The immense cost of developing safe and effective medical treatments can mean that rare diseases go without new therapies. The Food and Drug Administration (“FDA”) has taken several approaches to try and encourage the discovery and use of new technologies in these circumstances. One such approach is the creation of a unique pre-market approval process for medical devices intended to treat serious conditions that only affect a limited number of people. This approach has incentivized the industry (and has improved a clinician’s ability to potentially treat his/her patients) but it has also created confusion with regards to roles and responsibilities by drawing Institutional Review Boards (“IRBs”), and their expertise in research, into the oversight of the practice of medicine. Quorum Review, with its regulatory expertise, understands these roles and responsibilities and can guide clinicians and facilities efficiently through this complex and often foreign landscape.
Humanitarian Use Devices and Humanitarian Device Exemptions
A humanitarian device exemption (“HDE”) is a limited approval for the marketing of a device without any claims of effectiveness and with certain restrictions on its profit and use.1 This limited marketing approval is only available for devices that have been designated a humanitarian use device (“HUD”). A HUD is a medical device intended for the treatment or diagnosis of a condition that affects fewer than 4,000 individuals in the United States per year.2 To approve a HUD for marketing under an HDE, the FDA must determine:
- That the device would otherwise not be available and that there is no comparable approved device available to treat or diagnose the disease or condition (i.e. no alternatives);
- That the probable benefit from the use of the device outweighs the risk of injury or illness, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment (i.e. significant patient need)3
Restrictions on the Use of a HUD from an Investigator and Facility Perspective
IRB approval is required before a HUD can be used at a facility with the exception of an emergency use.4 The HDE holder is responsible for ensuring that each HUD is administered only in facilities that have an IRB and which that IRB has agreed to oversee the use of the HUD. This responsibility for oversight may be designated to a non-local IRB if desired.
Investigators and facilities must also submit medical device reports to the IRB, the manufacturer, and the FDA whenever a HUD may have caused or contributed to a death and must submit reports to the manufacturer whenever a HUD may have caused or contributed to a serious injury.
The Role of Institutional Review Boards
IRBs are responsible for initial as well as continuing review of a HUD. For initial review of a HUD, IRBs are required to perform their review at a convened meeting.5 The IRB that reviews and approves the research must be acting in accordance with the FDA’s regulations governing IRBs and should follow the standard review requirements and determinations as much as possible.6
The IRB may nonetheless attach specific limits to the use of a HUD at a facility. For example, an IRB may limit the use of the device based upon a predefined number of cases, the prior use and failure of an alternative treatment modality, the prior reporting of each new potential patient to the IRB, or a requirement to follow certain evaluations.
The Possible Different Uses of a HUD and the Corresponding Regulatory Obligations
The use of a HUD within its market approval only is not research; rather, it is the use of a legally marketed device. Neither Informed consent nor a protocol is required. An IRB may, however, choose to require these materials as a condition precedent to its review.
The use of a HUD outside its market approval for treatment only is also not research. It is the use of a legally marketed device in the practice of medicine. An IRB may, however, choose to prohibit off label uses as part of its initial approval.
The use of a HUD within its market approval in conjunction with efforts to collect data regarding safety and effectiveness is the use of a legally marketed device and an exempted clinical investigation. The FDA regulations for the protection of human subjects (21 CFR Part 50) and IRB review (21 CFR Part 56) will apply, but the regulations for the use of an investigational device (21 CFR Part 812) will not.
The use of a HUD outside its market approval in conjunction with efforts to collect data regarding safety and effectiveness is a clinical investigation. The FDA regulations for the protection of human subjects, IRB review, and the use of an investigational device will all apply.
The use of a HUD to prevent death or serious harm without sufficient time to obtain IRB approval may qualify as an emergency use and may proceed without prior IRB approval, but with as many patient protective measures as possible.7
Submitting a HUD to Quorum Review
Quorum Review requires at least the following materials to review the use of a HUD within its market approval:
- a copy of the HDE approval order;
- a description of the device;
- the product labeling;
- the patient information packet that may accompany the HUD; and
- a summary of how the clinician proposes to use the device, including a description of any screening procedures, the HUD procedure, and any patient follow-up visits, tests, or procedures.
Quorum Review on a case-by-case basis may also require development of an informed consent document and a protocol. This will depend on the complexity of the condition or device and whether additional protections are deemed necessary to protect the rights, safety, and welfare of patients.
A clinical investigation of a HUD must be submitted like any other clinical investigation and may require an investigational device exemption in order to receive final approval.
Quorum Review is committed to helping to bring new treatment options to patients in significant need and welcomes the opportunity to partner with clinicians and facilities to act as the IRB of record and provide the necessary oversight for the use of HUDs.
 FDA Training, Compassionate and Emergency Use of Devices