As the national organ transplant waiting list continues to grow and donation and transplant rates remain stagnant, the US Food and Drug Administration (FDA) on Thursday released new draft guidance to help industry with recommendations on best practices for animal studies used to evaluate organ preservation devices.
The shortage of organs available for transplants has propelled a new wave of organ preservation technologies, FDA says, noting that these technologies are evaluated in animal models to demonstrate that they are suitable for clinical use.
FDA says most of these animal studies will be submitted to support investigational device exemption (IDE) applications, though they may also be used to support premarket approval (PMA) applications, premarket notifications (510(k)), humanitarian device exemption (HDE) applications or de novo classification requests.
Most of the devices to which this guidance applies are currently not classified, FDA says.
But the recommendations are "applicable to the product code KDN, System, Perfusion, Kidney (21 CFR 125 876.5880, Class II)" but "do not apply to devices intended to preserve organs via cold static storage, including those associated with product codes KDK, PIN, KDL, and MSB, regulated as Class II devices," or human cells, tissues and cellular and tissue-based products (HCT/P’s) or the devices utilized to preserve and transport them.
FDA says that a typical experimental setup for such animal studies will include three phases: organ procurement, organ preservation and organ reperfusion.
Following the procurement from appropriate donors, organs are preserved "using either an experimental method (e.g., machine perfusion) or a control method (e.g., cold static storage)," FDA notes. "Organs from both groups are reperfused in either an in vivo or ex vivo model, to evaluate reperfusion injury," and this reperfusion phase is discussed in detail in the draft.
The agency also notes transportability and contamination, saying that compared to cold static storage, machine perfusion "has a higher risk of contamination due to the increased complexity of the perfusion circuit and manipulation of the organ. Therefore, FDA recommends performing bacterial cultures on perfusate samples taken at the end of a perfusion session to demonstrate contamination did not occur."
The guidance closes with: "While FDA understands that, the choice of the model may be restricted by many factors including utilizing animals and other available resources, your study should primarily be based on the study objectives and the risks of the device. For instance, in vivo models may be necessary to support an IDE application for a perfusion solution with multiple novel components or a first-of-its-kind device indicated to improve the quality of extended criteria donor organs. Ex vivo models may be sufficient to support, for example, a device modification or protocol modification of a previously approved IDE. Recognizing that each scenario is unique and that our understanding of these devices continues to evolve, FDA recommends that you engage us via the Pre-Submission process to obtain feedback on proposed animal studies."