The FDA yesterday bestowed the rare accolade of a humanitarian device exemption (HDE) approval on Xvivo Perfusion’s lung transplant technology. HDEs are roughly the medtech equivalent of orphan drug approvals, and are awarded to devices that treat conditions affecting fewer than 4,000 people in the US each year.
The first half of this year was devoid of HDE approvals, despite a rapid uptick in the rate at which first-time premarket approvals (PMAs) were handed out (FDA grants twice as many device approvals in half the time, July 25, 2014). With only two HDEs awarded in 2013 and none at all in 2012 (see table below), the fact that the Xvivo system has achieved the distinction points to the value the FDA places on the technology. The company’s shares are up 12% today on the Stockholm exchange.
Improving the odds
The technology could well be very important. The shortage of donor organs for transplant is a pressing concern: according to the FDA, 1,754 lung transplants were performed in the US in 2012, after which a further 1,616 potential recipients remained on the waiting list.
The agency is therefore open to devices that might improve the odds. The Xvivo Perfusion System preserves donated lungs that do not initially meet the criteria for lung transplantation, allowing time for a more detailed assessment of the organs. After a more in-depth evaluation the original decision is sometimes overturned, and the lungs are passed as fit for implantation. Currently, only one in five donated lungs is suitable for transplant, the FDA says.
The system comprises an cardiac bypass system including a pump, heater and cooler, and a ventilator; it keeps the lungs at body temperature and continuously perfuses the tissue with Xvivo’s sterile solution to remove waste products. The ventilator enables the airways to be examined with a bronchoscope.
The device went before an FDA advisory committee in March (Event – Xvivo tech aims to breathe new life into transplants, February 17, 2014). The gastroenterology and urology devices panel voted 10-0 on all three votes in favour of safety, “probable benefit” and overall risk-benefit profile.
|HDEs vs PMAs, 2005-2014|
|Year||Number of HDEs||Number of PMAs|
|2014 to date||2||18|
The Xvivo system was not the first HDE approval this year; the FDA quietly conferred one last month on Terumo’s Lvis product line, used in the embolisation of intracranial aneurysms.
HDEs, being intended to address unmet needs, carry a lower burden of proof when it comes to efficacy than PMAs, the other main regulatory route for innovative technologies. An HDE application does not have to contain clinical data demonstrating that the device is effective – though it must show that the probable benefit to health outweighs the risks, as well as satisfying several other conditions.
Xvivo submitted data from two clinical trials to support safety. Both compared lung transplant patients who received non-ideal donor lungs preserved using Xvivo’s device with patients who received ideal donor lungs preserved using conventional techniques. Both trials showed that recipients of the ideal and non-ideal lungs had similar survival rates up to 12 months after transplant and similar rates of organ rejection. Xvivo will supplement this with a post-approval study.
Even though relatively little evidence is needed, very few devices manage to achieve this kind of approval – the last decade has seen 23 HDE approvals compared with 297 first-time PMAs, data compiled by EvaluateMedTech show.
And this is no quicker than standard PMA approach. Since 2005, it has taken an average of 18.1 months to shepherd a device down the PMA path, but 23.6 months to obtain an HDE. The FDA awards few HDEs, but it takes its time to review the products.
Quite right too; often the technologies are so novel that the agency has to create new categories for them, which is why the EvaluateMedTech device classification for the Xvivo system has yet to be decided. It is reassuring to know that devices with no forerunners receive a lot of the FDA’s time and attention.
|HDE approvals of the last five years|
|Device name||Company||EMT device classification - level 1||
classification - level 3
|Number||Decision date||Review time (months)|
|NeuRx RA/4||Synapse Biomedical||Anesthesia & Respiratory||Other Respiratory Therapeutic Devices||H070003||17 July, 2008||11.0|
|Levitronix CentriMag right ventricular assist system||Thoratec||Cardiology||Ventricular Assist Devices||H070004||October 7, 2008||17.3|
|Infuse/Mastergraft posterolateral revision device||Medtronic||Orthopedics||Bone Fillers||H040004||October 10, 2008||37.1|
|IBV valve system||Olympus||General & Plastic Surgery||Other Surgical Instruments & Accessories||H060002||October 24, 2008||31.2|
|Reclaim deep brain stimulation for obsessive compulsive disorder||Medtronic||Neurology||Deep Brain Stimulation Devices||H050003||February 19, 2009||39.7|
|Melody transcatheter pulmonary valve and Ensemble delivery system||Medtronic||Cardiology||Transcatheter Heart Valves||H080002||January 25, 2010||16.9|
|cPAX aneurysm treatment system||NeuroVasx||Neurology||Neurovascular Devices||H100002||January 4, 2011||8.3|
|NeuRx diaphragm pacing system||Synapse Biomedical||Anesthesia & Respiratory||Other Respiratory Therapeutic Devices||H100006||September 28, 2011||11.5|
|Elana Surgical KitHUD||Elana||Cardiology||Atherectomy Devices||H080005||October 3, 2011||33.9|
|BSD-2000 hyperthermia system||BSD Medical||Radiology||Hyperthermia Devices||H090002||November 18, 2011||29.8|
|Berlin Heart EXCOR paediatric ventricular assist device||Berlin Heart||Cardiology||Ventricular Assist Devices||H100004||December 16, 2011||17.8|
|Argus II retinal prosthesis system||Second Sight Medical Products||Ophthalmics||Other Ophthalmic Prosthetic Devices||H110002||February 13, 2013||21.4|
|Liposorber LA-15||Kaneka||Blood||LDL Therapeutic Devices||H120005||October 10, 2013||13.2|
|Low-profile visualized intraluminal support device (Lvis and Lvis Jr)||Terumo||Neurology||Neurovascular Devices||H130005||July 25, 2014||Unknown|
|Xvivo perfusion system||Xvivo Perfusion||TBD||TBD||H120003||August 13, 2014||25.1|