Expanded Access

Expanded Access to Investigational Devices

Expanded Access to Investigational Drugs

Expanded Access to Investigational Devices (also referred to as "Compassionate Use")

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. Sometimes this is referred to as compassionate use. Such use is not considered a clinical investigation; however, FDA submission and IRB review are still 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.

This webpage is a summarized guide to the FDA regulations on Expanded Access to Investigational Devices for Treatment Use, found in FDA guidance on Expanded Access for Medical Devices. It does not provide full guidance for Expanded Access to Investigational Devices; as such, FDA regulatory materials must also be consulted for full information.

The following mechanisms may be employed to use unapproved medical devices:

• Emergency Use
• Compassionate Use
• Treatment Investigational Device Exemption
• Continued Access to Investigational Devices

Emergency Use of an Unapproved Device

The FDA defines "emergency use" as the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval [21 CFR 56.102(d)].

For more information about emergency use and for instructions on submitting an emergency use application, please see the IRB guidance, Emergency Use of a Test Article.

Compassionate Use of an Unapproved Device

The FDA defines "compassionate use" as the use of a test article on a human subject with a serious disease or condition for which there is no acceptable treatment available. FDA and IRB approval for compassionate use is required. The IRB will not approve an application for compassionate use until it has been approved by the FDA.

Compassionate use may only be employed during the clinical trial for which the device is being tested. Compassionate use approval may be given for an individual patient or a small group of patients.

Treatment Investigational Device Exemption

A device that is not approved for marketing may be under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available. During the clinical trial or prior to final action on the marketing application, it may be appropriate to use the device in the treatment of patients not in the trial under the provisions of a treatment investigations device exemption [21 CFR 812.36].

The FDA will consider approval of an investigational device under a treatment of IDE if the following criteria are met:

1. The device is intended to treat or diagnose a serious or immediately life- threatening disease or condition;
2. 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;
3. 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
4. The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence.

IRB approval of a treatment use IDE is also required before use may begin. The IRB will not approve an application for a treatment IDE until it has been approved by the FDA.

Expanded Access/Compassionate Use of an Unapproved Device

The FDA will consider allowing an investigational device may be made available during the preparation or review of a marketing application if the following criteria are met;

1. There is a public health need for the device, and
2. There is preliminary evidence that the device is likely to be effective and not significant safety concerns have been identified for the proposed indication.

For additional information regarding continued access, please see the FDA guidance, Continued Access to Investigational Devices During PMA Preparation and Review

IRB approval of continued access to an investigational device is also required before use may begin. The IRB will not approve an application for continued access until it has been approved by the FDA.

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Expanded Access to Investigational Drugs (also referred to as “Compassionate Use")

The Food and Drug Administration's Expanded Access Program allows for drugs that are investigational (i.e., not FDA approved) to be used for treatment use outside of a clinical trial. Sometimes this is referred to as compassionate use. Treatment 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) drug status.

This webpage is a summarized guide to the FDA regulations on Expanded Access to Investigational Drugs for Treatment Use, found in [21 CFR 312.300]. It does not provide full guidance for Expanded Access to Investigational Drugs; as such, FDA regulatory materials must also be consulted for full information.

Evaluating and Securing Expanded Access to an Investigational Drug

Step 1: Evaluate the seriousness of the patient's or patient's condition using the FDA's criteria.

All of the following criteria must be met, as described in 21 CFR 312.305(a):

1. The patient or patients to be treated have a serious or immediately life- threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition;
2. The potential patient benefit justifies the potential risks of the treatment use and those potential risks are not unreasonable in the context of the disease or condition to be treated; and
3. Providing the investigational drug for the requested use will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use.

Step 2: Determine the patient population size that requires treatment use and evaluate the drug status using the FDA's criteria.

Single Patient Emergency Use

• Definition: 21 CFR 56.102 (d); the patient is in an immediately life-threatening situation
• Criteria: 21 CFR 312.310 (a)
• Drug status: The patient cannot obtain the drug under another IND or protocol ( 21 CFR 312.310 (a)). 
  

Single Patient Non-Emergency Use

• Definition: [21 CFR 312.310 (a)]; the patient has a serious condition and is not in an immediately life-threatening situation
• Criteria: [21 CFR 312.310(a)]; the physician must determine that the probable risk to the person from the investigational drug is not greater than the probable risk from the disease or condition
• Drug status: The patient cannot obtain the drug under another IND or protocol  [21 CFR 312.310 (a)].

Intermediate-Size Patient Population

• Definition: [21 CFR 312.315]; the investigational use of a drug for the treatment of a patient population smaller than that typical of a treatment IND or treatment protocol
• Criteria: [21 CFR 312.315(b)]
• Drug status: [21 CFR 312.315(a)]

Large Patient Population, i.e. Treatment IND or Treatment Protocol

• Criteria and drug status: [ 21 CFR 312.320(a)]

Step 3: Determine if the Expanded Access requires a new IND or can be amended to an existing IND

An IND is required for all Expanded Access. An individual physician may apply to the FDA for an IND or may function under an existing IND held by another physician or the drug manufacturer. Some IND holders will not allow for Expanded Access to be amended to their existing IND; in this case, the physician must apply for a new IND. Consult with the IND holder to determine if an existing IND can be amended.

Step 4: Submit an Expanded Access submission to the FDA

Use the instructions provided in on FDA's webpage for the Expanded Access submission. These instructions must be followed for both new IND submissions and amendment submissions to existing INDs.

Step 5: Submit an application for IRB Review

For single patient emergency use, follow the Emergency Use of a Test Article instructions.

For all other expanded access options, submit a full new study application to the IRB. The application must include the following:

1. IND documentation from the FDA/drug manufacturer
2. Drug information via an Investigator's Brochure or a package insert
3. An informed consent document

In non-emergency situations, treatment may not begin until the IRB has approved the Expanded Access protocol.

Step 6: After initiating the treatment, ensure that all case histories and adverse events are properly recorded and reported.

[21 CFR 312.300] describes the safeguards and records that must be in place to ensure appropriate monitoring of patient safety. The requirements are different for the type of Expanded Access approved, based on patient population size. Ensure you are familiar with these requirements and can maintain appropriate records and oversight for Expanded Access protocols.