Equine botulinum antitoxin is one of the most popular countermeasures for human botulism. The unitage of the antitoxin product is defined according to national minimum requirement or pharmacopoeia in each country by referring to national standard antitoxins for four types (A, B, E, and F). With the expected depletion of the national standard antitoxins, replacement national standard antitoxins are produced and standardized through collaboration of the National Control Laboratory and other participants, including manufacturer(s). Therefore, Japanese National Standard Botulinum Antitoxin Type A, Equine, was replaced according to the results of a collaborative study involving the National Institute of Infectious Diseases and KM Biologics Co., Ltd. The unitage of the replacement material was determined through mouse neutralization tests, which involved toxin-antitoxin mixture injection at pH 7.0. Potency value of 440 units/vial was obtained. However, the Japanese Minimum Requirement for Biological Products was revised, and the neutralization reactions were repeated at pH 6.0, for which considerably different potency value (656 units/vial) and survival profile of mice were obtained. In September 2021, the replacement material, Japanese National Standard Botulinum Antitoxin Type A, Equine, lot 2, was established with potency value of 656 Units/vial. The impact of pH-dependent change in potency on antitoxin quality control is discussed.

马肉毒杆菌抗毒素是人类肉毒杆菌中毒最流行的对策之一。抗毒素产品的单位是根据国家最低要求或各国药典，参照四类（A、B、E、F）抗毒素国家标准确定的。随着国家标准抗毒素的预期耗尽，国家控制实验室和包括制造商在内的其他参与者合作生产替代国家标准抗毒素并进行标准化。因此，根据国立感染症研究所和KM Biologics Co., Ltd.的合作研究结果，更换了日本国家标准A型肉毒杆菌抗毒素马。通过小鼠中和试验确定了替代材料的单位。其中涉及注射 pH 7.0 的毒素-抗毒素混合物。获得440单位/瓶的效力值。然而，日本对生物制品的最低要求进行了修订，并且在pH 6.0下重复中和反应，获得了显着不同的效价值（656单位/瓶）和小鼠的存活情况。2021 年 9 月，替代材料日本国家标准 A 型马用肉毒杆菌抗毒素，批次 2，效价为 656 单位/瓶。讨论了 pH 依赖性效力变化对抗毒素质量控制的影响。