Investigational Medical Devices

 

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. 

First one must determine if something is a device according to the federal definitions. Per the statute: Federal Food, Drug, and Cosmetic Act Sec 201.h [21USC321]

DEVICE: The term "device" (except when used in paragraph (n) of this section and in sections 301(i), 403(f), 502(c), and 602(c)) means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is: 

(1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,

(2) 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

(3) 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.

Per FDA Information Sheet Guidance for IRB's, Clinical Investigators, and Sponsors: Frequently Asked Questions About 

Who Must Apply for an IDE?

The sponsor of the clinical trial is responsible for submitting the IDE application to FDA (812.40) and obtaining Institutional Review Board (IRB) approval before the study can begin. Foreign companies wanting to conduct a clinical study in the U.S. MUST have a U.S. sponsor (812.18). Under certain circumstances, the clinical investigator may wish to submit an IDE and would, therefore, also act as the sponsor of the study. 

Federal law prohibits the distribution of medical devices until the FDA has reviewed clinical data and determined that a particular product is safe and effective for a specific use in human subjects. In order to test a new medical device in clinical trials, it is necessary to obtain an exemption from the FDA. Thus a device sponsor is required to apply for an Investigational Device Exemption (IDE) before tests with human subjects may begin. The investigator is responsible for obtaining the IDE number and providing it to the IRB. Studies that involve FDA-regulated products that are submitted without an IDE number will be reviewed by the IRB with respect to determining the need for an IDE, based on federal requirements and the investigator's response to questions contained in the protocol.

If the IRB determines that the study does not require an IDE and approves the study, the study may begin. If the IRB determines that an IDE is needed, the investigator/sponsor must submit an IDE application to the FDA and provide documentation of the outcome of the FDA determination (IDE number) to the IRB before the IRB gives approval to enroll subjects in the study.

When is an IDE from the FDA required?

  • Studies involving unapproved devices that are considered to be significant risk: An IDE from the FDA is required to perform clinical research using an unapproved device that poses a significant risk to subjects. Typically, these studies are conducted to collect safety and effectiveness data used to support Premarket Approval (PMA) applications submitted to the FDA.
  • Studies involving an approved device being tested for a new indication: IDE regulations also apply to significant risk studies testing an FDA-approved device for a new indication.

Example: Significant risk (SR) studies involve implantable devices such as cardiac pacemakers, orthopedic implants, and stents. SR studies can also involve products not introduced into the body, such as computer software used for prenatal risk evaluation. Each of these studies would require an IDE. For more information, see FDA guidance on Significant and Non-Significant Risk Medical Devices.

Example: A legally marketed coronary stent would be considered an investigational device and would require an IDE if used as part of a study to collect safety and effectiveness data for treating occlusions of other vascular sites.

When is an IDE from the FDA not required?

  • Studies involving devices that are considered to be non-significant risk (NSR): An IDE from the FDA is not needed for research when the sponsor provides a brief explanation of why the device is NSR and the IRB agrees with the sponsor’s explanation.

The following guidance includes examples of significant-risk devices and NSR devices: Significant and Non-significant Risk Medical Devices.

Process for obtaining an IDE

  • Pre-IDE Process: Investigators considering submitting an IDE application to the FDA should communicate with the reviewing division of the Office of Device Evaluation (ODE) prior to the submission of an IDE application. See the FDA IDE Approval Process website for details.
  • The IDE Submission: The IDE submission to the FDA and the IRB application should be initiated at the same time. The FDA has 30 days to review the IDE application. Likewise, the IRB typically reviews an application within a 30-day window, but it may take longer to secure approval. Subjects may not be recruited or enrolled before FDA and IRB approval.

IDE Letter and Detailed Description of the Device

For all investigational devices, you must submit detailed information about the device, similar to an Investigator’s Brochure.

For research involving a significant risk device, investigators must submit an IDE approval letter from the FDA with the application for initial review. If the sponsor has not yet received the approval letter, the IRB will review the study and may approve it with the condition that the study cannot start until the investigator submits a copy of the IDE approval letter to the IRB and the IRB acknowledges receipt.

Ethical Considerations

For investigations involving a medical device that is exempt from the requirement for an IDE, the IRB may approve the study without an IDE.

For research that is not exempt from the requirement for an IDE, the IRB will determine if the investigational device is a significant risk device based on the information in the application.

  • If the IRB agrees that the device is NSR, an IDE from the FDA will not be required.
  • If the IRB determines that the device poses a significant risk, then the study will be reviewed at the Full Committee level for future submissions.

Investigator Responsibilities for Investigational Devices

If an investigator is the developer of the drug, biologic or medical device, and no commercial manufacturer is involved, then the investigator is also the sponsor for the purposes of designing and organizing clinical trials.

Sponsors also have important administrative and reporting requirements above and beyond those of investigators. Faculty contemplating the dual role of sponsor-investigator should consult with the School of Medicine Clinical Trials Office (SOM CTO) about the additional responsibilities that entails.

The sponsor must declare any individual financial conflict(s) of interests in the research and develop a management plan that is approved by the University.

Should an investigator associated with the University of Virginia or the University sponsor a multi-site study, that investigator is required to meet all the responsibilities of a sponsor as determined by DHHS guidance.

At the time of initial review, the IRB will require an approval from the SOM CTO who will assess the procedures for dissemination of protocol information (e.g. unanticipated problems involving risks to subjects or others, protocol modifications, interim findings) to all participating sites. In addition, the UVA PI must ensure that investigators at other research sites submit and follow requirements directed by their local IRBs.

IRB policies and procedures from each approving institution will be followed by researchers at that site. All required reports will be provided to the local IRB as per their policy. The coordinating PI at the University of Virginia will be responsible for providing local information as well as unanticipated problems involving risks to subjects or others, protocol modifications, or interim findings that may affect the control of investigational devices.

Control of Investigational Devices

Investigators conducting studies in which an investigational device will be used must ensure adequate control of the device. Adequate control and handling of investigational devices include all of the following:

  • Ensuring that the investigational device is used only as described in the IRB approved protocol, the signed agreement, the investigational plan and applicable FDA regulations.
  • Providing the investigational device only to participants under the investigator’s direct supervision or under the supervision of a sub-investigator responsible to the investigator.
  • Supplying the investigational device only to persons authorized to receive the device.
  • Maintaining accurate, complete, and current records relating to the investigator’s participation in an investigation, including records of receipt, use or disposition of a device that relate to:
    • The type and quantity of the device, dates of its receipt, and the batch number or code mark.
    • The names of all persons who received, used, or disposed of each device.
    • Why and how many units of the device have been returned to the sponsor, repaired, or otherwise disposed of.
  • Returning any unused devices or following the sponsor’s requirements for disposition of unused devices if the investigation is terminated, suspended, discontinued, or completed. See Sample Investigational Device Accountability Log.

Importing Medical Devices

A complete overview of medical device import/export regulations is provided by the Center for Devices and Radiological Health (CDRH). Clinical investigators should be aware that the FDA does not recognize regulatory approvals from other countries. Therefore, an imported medical device must meet all FDA requirements.

  • The IDE sponsor must be located in the United States.
  • Anyone who intends to import an investigational device takes on the responsibilities of a sponsor.

Investigator Reporting Requirements

Drug-Device Combination Products

If an investigator is interested in investigating a combination product, the following links may be useful:

  • The FDA’s Office of Combination Products (OCP) was created in 2002 to facilitate the review process for combination products by coordinating interactions between reviewing branches.
  • The OCP provides applicable guidance documents for combination products.
  • Some recent combination product approvals include:
    • Drug-eluting coronary stents;
    • Spinal fusion putty; and
    • An influenza vaccine administered via an intranasal delivery device.

Device Classifications

The level of regulatory controls placed on a medical device is determined by the risk classification. Most research reviewed by the IRB involves significant risk, Class III devices. To help determine device classification, regulatory controls, and exemptions, the CDRH maintains:

  • A searchable classification database containing information about all approved Class I, Class II, and Class III devices.
  • A listing of Class I and Class II devices deemed exempt from Premarket Notification 510(k) regulations.

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 Nonsignificant 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. 

Exemption for Devices

If something is determined to be a device, one must 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.  A summary of the FDA regulations for studies exempt from the IDE regulation include: 

* Noninvasive when applied to a diagnostic device or procedure, means one that DOES NOT by design or intention: 

According to 21CFR812.2(c) (7) a custom device as defined in 812.3(b) is exempt unless the device is being used to determine safety or effectiveness for commercial distribution.  A custom device means a device that:

Depending upon the nature of the investigation, those studies which are exempt from the requirements of the IDE regulation may or may not be exempt from the requirements for IRB review and approval under Part 56and the requirements for obtaining informed consent under Part 50. For guidance regarding the applicability of these regulations with respect to investigations being conducted under the provisions of §812.2(c), contact the IDE Staff at (301) 594-1190.

For a custom device, IRB approval is required as this would also not meet the definition of human subject research under 45CFR46. 

  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. For additional information see the FDA Guidance on Mobile Medical Apps- 9-23 13

For more information see: Guidance on Electronic Storage of Highly Sensitive Data Policy

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.

o apps that use patient-specific parameters and calculate dosage or create a dosage plan for radiation therapy;

o Computer Aided Detection software (CAD);

o image processing software24; and 

o 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. 

o Body Mass Index (BMI)

o Total Body Water / Urea Volume of Distribution

o Mean arterial pressure

o Glascow Coma Scale score

o APGAR score

o NIH Stroke Scale

o Delivery date estimator

Expanded Access to Unapproved Medical Devices

The Food and Drug Administration's Expanded Access Program allows for medical devices that are investigational (i.e., not FDA approved) to be used for treatment use outside of a clinical trial. Such use is not considered a clinical investigation however, FDA submission AND IRB review are necessary. 

The criteria for Expanded Access are largely determined by (1) the seriousness of a patient's condition, (2) other available FDA-approved treatment options, (3) patient population size needing treatment, and (4) device status.

Unapproved medical device: is a device that is utilized for a purpose, condition, or use for which the device requires, but does not have, an approved application for premarket approval under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360e)(the act) or an approved IDE under section 520(g) of the act (21 U.S.C. 360j(g)).

IDE: An approved investigational device exemption permits a device that otherwise would be required to comply with a performance standard or to have premarket approval to be shipped lawfully for the purpose of conducting investigations of that device.

If enrollment in an existing clinical trial is not possible (e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials to address the patient’s condition), patients/physicians have the potential to receive expanded access to investigational devices under one of three alternative mechanisms.

Single Patient Emergency Use of an Unapproved Medical Device:

Note:  DO NOT USE CRCONNECT or Protocol Builder to create your templates.

 

The FDA defines "emergency use" as the use of a test article when:

  1. The patient has a life-threatening condition that needs IMMEDIATE treatment
  2. No generally acceptable alternative treatment for the condition exists; and
  3. Because of the immediate need to use the medical device, there is no time to use existing procedures to obtain FDA approval for the use obtain IRB approval [21 CFR 56or.102 (d)] [PDF].

Emergency use of an unapproved device may also occur when:

  1. An IDE for the device does not exist, or
  2. When a physician wants to use the device in a way not approved under the IDE, or
  3. When a physician is not an investigator under the IDE 

Life-threatening, for the purposes of section 56.102(d), includes the scope of both life-threatening and severely debilitating, as defined below.

  • Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the patients must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
  • Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

FDA expects the physician to make the determination that the patient’s circumstances meet the above criteria (1-3), to assess the potential for benefit from the use of the unapproved medical device and to have substantial reason to believe that benefits will exist.

If there is an IDE for the unapproved medical device, the IDE sponsor must notify the FDA of the emergency use within 5 days through submission of an IDE Report (§812.35(a)(2)).This follow-up report should include a summary of the conditions constituting the emergency, the patient protection measures that were followed, and patient outcome information.

If no IDE exists, the UVA physician should submit a follow-up report on the use of the device (description of device used, details of the case, and the patient protection measures that were followed) to:

Food and Drug Administration
Center for Devices and Radiological Health
10903 New Hampshire Ave Document Control Center WO66 Rm G-609 Silver Spring, MD 20993

Procedures for IRB submission for Single Patient Emergency use of an Unapproved Medical Device

Emergency Use does not need IRB or FDA approval before use. However, if there is time, the UVA IRB-HSR asks that, the IRB-HSR be notified in advance of the proposed emergency use of an unapproved medical device.  

FDA guidance indicates that BEFORE using an unapproved medical device, the physician should take as many of the following patient protection measures as possible, and provide the following information in the submission:

  • Obtain a written independent assessment of the use of the device by an uninvolved, independent physician
  • Obtain documented informed consent from the patient or patient’s legally authorized using the template: Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device
    • If consent cannot be obtained before use, please let the IRB-HSR know why this was the case in your correspondence. The UVA physician and an independent licensed physician who is not participating in the medical care of the patient must certify in writing that:
      • The patient has a life-threatening or serious disease or condition
      • There was an inability to communicate with or obtain legally effective informed consent from the patient
      • There was not sufficient time to obtain informed consent from the subject or legally authorized representative
      • There was no available alternative method of FDA-approved or generally recognized therapy that provided an equal or greater likelihood of saving the patient’s life.
  • Obtain documented authorization from the holder of the IDE/device manufacturer
  • Obtain clearance from UVA Clinical Engineering for use of the unapproved investigational medical device
  • Notify the UVA IRB with a written description of the circumstances necessitating the use of the device, along with documentation of the uninvolved physician’s assessment, informed consent, and the IDE holder’s authorization.

NOTE: In the event of a waiver of informed consent for an emergency use, the IRB Chair or Designated IRB member, will confirm that both the investigator and an independent physician who is not otherwise participating in the care of the patient, have certified in writing all of the following:

  • the patient is confronted by a life-threatening situation necessitating use of the test article;
  • informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the patient;
  • time is insufficient to obtain consent from the patient’s legally authorized representative;
  • no alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the patient’s life;

Prior FDA approval for shipment or use of the device is not necessary but emergency use needs to be reported to the FDA and IRB. The information to the FDA should be submitted by the sponsor (IDE holder). If the unapproved medical device is not under an IDE, the investigator should submit the information directly to the FDA.

Send the following documentation to the UVA IRB via sirb@virginia.edu Subject: Request for Single Patient Treatment Use of an Unapproved Medical Device 

Emergency use to the UVA IRB-HSR and the FDA must be reported within five working days.

Include the following documentation:

 

SINGLE PATIENT NON-EMERGNECY USE

Note:  DO NOT USE CRCONNECT or Protocol Builder to create your templates.

 

FDA approval and IRB Concurrence are required BEFORE the use of the device. The submissions to the FDA and the IRB -HSR can occur simultaneously, but both are needed before use.

FDA guidance indicates that BEFORE using an unapproved medical device, the physician should take as many of the following patient protection measures as possible, and provide the following information in the submission:

  • Obtain a written independent assessment of the use of the device by an uninvolved, independent physician
  • Obtain documented informed consent from the patient or patient’s legally authorized using the template:  Emergency Use or Expanded Access Consent for Investigational Drugs, Biologics or Device
    • If consent cannot be obtained before use, please let the IRB-HSR know why this was the case in your correspondence. The UVA physician and an independent licensed physician who is not participating in the medical care of the patient must certify in writing that:
      • The patient has a life-threatening or serious disease or condition
      • There was an inability to communicate with or obtain legally effective informed consent from the patient
      • There was not sufficient time to obtain informed consent from the subject or legally authorized representative
      • There was no available alternative method of FDA-approved or generally recognized therapy that provided an equal or greater likelihood of saving the patient’s life.
  • Obtain documented authorization from the holder of the IDE/device manufacturer
  • Obtain clearance from Clinical Engineering for use of the unapproved investigational medical device

Notify the UVA IRB with a written description of the circumstances necessitating the use of the device, along with documentation of the uninvolved physician’s assessment, informed consent, and the IDE holder’s authorization.

The physician who intends to use the device must determine that the following criteria are met:

  • The medical device is intended to treat or diagnose a serious disease or condition
  • There is no comparable or satisfactory alternative device or therapy available

Procedures for IRB submission for Single Patient Non-Emergency Treatment use of an Investigational Medical Device

Send the following documentation to the UVA IRB via sirb@virginia.edu Subject: Request for Single Patient Non-Emergency Treatment Use of an Unapproved Medical Device 

The sponsor of the IDE/device manufacturer is required to submit an IDE supplement requesting approval under 812.35(a) in order to treat the patient.  For further instructions about FDA requirements for the IDE supplement, please refer to the FDA website.

The physician may not treat the patient identified in the IDE supplement until FDA approves the treatment use for the intended patient.  FDA will consider preliminary evidence of safety and effectiveness as well as whether the compassionate use would interview with the conduct of a clinical trial to support marketing approval.  Once approved, the patient should be monitored for safety.   Follow up information on the use of the device should be submitted in an IDE Report after compassionate use has ended.

FOLLOW-UP:

After the use of the test article, you are required to notify the UVA IRB-HSR within 5 working days about the status of the patient using the Single Patient Treatment Follow-up form.  The FDA and sponsor will need a similar report. Be aware of the reporting requirements noted in the table that follows.

TREATMENT USE FOR UNAPPROVED MEDICAL DEVICES (intermediate or large groups)

These procedures are intended to facilitate that availability of devices that are not FDA approved for marketing but are under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom there is no comparable or satisfactory alternative device or treatment available.  During the trial or prior to final FDA action on the marketing approval, it may be appropriate to use the device to treat patients not in the trial under treatment IDE regulations (21 CFR 812.36).
For the purposes of treatment use, immediately life-threatening disease means a stage of a disease in which there is reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.

The physician who intends to use the device must determine that the following criteria are met:

  • The device is intended to treat or diagnose a serious or immediately life-threatening disease or condition;
  • There is no comparable or satisfactory alternative device or other therapy available to treat or diagnose that stage of the disease or condition in the intended patient population;
  • The device is under investigation in a controlled clinical trial for the same use under an approved IDE, or such clinical trials have been completed; and
  • The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence.
Procedures for IRB submission of protocols for treatment use of unapproved devices
For investigator-initiated IDEs, compassionate use protocols must be submitted per usual procedures through CRCONNECT and the UVA IRB-HSR and requires full IRB review and approval under FDA regulations.  Please see the School of Medicine website for information about preparing an IDE submission to FDA.

 

CONTINUED ACCESS (EXTENDED INVESTIGATION) OF AN UNAPPROVED MEDICAL DEVICE

FDA may allow continued enrollment of subjects after the clinical trial under an IDE has been completed to allow access to the investigational medical device while the marketing application is being prepared by the sponsor or reviewed by FDA.  This is known as an “extended investigation”. A sponsor’s request for an extended investigation should be submitted as an IDE supplement. 

The physician who intends to use the device must determine that the following criteria are met:

  • Public health need for the device, OR
  • Preliminary evidence that the device will be effective and there are no significant safety concerns
 
Procedures for IRB submission of protocols for continued access to unapproved devices

For investigator-initiated IDE supplements for an extended investigation, continued access protocols must be submitted per usual procedures through CRCONNECT and the UVA IRB-HSR and requires full IRB review and approval under FDA regulations.  Please see the School of Medicine website for information about preparing an IDE submission to FDA.

HUMANITARIAN USE DEVICE

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 not more than 8,000 individuals in the United States per year.  FDA regulations (21 CFR 814.124) provide for the submission of a Humanitarian Device Exemption (HDE) in which the manufacturer is not required to provide the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose prior to marketing. This regulation was developed to provide an incentive for the development of devices for use in the treatment or diagnosis of diseases affecting these populations.

An HDE is a type of Pre-Market Approval (PMA) that allows the FDA to grant an exemption from the effectiveness requirements of the PMA regulations. Devices approved with an HDE are referred to as a Humanitarian Use Devices (HUD). The provisions for obtaining an HDE are:

  • The device is designed to treat or diagnose a disease or condition that affects fewer than 8,000 individuals per year in the U.S.
  • The device is not available otherwise, and there is no comparable device available to treat or diagnose the disease or condition; and
  • The device will not expose patients to unreasonable or significant risk, and the benefits to health from the use outweigh the risks.

Treatment under an HDE is not considered research, but the FDA requires IRB approval prior to use. The IRB looks at the safety of the device and decides what information patients should receive about the safety and effectiveness of the HUD. Physicians who want to use a HUD at UVA should submit a standard IRB application through CRCONNECT and Protocol builder.

When the manufacturer submits the HDE it must provide sufficient information in order for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury to the patient and that the probable benefits to health outweigh the risk of injury or illness from its use.

A Humanitarian Device Exemption (HDE) application is similar to a premarket approval (PMA) application. However, due to the limited size of the target population and the impracticability of conducting clincal trials to establish safety and effectiveness, an HDE is exempt from the requirement to establish reasonable assurance of effectiveness. The FDA's approval is based its determination that the device will not expose patients to an unreasonable risk of injury or illness and the "probable benefit" to health. This is a considerably lower standard than proof of safety and effectiveness.

FDA approval of an HDE authorizes an applicant to market the HUD, subject to certain profit and use restrictions. HUDs cannot be sold for profit, except in very limited circumstances. Most importantly, they can only be used in a facility after an IRB has approved their use in that facility, except in certain emergencies.

How is an HDE different from an IDE?

An IDE is an exemption that allows a sponsor to ship an investigational device prior to marketing approval; it authorizes the investigational use of the device. A HUD with an approved HDE is approved for marketing. This means that the sponsor can ship the device and can bill for its use (but cannot make a profit from its sale except under limited circumstances). To receive approval for an HDE, the FDA must conclude that there is no comparable device available to treat the disease or condition. If a comparable device is approved by the FDA, the HDE approval may be withdrawn. An HDE therefore is analogous to a PMA application; it’s an application to market the device. An IDE is an application to ship an investigational device to conduct studies.

To approve a PMA device, the sponsor has to provide data from adequate and well-controlled trials that provide substantial evidence of effectiveness (and safety). The requirements for approval of an HDE application to market a HUD are quite a bit lower. FDA's Q&A states that an approved HDE represents "a determination by FDA that the HUD will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from use of the device outweighs the risk of injury or illness from its use while taking into account the probable risks and benefits of currently available devices or alternative forms of treatment."

What are the IRB's Responsibilities for a HUD?

Before a HUD under an approved HDE can be used at the University of Virginia or its affiliates for clinical care, approval by an IRB is required, with the exception of emergency use. A HUD is the only situation where federal regulations require the IRB to approve and monitor an activity that is clearly not research. The IRB review of HUDs can be particularly challenging, given that there is no research objective or design, no investigational device, no subjects, no study harm, or benefits. The primary reason for this requirement may be to give notice to the institution that the HUD will be used. It should be noted that the IRB’s approval for the use of a HUD at a facility to treat or diagnose patients in the course of providing clinical care does not mean that there is IRB approval of a clinical investigation involving the HUD.

After HDE approval, a HUD may only be used after IRB-HSR Full Board approval has been obtained for the use of the device, even for the FDA-approved indication, except for an emergency use situation. The IRB is required to perform its initial review at a convened meeting using the criteria for approval at 21 CFR 56.111. Subsequent continuing reviews - at least annually - may be performed using expedited procedures. Expedited review is permitted because a HUD is an approved device.

The IRB may approve the device for either

  • General use; or
  • For groups of HUD patients that meet certain criteria;.
  • For patients under a HUD protocol; or
  • On a case-by-case basis.

 

Physician Responsibilities for the Use of a HUD

Note:  DO NOT USE CRCONNECT or Protocol Builder to create your templates.

A physician may utilize a HUD when agreeing to the following:

  • The HUD will be utilized for treatment, diagnosis, or research in accordance with the labeling of the device, intended purpose, and in the designated population for which the FDA approved its use;
  • The patient must be informed that the HUD is a device authorized under Federal law for use; however, the effectiveness of the device for a specific indication has not been demonstrated; and
  • The informed consent of the patient or the patient’s legally authorized representative will be obtained when the use of the HUD involves research or when required by the IRB. The IRB generally requires that treating physicians obtain informed consent. A HUD Informed Consent form template has been developed for your use.

IRB Submission Requirements for Use of a HUD

Regardless of the intended use, a HUD requires prospective IRB review and approval by the full board, with the exception of Emergency Use of an HDE. For an Emergency HDE, refer to process outlined earlier for ”Single Patient Emergency Use of an Unapproved Medical Device”:

Send the following documentation to the UVA IRB via sirb@virginia.edu Subject: HUD Request

Continuing Review Requirements for HUD

The physician is responsible for fulfilling continuing review requirements to the IRB at least annually. At the time of continuing review, the physician must report the HUD activities for the previous 6 months from UVA. In addition, the following information must be provided to the IRB in summary form for each HUD at UVA. This report must include the following:

  • The clinical indications for the use of the HUD in each patient;
  • Clinical outcomes of each participant, if known.

Modifications to the HUD

Modifications to the HUD or the clinical use of the HUD are to be promptly reported to the UVA IRB in accordance with the IRB policy for Modifications at UVA.

Emergency Use of a HUD

Off-label use of a HUD in an emergency situation that cannot wait for IRB review and approval may be handled under Single Patient Emergency Use of an Unapproved Medical Device provision provided that the situation meets the FDA criteria under 21 CFR 56.104 (d) and the HUD is not used outside its approved labeling.

Required Approval Process to Use a New Device at UVA Health System

No medical device (supplies, accessories, or equipment), whether purchased, contracted, donated, loaned or for trial, may be used in the Medical Center for inpatient or outpatient care purposes without first being evaluated by Clinical Engineering. 

The Food and Drug Administration (FDA) defines a medical device as any instrument, apparatus, or other article that is used to prevent, diagnose, mitigate, or treat a disease or to affect the structure or function of the body, with the exception of drugs. This means that the FDA classifies common hospital products such as catheters, thermometers, patient restraints and syringes as medical devices.

In order to obtain approval submit the New Medical Device Request Form online at https://www.healthsystem.virginia.edu/newmedicaldevice/index.cfm?requestid=new

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