Frequently Asked Questions About Medical Device Studies

A device is an instrument, machine, implant, in vitro reagent, or other similar article that:

• is intended for use in the diagnosis, treatment, or prevention of disease – and –
• does not achieve its primary intended purpose through chemical action in the body or by being metabolized.

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect the safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k) submissions require clinical study data.

Premarket approval (PMA) is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. PMA is the most stringent type of device marketing application required by FDA.

Devices are classified according to the degree of difficulty in assuring their safety and effectiveness.

• Class I – devices with the lowest risk, such as scalpels, bandages, examination gloves, and nonprescription sunglasses. Safety and effectiveness can be assured by compliance with “general controls.”
• Class II – intermediate risk devices, such as infusion pumps, nebulizers, and spirometers. Class II devices are subject to both “general controls” and “special controls.” Most Class II devices require a 510(k) submission for premarket review and clearance by FDA.
• Class III – devices with the greatest risk, such as life-sustaining, life-supporting, or implantable devices, or those that have a new intended use or employ a new, unique technology. Class III devices require a PMA application. Approval is based on a determination by FDA that the application contains sufficient valid scientific evidence to assure that the device is safe and effective for its intended use.

The sponsor of a significant risk device study is responsible for submitting an IDE application to FDA and obtaining Institutional Review Board (IRB) review and approval before the study can begin.

Study approval must be obtained prior to enrolling patients at the study site. Each site must have approval from the reviewing IRB for that site prior to beginning the study. For significant risk device studies, in addition to IRB approvals, the sponsor must also have an approved IDE from FDA prior to beginning the study at any site. Applications to FDA and to the IRBs are reviewed independently and, therefore, may be submitted simultaneously.

A significant risk (SR) device presents a potential for serious risk to the health, safety, or welfare of a subject. Significant risk devices may include implants, devices that support or sustain human life, and devices that are substantially important in diagnosing, curing, mitigating or treating disease or in preventing impairment to human health. Examples include sutures, cardiac pacemakers, hydrocephalus shunts, and orthopedic implants.

Nonsignificant risk (NSR) devices are devices that do not pose a significant risk to the human subjects. Examples include most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and Foley catheters. A nonsignificant risk device study requires only IRB approval prior to initiation of a clinical study.

General Controls are regulations that apply to all three classes of medical devices to ensure their safety and effectiveness. General Controls include registration and listing, labeling, and Good Manufacturing Practices (GMPs). Full details can be found on FDA’s Center for Devices and Radiologic Health (CDRH) website.

Special Controls may include mandatory performance standards, special labeling requirements, postmarket surveillance, and any other actions FDA deems necessary to assure safety and effectiveness.

A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device that is not subject to PMA. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims.

The legally marketed device to which equivalence is drawn is known as the predicate device.

Substantial equivalence means that the new device is at least as safe and effective as the predicate.

FDA has exempted almost all Class I devices from the premarket notification requirement. However, the manufacturers of these devices are required to register their establishment and list the generic category or classification name. In most instances they must also comply with GMPs.

A Humanitarian Use Device (HUD) is a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.

To obtain approval for an HUD, a Humanitarian Device Exemption (HDE) application is submitted to FDA. An HDE is similar in both form and content to a PMA application, but is exempt from the effectiveness requirements of a PMA. An HDE application, however, must contain sufficient information for FDA to determine that:

• the device does not pose an unreasonable or significant risk of illness or injury
• the probable benefit to health outweighs the risk of injury or illness from its use

The applicant must also demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market. FDA approval of an HDE authorizes an applicant to market a HUD subject to certain profit and use restrictions. HUDs cannot be sold for profit, except in narrow circumstances.