracy, linearity, and precision was demonstrated as 50% to 200% of the labeled claim. The 95% equivalence statistic test using margins [80%, 125%] indicates that CBPA and mLD₅₀ methods are equivalent for both BOTOX strengths (i.e., 50U and 100U). The relative potency data from cross-validation were within the range of ≥80% to ≤120%. (4) Conclusions: The CBPA meets all acceptance criteria and is equivalent to mLD₅₀. The replacement of mLD₅₀ with CBPA is well justified in terms of ensuring safety and efficacy, as well as for animal benefits. Full article

This work provides a comprehensive analysis of the maximum chromatic axial split of two-element hyperchromats, with the distance between the two lenses being a key variable. Purely refractive and diffractive systems are considered, as well as hybrid layouts combining refractive and diffractive elements. In order to achieve extreme chromatic axial splitting and accordingly a minimum equivalent Abbe number for lens combinations, a three-step procedure was used. In the first paraxial step, purely optical quantities such as focal lengths of the lenses, inter-lens distances and dispersion properties of the lenses were investigated. In the second step, which also takes place in the paraxial domain, additional geometric boundary conditions such as the radii, diameters and thicknesses of the lenses are taken into account. The results of this step serve as an input for the final optimization using optical design software, which derives practical solutions for minimum equivalent Abbe numbers with diffraction-limited image quality. As a significant result, the comparison with directly cemented lens doublets shows that the introduction of a distance between the elements allows for a much stronger chromatic decomposition for refractive, diffractive and also hybrid combinations. Quantitatively, the minimum equivalent Abbe number for refractive systems is reduced from 2.5 (without spacing) to 1.79 (with spacing). For hybrid combinations, a corresponding reduction from 0.4 to 0.29 is achieved. Full article