Regulatory Pathway for Home Hemodialysis Devices in the United States

In 1972, when the Medicare Act provided people in the United States with coverage for renal replacement therapy, 40 percent of patients were doing home hemodialysis (HHD). In 2003, only 0.7 percent of the dialysis population in this country were doing HHD. The Aksys Company was founded in January 1991 to develop an HHD machine that would be patient friendly; reduce the labor of setting up, putting on, and tearing down; provide ultrapure water; and reuse the dialyzer and blood tubing to reduce cost. Since then, the following advances in HHD devices have continued to evolve.

The Center for Devices and Radiological Health (CDRH) of the U.S. Food and Drug Administration (FDA) is responsible for the regulation of medical devices in the United States. For a new device to be released into interstate commerce (i.e., marketed), CDRH must determine whether there is a reasonable assurance of safety and effectiveness of the proposed device based on valid scientific evidence.

While a review of medical device regulation is beyond the scope of this article, traditional hemodialysis systems are regulated as Class II Medical Devices and require “clearance” from the FDA before they can be marketed. Clearance is obtained via the submission of a premarket notification to FDA. These filings are commonly referred to as “510(k) submissions,” named after the relevant section of the Food, Drug, and Cosmetic Act.

A premarket notification, more commonly referred to as 510(k), must demonstrate that a proposed device is substantially equivalent (at least as safe and as effective) to a device that is legally marketed for the same use. The legally marketed device to which equivalence is drawn is commonly known as the “predicate” device. Submitters need to provide a comparison of the proposed device to the predicate and provide testing and a scientific rationale that supports substantial equivalence of the two devices. Once a device has been demonstrated to be substantially equivalent to the predicate device, it can be “cleared” for marketing by FDA.

For traditional hemodialysis systems, the recommended testing to support substantial equivalence should include functional testing that demonstrates that the device performs as designed and expected, a system-level hazard analysis that confirms that the device does not perform in an unexpected and/or unsafe manner, software validation, electrical safety testing, electromagnetic compatibility testing, biocompatibility testing, and sterility and disinfection validation. A full summary of testing recommendations can be found in the 1998 FDA Guidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems (1).

For hemodialysis systems intended to be used in the home environment, FDA has typically requested the inclusion of additional performance information, including human factors validation (usability testing) and clinical performance data for this different use environment (24). While FDA does not have a specific guidance document for the content of a premarket notification for a home hemodialysis delivery system, the 2008 FDA Guidance for Investigational Device Exemptions (IDEs) for Devices Indicated for Nocturnal Home Hemodialysis includes useful additional information (5). While this document was intended to outline recommendations for nocturnal home hemodialysis, it includes concepts that may be useful to home hemodialysis therapies in general.

For example, this document outlines FDA recommendations for human factors validation and clinical study design. As stated in the guidance, clinical studies for home hemodialysis systems should include an evaluation of the incidence of adverse events, the device’s ability to deliver prescribed treatments, and the subject’s or care partner’s ability, after appropriate training, to conduct the prescribed treatments in a home setting (5). As an example, a previous clinical study utilized a crossover design, including a comparison of assessments for subjects over a period of time in-clinic, followed by a transition period, and then a period of home use (6). Of note, the overall goal of clinical studies to demonstrate home use for hemodialysis systems has been to support that the device is at least as safe and as effective as the predicate, with more of a focus on the actual device and delivery system and less of a focus on the hemodialysis treatment modality (i.e., short daily vs. conventional thrice weekly hemodialysis).

CDRH is aware that the emergence of new technologies sometimes challenges the current regulatory paradigm and has several ongoing initiatives to promote innovation. In January 2012, as part of FDA’s Innovation Pathway, CDRH announced the Innovation Challenge, which was a pilot program for early phase collaboration with FDA for innovative devices that could have a significant impact on the public health. End stage renal disease (ESRD) was chosen as a focus for this challenge given that ESRD is managed almost entirely using medical devices, and because it was thought that the ESRD community could benefit from innovative devices and transformative improvements given the overall negative impact of ESRD on a patient’s quality of life. Additional information on the ESRD Innovation Challenge can be found at http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHInnovation/default.htm.

Two novel hemodialysis systems were selected as part of this challenge, an implantable hemodialysis system and a wearable hemodialysis system, at varying early stages of development (7). While not home therapies in the traditional sense, these and other innovative technologies will continue to challenge our current thinking and regulatory processes with the ultimate goal of assuring that patients and providers have timely and continued access to safe, effective, and high-quality medical devices. However, as these new technologies emerge, CDRH encourages early interaction with the agency during the device development process. Additional guidance for obtaining agency feedback for regulatory questions related to a planned submission can be found in the 2014 FDA guidance Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff (8).

References

1. 

U.S. Department of Health and Human Services. Guidance for the Content of Premarket Notifications for Hemodialysis Delivery Systems. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080164.pdf.

2. 

U.S. Food and Drug Administration. http://www.accessdata.fda.gov/cdrh_docs/pdf/k010131.pdf.

3. 

4. 

5. 

U.S. Department of Health and Human Services. Guidance for Industry and FDA Staff: Investigational Device Exemptions (IDEs) for Devices Indicated for Nocturnal Home Hemodialysis. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071150.pdf.

6. 

Kraus M, et al. A comparison of center-based vs. home-based daily hemodialysis for patients with end-stage renal disease. Hemodial Int 2007; 11:468–477.

7. 

8. 

U.S. Department of Health and Human Services. Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176.pdf.