In 2009, the FDA launched the 515 Program Initiative to classify high-risk devices such as intra-aortic balloon pumps, ventricular leads and automated external defibrillators.

It was the latest measure since the Medical Device Amendements of 1976 required high-risk devices such as replacement heart valves and implantable pacemakers undergo FDA review before marketing via the premarket approval pathway. At the time, the FDA did not have the time or staff to conduct all premarket approval reviews, so Congress allowed the high-risk devices to be temporarily regulated through the 510(k) pathway for moderate-risk devices.

Still, the 510(k) pathway remained in place for years afterward until the 515 Program Initiative was finally passed, according to three researchers who explained the initiative online in JAMA Cardiology on March 9.

The authors were Vinay K. Rathi, BA, of the Yale University School of Medicine in New Haven, Conn.; Aaron S. Kesselheim, MD, JD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston; and Joseph S. Ross, MD, MHS, of the Yale University School of Medicine.

They used the Impella 2.5 percutaneous ventricular assist device (Abiomed) as an example of the process manufacturers must go through to market a device.

In May 2008, Abiomed obtained a 510(k) clearance for the Impella. The FDA reviewed data on nonroller cardiopulmonary bypass pumps, which Abiomed claimed the Impella was similar to in terms of safety and efficacy. The agency also assessed the risks and benefits of percutaneous ventricular assist devices by performing a systematic review.

After completing its review, the FDA said non-roller bypass pumps should be classified as moderate-risk and the Impella and other percutaneous ventricular assist devices should be classified as high-risk.

In December 2012, the FDA convened an advisory committee that voted 10 to 3 in favor of the revised classification. In 2014, two months after the FDA officially proposed the classification, Abiomed sought a premarket approval for the Impella through the 515 Program Initiative.

Based on the results of three studies, the FDA determined that the Impella likely offered clinical benefit compared with intra-aortic balloon pump therapy. As part of the premarket approval of the Impella in March 2015, the researchers noted that the FDA required Abiomed to conduct a prospective, multicenter, single-group study in 369 patients.

Rathi, Kesselheim and Ross mentioned that researchers could not assess large-scale, real-world outcomes of the Impella using electronic health records and administrative claims data because it was not possible to identify which percutaneous ventricular assist device patients receive.

They also said that there is publication bias in the biomedical literature and that registries cannot normally assess long-term outcomes and typically underreport adverse events.

“The FDA deserves applause for the important steps it has taken in modernizing device regulation to ensure all high-risk devices undergo clinical testing,” the researchers wrote. “Though the FDA faces the difficult task of requiring meaningful evidence for approval without placing undue burden on manufacturers, these last preamendment devices being considered through the 515 Program Initiative are already in widespread use, suggesting that there should be ample opportunity for manufacturers to conduct large, robust clinical studies examining patient-important outcomes to ensure that patients and physicians may continue using these high-risk devices with assurance of their safety and effectiveness.”