Movement Disorders Section, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany.
Toxicon. 2020 Feb;175:64-68. doi: 10.1016/j.toxicon.2019.12.005. Epub 2019 Dec 7.
Botulinum toxin (BT) drugs were introduced in the late 1980s. They are now used worldwide in a large number of indications. This huge market and its future opportunities have attracted a number of companies about to enter the competition with projects to develop new BT drugs. We want to outline features of BT drugs that are relevant for their therapeutic use and - with that - are also relevant to compare and to evaluate new BT drugs and to guide their further development. BT drugs may vary in their content of botulinum neurotoxin, complexing proteins and excipients. Their manufacturing is complex and directly influences core features of the final drug. It includes breeding, purification, botulinum neurotoxin activation, stabilisation, potency control, labelling and testing, specific biological activity and packaging. The manufacturer's support concerning product documentation and support, reliability of drug supply, counterfeit protection and - last but not least - competitive pricing is also important. Further developments include the indication spectrum, the market penetration, the drug's duration of action, liquid preparations, transdermal applications, improving antigenicity and a bio-similarity registration process. Most projects, however, will try to produce Botox® analogs at reduced sale prices.
肉毒毒素(BT)药物于 20 世纪 80 年代末问世。如今,它们在全球范围内被广泛用于大量适应症。巨大的市场及其未来的机遇吸引了许多即将进入竞争的公司,开展开发新型 BT 药物的项目。我们想概述 BT 药物的一些相关特性,这些特性对其治疗用途至关重要,也有助于对新型 BT 药物进行比较和评估,并指导其进一步开发。BT 药物在肉毒神经毒素、络合蛋白和赋形剂的含量上可能存在差异。其生产过程复杂,直接影响最终药物的核心特性。它包括培养、纯化、肉毒神经毒素激活、稳定、效价控制、标记和测试、特定生物学活性和包装。制造商在产品文件和支持、药物供应可靠性、防伪以及——最后但同样重要的是——有竞争力的定价方面的支持也很重要。进一步的发展包括适应症范围、市场渗透率、药物作用持续时间、液体制剂、透皮应用、提高抗原性和生物相似性注册过程。然而,大多数项目都将试图以更低的销售价格生产肉毒杆菌毒素(Botox®)类似物。