Adagio Ablation Case Shows How FDA Expanded Access Works for Unapproved Devices

Adagio Medical said a physician at the Hospital of the University of Pennsylvania has treated the first patient with its next-generation vCLAS Ultra system, an ultra-low temperature cardiac ablation device, under expanded access authorization from the US Food and Drug Administration, Medical Economics reported on Aug. 3. According to the company, the patient's ventricular tachycardia had not responded to radiofrequency ablation or coronary venous alcohol ablation.

The physician is an investigator in Adagio's FULCRUM-VT pivotal investigational device exemption trial, and FDA has granted IDE approval to expand that trial to evaluate the vCLAS Ultra system in sustained monomorphic ventricular tachycardia, the report said. The company said preclinical data suggest the new version could cut ablation time by 50% to 75% compared with its first-generation system. The report did not say which expanded access mechanism was used.

Three routes outside a trial

FDA's expanded access page for devices describes the program as a potential pathway for patients with a serious or life-threatening disease or condition to access an investigational device that has not been approved or cleared, for treatment outside clinical trials, when no comparable or satisfactory alternative is available. It works through three mechanisms.

Emergency use covers an individual patient in a life-threatening situation who needs immediate treatment, with no alternative and no time to seek FDA approval. FDA says an unapproved device may then be used without prior agency approval, provided the criteria are met. The physician is expected to judge that the criteria apply and to follow as many patient protection procedures as possible. If an IDE exists, its sponsor must notify FDA within five days; if not, the physician should send FDA a follow-up report within five days.

Compassionate use covers an individual patient, or a small group, with a serious disease or condition and no satisfactory alternative, where the potential benefit justifies the risks of the investigational device. It can apply to patients who do not meet a trial's entry criteria, or to devices with no trial at all. When an IDE exists, the IDE sponsor files a supplement describing the patient's condition, why alternatives are unsatisfactory and any protocol deviations. FDA says such requests have the same statutory 30-day review cycle as other IDE submissions but are reviewed, on average, within 15 days. The physician should not treat the patient until FDA approves, and a follow-up report is due within 45 days of use.

Treatment IDEs cover larger groups. They apply when the device is intended for a serious or immediately life-threatening condition, no comparable or satisfactory alternative exists, the device is under study in a controlled trial for the same use or all trials are complete, and the sponsor is pursuing marketing approval with due diligence.

What expanded access does not do

Expanded access depends on the manufacturer. FDA states that if a physician wants an investigational device for an individual patient, the company must first agree to provide it, and that “The FDA cannot require a company to provide an investigational device for compassionate use to proceed.”

Nor does it substitute for a marketing decision. In reviewing compassionate use requests, FDA says it considers whether preliminary evidence of safety and effectiveness justifies the use and whether the use would interfere with a clinical trial meant to support marketing approval. A treatment IDE, the agency says, can also be used to gather more data on a device's safety and effectiveness.