Hi, I'm Kim Selzman. I'm a cardiac electrophysiologist and the chief of cardiology at the Salt Lake City VA, and I'm also chair of the Health Policy Committee. We're very glad that you could join us today for our mini session on device reprocessing and reuse. It seems there's always interest in the topic of device reuse, and I think it's because we as electrophysiologists recognize what a precious and expensive resource that these devices are. There has been some interest recently in some of the HRS online discussions, and so we thought it would be very timely to have some talks on device reprocessing and reuse as part of the HRS 2020. We're going to hear from Dr. Lewis. He's an electrophysiologist who has worked at the Food and Drug Administration, or FDA, for many years and has really become one of the go-to point persons if you have any regulatory questions on device reprocessing and reuse. We'll also hear from Dr. Crawford, an electrophysiologist at the University of Michigan, and he's worked really hard with his colleagues to create a device reprocessing center and the infrastructure to get these devices donated to them, reprocess them, meaning cleaning the devices and then doing bench testing to make sure the devices are functioning properly, and then figure out how to get these devices to patients in need in various countries around the globe. So thanks for joining our session. Hello, this is Captain Brian Lewis of the U.S. Public Health Service. I am a medical review officer for FDA's Office of Product Evaluation and Quality, Office of Health Technology II, which is the cardiovascular devices group at U.S. Food and Drug Administration. I have been working with the implantable electrophysiology devices team at FDA for the last 16-plus years, including more recent work on reprocessing and exporting pacemakers in conjunction with Heart Rhythm Society. I will be speaking on behalf of the U.S. Food and Drug Administration on legal export of reprocessed pacemakers, how to export, and color inside the lines. For reference, in the context of this talk, the term pacemaker refers to a pacemaker pulse generator. Reprocessing refers to a pacemaker pulse generator that has been explanted after limited use, such that there is substantial remaining battery charge. Reprocessing includes cleaning and verification of pacemaker function. Each year that I review the reprocessing and export regulations, I consult with FDA's subject matter experts. These include Layla Lawrence in the Office of Regulatory Programs and Tanya Farouk in the Office of Health Technology II. My thanks to these colleagues. I have no conflicts of interest. More than in previous years, I would like to emphasize that legal export of pacemakers from the United States to needy countries is regulated by FDA and can be accomplished by practicing heart rhythm cardiologists, institutions, and groups because regulatory requirements are limited. Legal export of pacemakers has been successfully accomplished. It entails more than simply collecting pulse generators after use, washing them, and carrying them abroad. The requirements for legal export of pacemakers can be successfully accomplished working with FDA. Heart Rhythm Society members need not have an advanced degree in regulatory science or extensive prior experience to succeed in meeting the limited regulatory requirements necessary to legally export reprocessed pacemakers. As in previous years, I want to emphasize that FDA will work with you to help any interested cardiologist, institution, or group in their efforts to legally export reprocessed pacemakers. All it takes is to start contacting FDA. My contact information is at the bottom of the slide. Interested Heart Rhythm Society members and any member of the Heart Rhythm community can email me. Again, I would like to emphasize that it is not necessary to end-run the regulatory requirements for legal export. They can still be used in the export. They can be accomplished. Please color within the lines of the law. Broadly speaking, the reprocessing of pacemaker pulse generators for export must meet two requirements. First, the degree of safety and effectiveness must not be contrary to public health and safety. This is a significantly lower requirement than that for approval of new pacemakers within the United States. They must meet the bar of reasonable assurance of safety and effectiveness. Second, applicants interested to reprocess pacemakers for export must address the risk of infection and preservation of pacemaker function. FDA asks that applicants submit a protocol specifying how they will accomplish these two steps. This slide provides greater detail on FDA's expectation of exporters for reprocessed pacemakers. Briefly, the regulatory status of all exported pacemaker pulse generators that are reprocessed is that they are not approved for use in the United States. This is because FDA specifically prohibits reprocessing of pacemaker pulse generators for the U.S. market. Applicants must provide a statement that a National Library of Medicine search has been performed, and they must provide a letter from the appropriate foreign liaison, the person who has authority to sign a letter of acceptance from the foreign government, that the device is not in conflict with the laws of the country accepting the devices. The foreign government must also attest that they have full knowledge of the status of the device in the United States, and that they do not object to the import. FDA recommends that protocols for cleaning and functional performance validation are provided to FDA to explain how the low risk of infection and adequate device functionality are assured. In order that we may understand and come to the same conclusion that you do, that export of the reprocessed pacemakers is not contrary to public health and safety. FDA appreciates the opportunity to clarify the legal regulatory requirements necessary for pacemaker reprocessing and export outside the United States to needy countries. Again, you are welcome to explore the FDA website, and it may be easier for you to simply reach out to subject matter experts at FDA. You can begin with an email to me. Thank you very much. Hello, my name is Thomas Crawford, and I really appreciate the opportunity to share with you the University of Michigan experience with pacemaker reuse. Pacemaker reuse. About 10 years ago, we appreciated the vast and unmet need for pacing in developing countries, where many, if not most patients, do not have access to pacemaker therapy. Our work was inspired by a husband of a woman who passed not long after pacemaker implantation at our center. The widower brought the pacemaker removed by the crematory and handed it to one of our fellows at the time, Dr. Tamir Bauman. The gentleman said that his wife would have wanted her pacemaker to bring a new life to another human being, and that's how it started. Our mission is to acquire, reprocess, and provide reconditioned devices free of charge to patients in the developing countries where access to this therapy is very limited. We also want to accrue clinical evidence for safety and efficacy of pacemaker reuse so that it would bolster the development of our legal and regulatory framework, which would allow us to scale up donations to thousands of devices annually. Finally, we want to develop partnerships with centers of excellence in donor and recipient countries so that we can foster a growing network of implanting physicians. Before we begin discussing the reprocessing protocol, I wanted to touch on the issue of longevity. What is the minimum amount of battery life remaining, which we would accept for a donated pacemaker? This, of course, is by definition arbitrary. We thought that a minimum battery of four years would be reasonable. We performed an analysis of the yield of batteries with at least four years remaining among the pacemakers that we received from funeral homes and crematories, and the yield in that device population is about 15%. The yield from hospitals is about 50% when compared to non-ERI procedures, that is, device upgrades, revisions, and infections. About 50% of non-ERI procedures have sufficient battery life remaining. Everything happens per protocol. During the first stage, we receive devices and determine their gross eligibility based on battery estimation and the overall condition of the device. We do not use devices with any indentations or obvious damage. During the second stage of the process, the devices are decontaminated with Enzol solution. It's a detergent, an enzymatic detergent solution. We subsequently do further electrical screening, and we use a standardized test load of 500 ohms. We then remove seal plugs and set screws so that the second decontamination and cleaning can occur. And I will display the process in a couple slides with a picture. We then reinsert the set screws. We perform detailed functionality testing. We replace the seal plugs, and we dip the devices four times in medical-grade silicone. Then the devices are packaged, sterilized, then stored, and they are interrogated just because they're shipped to recipient centers in a developing country. I wanted to share with you several photographs so that you can get a sense of what our work environment is like. World Medical Relief is the location where we do the initial evaluation and cataloging, and in these two photographs you see undergraduate students from the University of Michigan who are volunteering on Saturday mornings to evaluate our devices and to assess their initial battery longevity. These photographs were taken at NE Scientific. This is the company that re-sterilizes, that cleans and re-sterilizes the devices for us. On the left-hand side you see initial cleaning and decontamination. You see what a product is of a seal plug and screw removal, the purpose of which is to be able to clean the header and make it free of any type of blood products or contaminants. The next stage of the process occurs at the World Medical Relief Center where two persons are required to test the devices for their functionality. We can see on this photograph is on the right-hand side you see a programmer which will be used to see what the device is thinking. In the middle of the photograph you see an oscilloscope which is used to measure outputs from the device as we reprogram it. And then finally on the left-hand side you see a heart simulator which is connected to a computer where we developed a program that would actually input electrical signals into the pacemaker so that we could determine whether the pacemaker functions correctly. Some of the things that we test at World Medical Relief are the following. We look at the battery voltage, its impedance, we assess magnet response, we evaluate impedances of the leads, meaning we attach a standardized impedance lead and we make sure that the device is seeing it accordingly. We also assess the pacing rate to make sure that what comes out of the pacemaker is what the pacemaker is programmed to do. We measure the pulse amplitude and pulse width. We perform the sense test, AV-PV delay. We check refractory periods, pulse ventricular HR refractory period, as well as max sensor rate and max tracking rate. So we perform the basic tests of the basic functions of the devices. We do not perform more complex tests which would exceed our ability to do at this point and which would not necessarily be important for the basics of pacing. I also want to show you what our devices are packaged in. They're placed in double Tyrex pouches. They are labeled with a unique serial number. Those are then sterilized and placed in hard boxes with foam. We also performed process validation. This was performed through destructive testing, meaning we sampled a number of devices and we assessed how our process holds up versus those tests. So we did a bioburden test, a protein and hemoglobin residual test, total organic carbon residual. We assessed cytotoxicity, intracutaneous reactivity, pyrogenicity, and ethylene oxide and ethylene chlorohydrin residues. This validation has been published in Jack EP. We also did a mechanical screw cap pull test where we determined that the seal plugs that are placed on top of the set screws and dipped in silicone four times, the force that is required to remove them on average is no different than the force that is required to remove seal plugs as they originally come from the factory. Additionally, we did a high pop test in which we assured that with our processing of placing the seal plugs and dipping the seal plugs in silicone would not result in any current leak through a saline solution. We also performed packaging validation to assure that the packaging would be able to withstand the appropriate challenges from humidity or heat. And this was done in accordance with ISO standards. As I've mentioned, I've described to you the reprocessing protocol for our devices. Our current goal is to continue randomizing patients in a prospective trial of device reuse where we compare brand new devices with reconditioned devices. We also keep a registry of reused pacemakers. Our goals for the future are to raise public awareness. I very much hope that I can attract collaborators from among those of you who are watching this so that we can expand the reach of the program and ultimately scale up the model so that the nonprofit would be able to provide thousands of pacemakers to needy patients free of charge. I would like to thank Dr. Kim Eagle who is my senior colleague and mentor as well as Dr. Tamir Bahman who inspired us to do this work. Sheldon and Miriam Davis who have been very generous with their support as well as our collaborators Eric Peral, Jay Snell, Noah Klugman, Evan Bruce Rogers, Pat Sebringer, and Zahir Yousef. I also want to welcome any inquiries you may have about this project. I would very much look forward to working with you on developing new avenues for our project and saving the lives of patients that otherwise would not have the ability to access a pacemaker therapy. Thank you very much for your attention. You can also check out our work at myheartyourheart.org I want to thank Dr. Lewis and Dr. Crawford for their excellent talks on the regulatory process through the FDA as well as the nuts and bolts of how to reprocess and reuse these devices. From Dr. Lewis's talk it seems to me the take-home points are that reprocessed devices cannot be used in the United States but if you want to export reprocessed devices it can be done it just needs to meet the regulatory requirements delineated by the Food and Drug Administration and your reprocessing process in terms of how you're going to go about cleaning the devices and doing bench testing on the devices and repackaging the devices must be reviewed by the FDA as well and then ultimately you need both a certificate from the United States Food and Drug Administration as well as the foreign government to which you're exporting the devices to. And I really enjoyed Dr. Crawford's talk he really nicely described how their reprocessing is done from cleaning to testing to the repackaging process. He mentioned the WMF the World Medical Relief Organization that they have set up and they have it seems like a nice team of volunteers to help do the testing as well as connections with the re-sterilization company that they can use in order to reprocess these devices. And I really think it's fantastic that they're doing a randomized controlled trial randomizing patients to reprocess devices to be reused versus new devices and I can only imagine how difficult will be to do a study like that in terms of long-term follow-up but I think it's really important to know long-term how these devices are doing in terms of infection rates and device functionality and battery longevity. My understanding from Dr. Crawford is that right now they're just using pacemakers and in terms of what countries they've been able to make connections with they're mostly in Sub-Saharan Africa and as you can see it was it's not easy to go through the regulatory process but they were able to do it with close collaboration with the FDA and it sounds like from Dr. Crawford they had to get have a lot of devices donated to them right now a lot from crematories but one of the biggest hurdles is actually making these connections with foreign governments or health ministries to explain their program and ultimately to obtain the letter of certificate from these foreign countries. So if anyone watching has regulatory questions or wants to learn more about Dr. Crawford's work I really encourage you to contact them directly they both did provide their emails in their talks and the other option is you could post a comment on the health policy community online and we'd be happy to take any questions or comments and we'll address them online. So thanks so much for watching.

device reprocessing

legal export

reconditioned devices

pacemaker reuse

regulatory compliance

collaborations