Significance: The modern use of fluorescence in surgery came iteratively through new devices and pre-existing imaging agents, with indications that were paved via regulatory approvals and device clearances. These events led to a growing set of surgery subspecialty uses. Aim: This article outlines the key milestones that initiated commercially marketed systems and agents by highlighting temporal sequences and strategic decisions between them, with the goal of helping to inform future successes. Approach: A review of successful regulatory approvals and the sequences between them was completed for companies that achieved US Food and Drug Administration (FDA) premarket approval or new drug approvals (NDAs) or device clearances in the fields of fluorescent imaging agents, open surgery imaging devices, and their approved medical indications. Results: Angiography agents, indocyanine green and fluorescein, were approved for human use as absorbing dyes, and this use in retinal imaging was the precursor to lateral translation into tissue perfusion imaging in the last two decades with a growing number of devices. Many FDA cleared devices for open fluorescence-guided surgery used the predicate created by the SPY SP2000 system. This first system was 510(k) cleared for angiography imaging with a unique split predicate from x-ray imaging of vasculature and retinal fluorescence angiography. Since that time, the lateral spread of open surgery devices being cleared for new indications has been occurring with a growth of adoption in surgical subspecialties. Growth into new surgical subspecialties has been achieved by leveraging different NDAs and clearances between indications, such that medical uses have broadened over time. Conclusions: Key decisions made by developers to advance specific device clearances and NDAs have been based upon existing optical fluorescent agents. The historical lessons and regulatory trends in newer indications and contrast agents can help the field evolve via successful investment in new systems and applications.

中文翻译：

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开场荧光引导手术监管审批的成功途径回顾

意义：荧光在外科手术中的现代应用是通过新设备和预先存在的显像剂反复出现的，其适应症是通过监管部门的批准和设备许可铺平的。这些事件导致了越来越多的外科亚专业用途。目的：本文通过强调它们之间的时间顺序和战略决策，概述了启动商业销售系统和代理的关键里程碑，目的是帮助为未来的成功提供信息。方法：对在荧光成像剂、开放式手术成像领域获得美国食品和药物管理局 (FDA) 上市前批准或新药批准 (NDA) 或设备许可的公司完成对成功监管批准及其之间顺序的审查设备及其批准的医疗适应症。结果：血管造影剂、吲哚菁绿和荧光素被批准作为吸收染料用于人类，这种在视网膜成像中的使用是过去二十年随着设备数量不断增加而横向转化为组织灌注成像的先驱。许多 FDA 批准的开放式荧光引导手术设备都使用 SPY SP2000 系统创建的谓词。第一个系统已获得 510(k) 许可，可用于血管造影成像，具有来自脉管系统 X 射线成像和视网膜荧光血管造影的独特分离谓词。从那时起，随着外科亚专业的采用不断增加，开放式手术设备的新适应症正在横向传播。通过利用不同的新药申请和适应症之间的许可，实现了新外科亚专科的发展，因此医疗用途随着时间的推移而扩大。结论：开发人员为推进特定设备许可和新药申请而做出的关键决策是基于现有的荧光剂。新适应症和造影剂的历史教训和监管趋势可以通过对新系统和应用的成功投资来帮助该领域发展。