Investigational Medical Devices

UVA HRPP SOP: Section 13:  FDA Regulated Research

See the UVA Human Research Protection Program (HRPP) Standard Operating Procedure (SOP) Section 13 titled FDA Regulated Research for additional information.

 BACKGROUND

This guidance is intended to assist investigators in meeting the FDA requirements when investigating medical devices in clinical research and in some treatment situations. Federal regulation 21 CFR 812 defines the requirements for clinical investigations of medical devices.

All clinical investigations of devices must have an approved IDE (Investigational Device Exemption) from the FDA or be exempt from the IDE regulations before beginning a clinical investigational of a significant risk device. An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification 510(k) submission to FDA. 

DEFINITIONS

Medical device is defined, in part, as any health care product that does not achieve its primary intended purposes by chemical action or by being metabolized. Medical devices include, among other things, surgical lasers, wheelchairs, sutures, pacemakers, vascular grafts, intraocular lenses, and orthopedic pins. Medical devices also include diagnostic aids such as reagents and test kits for in vitro diagnosis (IVD) of disease and other medical conditions such as pregnancy. A medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is:

• recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
• intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
• intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes (21 U.S.C. 321(h)).

Investigational device means a device, including a transitional device, that is the object of an investigation. A medical device is considered investigational if either condition applies:

• The device is not approved for marketing in the United States or
• The device is approved for marketing but is being clinically evaluated for a new indication.

Investigational device exemption (IDE) IDE refers to the regulations under 21 CFR 812. An approved IDE means that the IRB (and FDA for significant risk devices) has approved the sponsor’s study application and all the requirements under 21 CFR 812 are met.

Significant risk device means an investigational device that:

(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;

(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;

(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

A Non-significant Risk (NSR) device study is one that does not meet the definition for a Significant Risk device study.

IDE Exempt means a study that is exempt from the requirements of regulations under 21 CFR 812. Two common investigations of medical devices that are exempt from the requirement for an IDE include:

• Investigations conducted with legally marketed devices used according to labeling.
• Studies using in vitro diagnostic devices labeled “for research purposes only” may be IDE-Exempt as per regulations if the testing:
  • Is noninvasive;
  • Does not require invasive sampling procedures that presents significant risk;
  • Does not introduce energy into a subject; and
  • Is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure

The IRB then will make an independent assessment of the risk of the investigational device to be used in the study. If the IRB agrees that the devices poses no significant risk to research subjects, the investigator will not be required to obtain an IDE from the FDA to conduct the study. If the IRB instead believes that the device poses significant risk to research subjects, the investigator will be notified by the IRB. The investigator in turn is required to notify the sponsor of the IRB's decision, and the sponsor must notify the FDA of the IRB determination regardless of whether the study is ultimately conducted at UVA. Investigational devices determined by the IRB to poses significant risk to research subjects, will be reviewed according to the requirements described below. 

STEPS TO DETERMINE IF AN IDE IS REQUIRED FROM THE FDA

1. Determine if something is a medical device according to the federal definitions.

Review the definitions of device/medical device above to make this determination.

It is important to remember that apps may be considered a device. See additional information under Exemption.  

2. If the device is determined to be a medical device according to the federal definitions, then determine if the device is exempt from FDA regulations. 

Devices that are exempted from 21 CFR 812 are described in §812.2(c) of the IDE regulation include: 

1. a legally marketed device when used in accordance with its labeling 
    
2. a diagnostic device if it complies with the labeling requirements in §809.10(c) and if the testing:
   • is noninvasive; *
   • does not require an invasive sampling procedure that presents significant risk; 
   • does not by design or intention introduce energy into a subject; and 
   • is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure; 
   • For a diagnostic device, IRB approval is required and no Investigational Device Exemption application must be made to the FDA. In addition, the IRB is not required to make any further determinations related to risk at the time of approval.
   • Penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or the urethra, or enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os.
   • Blood sampling that involves simple venipuncture is considered noninvasive, and the use of surplus samples of body fluids or tissues that are left over from samples taken for non-investigational purposes is also considered noninvasive.
3. consumer preference testing, testing of a modification, or testing of a combination of devices if the device(s) are legally marketed device(s) [that is, the devices have an approved PMA, cleared Premarket Notification 510(k), or are exempt from 510(k)] AND if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk;
    
4. a device intended solely for veterinary use; 
    
5. a device shipped solely for research with laboratory animals and contains the labeling "CAUTION – Device for investigational use in laboratory animals or other tests that do not involve human subjects." 
    
6. a custom device **
   • (1) Necessarily deviates from devices generally available or from an applicable performance standard or premarket approval requirement in order to comply with the order of an individual physician or dentist;
     (2) Is not generally available to, or generally used by, other physicians or dentists;
     (3) Is not generally available in finished form for purchase or for dispensing upon prescription;
     (4) Is not offered for commercial distribution through labeling or advertising; and
     (5) Is intended for use by an individual patient named in the order of a physician or dentist, and is to be made in a specific form for that patient, or is intended to meet the special needs of the physician or dentist in the course of professional practice.
7. Computer programs may be medical devices - it depends on the specific program and exactly what it does. A determination for whether or not a product is a medical device can be obtained by submitting a 513(g) request for classification. More information can be found at http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/ucm127147.htm
8. Medical Mobile Apps: Mobile medical applications (apps) may be considered a device. See examples below.

Examples of medical apps which are considered a device and thus regulated by the FDA:

• Mobile apps that perform patient-specific analysis and provide patient-specific diagnosis, or treatment recommendations.
• Apps that use patient-specific parameters and calculate dosage or create a dosage plan for radiation therapy;
• Computer Aided Detection software (CAD);
• Image processing software24; and 
• Radiation therapy treatment planning software 25.

Examples of medical apps which are NOT considered a device and thus are NOT regulated by the FDA:

Mobile apps that perform simple calculations routinely used in clinical practice - These are apps that are intended to provide a convenient way for clinicians to perform various simple medical calculations taught in medical schools and are routinely used in clinical practice. These apps are generally tailored for clinical use but retain functionality that is similar to simple general-purpose tools such as paper charts, spread sheets, timers or generic mathematical calculators. 

• Body Mass Index (BMI)
• Total Body Water / Urea Volume of Distribution
• Mean arterial pressure
• Glasgow Coma Scale score
• APGAR score
• NIH Stroke Scale
• Delivery date estimator

For additional information see:

• FDA Guidance on Mobile Medical Apps- 9-23 13 
• Guidance on Electronic Storage of Highly Sensitive Data Policy