Regulatory and Safety Issues Surrounding Hepatic Arterial Infusion Devices: The Past, Present, and Future

After the initial administration of intrahepatic chemotherapy in humans with colorectal cancer liver metastases in the 1970s, numerous devices have been used, ranging from mechanical external pumps to implanted body heat-driven pumps with non-modifiable flow rates, to battery-driven fully programmable Bluetooth-enabled electronic pumps. For most of these pumps, prior to widespread usage, regulatory approval was obtained through standard processes. However, in 2018, a unique set of circumstances led to the discontinuation of the only available FDA-approved pump at the time, the Codman 3000, leaving no available approved devices to deliver hepatic arterial infusion (HAI) chemotherapy that many patients needed. Some institutions closed their pump programs, while others used an off-label device combination, the Medtronic Synchromed II pump combined with the Codman vascular catheter, which was still available. Still others, including our own institutions, placed the hybrid device off-label at first through individual Emergency and Compassionate Use Authorizations through the FDA, before initiating formal safety clinical trials under Investigational Device Exemptions. In 2020, this issue became moot when the Codman 3000 pump became available again with FDA approval, renamed as the Intera 3000 pump. We review here the complex regulatory history of HAI devices, and discuss the general process of device approval as well as mechanisms of off-label device usage.