Review of successful pathways for regulatory approvals in open-field fluorescence-guided surgery.

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.