- FDA issued final guidance Tuesday on a risk-based approach to designing animal tests for evaluation of hypothermic or normothermic machine perfusion organ preservation devices, citing national need for a wider pool of available organ transplants.
- The document lays out considerations for carrying out and evaluating organ procurement, preservation and in vivo and ex vivo reperfusion, or restoration of blood flow, in comparing device effectiveness to a common control method like cold static storage.
- FDA recommends device developers submit a pre-submission to obtain feedback for specific study protocols.
FDA is aiming to support development of technologies that could increase donated organs' chances of survival for transplant.
It is one strategy that could help get more Americans off the transplant waiting list. More than 36,500 transplants were performed in 2018, which the Health Resources and Services Administration called a record high for the sixth consecutive year. But the waiting list has also grown, with 113,000 individuals registered in hopes of receiving a match as of January 2019.
Last week, FDA gave its support to one such device, announcing premarket approval for a technology from Swedish medtech Xvivo Perfusion designed to ventilate and oxygenate donor lungs while pumping the organ with a preservation solution until it can be assessed for transplant.
Standard of care in organ preservation is cold static storage, wherein organs are submerged in a preservation solution in a closed container that maintains hypothermic temperature. Alternatively, machine perfusion, as described by FDA, uses a device that pumps a perfusate and keeps the organ at hypothermic or normothermic temperatures. These devices can also contain oxygenators, heat exchangers, sensors, disposable circuits, and computer units for processing and displaying hemodynamic and metabolic data, FDA said.
The finalized guidance document aims to give industry clarity on how to best design animal studies sufficient for evaluating these machine perfusion devices, which can then be used to support investigational device exemption (IDE) applications, and ultimately other premarket applications like 510(k)s, De Novos and PMAs.
FDA recommends carefully considering procedure duration in the procurement, preservation and reperfusion phases, noting timing can significantly impact the outcome of transplant studies, and that preservation time may differ across organ types.
The agency also notes that machine perfusion presents a higher risk of contamination because of "the increased complexity of the perfusion circuit and manipulation of the organ," meaning companies ought to perform bacterial cultures on perfusate samples taken at the end of a session.
Organ transport is also a concern, FDA said, recommending the use of animal testing to assess whether a preservation device and an organ may be able to withstand turbulence or tilting during an ambulance ride, for example, which could alter the organ support system or change perfusion parameters.
FDA lays out the two models for assessing reperfusion injury. The in vivo model is when the organ is transplanted into a recipient animal, a method that may be necessary to support an IDE application for a first-of-its-kind device or a perfusion solution with multiple novel components. The ex vivo model involves an organ being reperfused in an isolated setup, which may be sufficient to support a device modification or protocol modification to a previously approved IDE application.
The agency said it sees value in both models, calling them not mutually exclusive, as in vivo models can be used to verify findings from ex vivo models.