Expanded Access | Information for Institutional Review Boards (IRBs)

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On this page, you will find information about:

• What is expanded access?
• Keywords, definitions, and resources
• What are the roles and responsibilities?
• Are expanded access submissions subject to the informed consent requirements?
• Is IRB review and approval required for all expanded access categories? 
  • What is required for expanded access?
  • How can a physician submit a request for a waiver of the full IRB review requirement? 
  • If the initial review of an individual patient expanded access IND was done through concurrence by the full IRB, can the physician request subsequent review be done by either the IRB chair or their designee? 
  • What is required in emergency situations?
  • Are waivers of the requirement for full IRB review and approval appropriate for intermediate and treatment INDs/protocols?
• What factors should IRBs consider when reviewing Individual Patient Expanded Access Requests?
• How can an IRB report concerns to FDA?
• Additional resources

Learn About Keywords, Definitions, and Resources

What is expanded access?

Sometimes called “compassionate use”, expanded access is a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

When seeking expanded access to an investigational medical product, it is critical that the patient and his/her licensed physician consider all possible risks. Investigational medical products have not yet been approved or cleared by FDA and FDA has not found these products to be safe and effective for their specific use. Furthermore, the investigational medical product may, or may not, be effective in the treatment of the condition, and use of the product may cause unexpected serious side effects.

Whenever possible, an investigational medical product should be used as part of a clinical trial. However, if patient enrollment is not possible (e.g., patient ineligibility, lack of ongoing clinical trials) or enrollment in a clinical trial is not feasible (e.g., distance to a trial precludes access), expanded access offers a possible route for gaining access to an investigational medical product.

FDA is committed to increasing awareness about its expanded access process and the procedures for obtaining access to investigational drugs, biologics, and medical devices.

Learn more about expanded access categories for drugs and biologics.

Learn more about expanded access categories for medical devices.

What are the roles and responsibilities?

1. Patient
   Consults with licensed physician to explore and decide about alternative options.
2. Licensed Physician
   Agrees to oversee the patient's treatment and works with industry (e.g., medical product developer), files paperwork with FDA and IRB (for many expanded access request types), and is responsible for patient care and reporting.
3. Company (Industry)
   Willing to provide the investigational medical product and either submits the expanded access request to FDA, allows the FDA to cross-reference their IND (for drugs and biologics) or IDE (medical devices) on behalf of the expanded access sponsor-investigator through the use of a letter of authorization, or provides the necessary investigational medical product information for the sponsor-investigator to submit to support an expanded access request.
4. Institutional Review Board (IRB)
   Reviews expanded access protocol and consent to ensure that the patient is informed about the nature of the treatment.
5. FDA
   Reviews the expanded access request and determines if the treatment may proceed.

Are expanded access submissions subject to the informed consent requirements?

FDA’s informed consent requirements apply to clinical investigations as described in 21 CFR 50.1(a). One of the purposes of informed consent is to ensure patients understand they may be treated with an investigational product and there may be uncertainty about the safety and effectiveness of the product. The term clinical investigation is defined in 21 CFR 50.3(c) to include “any experiment that involves a test article and one or more human subjects and that is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act. . . .”

FDA considers expanded access use of an investigational medical product to meet the definition of clinical investigation in § 50.3(c). Therefore, expanded access to an investigational medical product for treatment use, including emergency use, requires informed consent as described in 21 CFR part 50, unless one of the exceptions found in part 50 applies. Investigators treating a patient or patients with an investigational medical product under expanded access are responsible for ensuring the informed consent requirements of part 50 are met (21 CFR 312.305(c)(4)).

See FDA’s draft guidance: Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers.

FDA has shared an informed consent template investigators may find helpful for obtaining informed consent from patients for individual patient expanded access.

For more information about expanded access for medical devices, please see: Expanded Access for Medical Devices.

Is IRB review and approval required for all expanded access categories?

What is required for expanded access?

Drugs and biologics: 

• Except for emergency expanded access use when there is not sufficient time to secure prospective IRB review, an investigator treating a patient with an investigational drug under expanded access is responsible for ensuring that IRB review is obtained consistent with 21 CFR part 56 before treatment with the investigational drug may begin, regardless of whether the protocol is submitted in a new investigational new drug (IND) or to an existing IND (21 CFR 312.305(c)(4)). Part 56 requires, among other things, that the IRB review the expanded access use at a convened IRB meeting at which a majority of the members are present (full IRB review) (21 CFR 56.108(c)).

Process for medical devices: 

• For medical devices, only IRB chair concurrence is required. 

How can a physician submit a request for a waiver of the full IRB review requirement? 

Drugs and Biologics:

• For individual patient expanded access INDs where the IRB chairperson or another designated IRB member provides concurrence before treatment use begins, the review would follow a different review pathway that is neither full board nor expedited, but rather one in which the IRB chair or designee reviews the relevant documents (as determined by the IRB).  The decision to concur or not (and/or any questions and responses) is documented by the IRB chair or designee. FDA concludes that such a waiver is appropriate for individual patient expanded access INDs for the initial submission, any amendments (e.g., for change in the use or duration of treatment) to the IND, and, if applicable, continuing review. FDA intends to consider a completed Form FDA 3926 with the box in Field 10.b selected and the form signed by the physician to be a request for a waiver under 21 CFR 56.105 of the requirements in § 56.108(c), which relates to full IRB review. When a waiver is requested in this manner, the physician does not receive notice from FDA indicating that the waiver is granted. Alternatively, the physician may request a waiver separately in an amendment to the IND. When the request for waiver is accomplished by submission of a separate waiver request, FDA issues a response to the waiver request.

If the initial review of an individual patient expanded access IND was done through concurrence by the full IRB, can the physician request subsequent review be done by either the IRB chair or their designee? 

Drugs and Biologics:

• If the initial protocol under an individual patient expanded access IND was reviewed and approved by the full IRB but the physician would like any amendments or the continuing review to be conducted by the IRB chairperson or the chairperson’s designee instead, the physician may amend the IND with a correspondence that clearly indicates the intent of the amendment (to change the approach for continuing IRB review of the expanded access protocol) and that includes a request for waiver under § 56.105 of the requirements in § 56.108(c). As described previously, FDA intends to consider a completed Form FDA 3926 with the box in Field 10.b selected and the form signed by the physician to be a request for such a waiver. Alternatively, the physician may amend the IND with a separate request for waiver of continuing IRB review by the full IRB if Form 3926 is not used or if Field 10.b was not checked. Please see: How to Submit a Request (Forms).

Process for medical devices: Expanded Access for Medical Devices.

What is required in emergency situations?

Drugs and Biologics:

• Emergency individual patient expanded access IND: FDA authorization is required before initiation of treatment (21 CFR 312.310(d)). However, emergency expanded access use is exempted from obtaining full IRB approval before initiation of treatment (21 CFR 56.104(c)) provided that the IRB is notified of the emergency expanded access use within 5 working days of emergency use. Please see: How to Submit an Emergency Use Individual Patient IND and Step-by-step instructions.
  
  Following receipt of notification of such emergency use, the IRB should follow its documented standard operating procedure for review of emergency expanded access use. A physician may choose to use Form FDA 3926 for submitting the emergency expanded access application. In such emergency expanded access cases, the box in Field 10.b on Form FDA 3926 should be left unchecked because Field 10.b is intended for requesting a waiver to obtain concurrence by the IRB chairperson or by a designated IRB member, in lieu of full IRB review, before the treatment use begins for non-emergency individual patient expanded access. See FDA guidance: Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers.  

Process for medical devices: Expanded Access for Medical Devices.

Are waivers of the requirement for full IRB review and approval appropriate for intermediate and treatment INDs/protocols?

Drugs and Biologics:

• Intermediate IND/Protocol and Treatment IND/Protocol: The Agency believes a waiver is not appropriate for intermediate and treatment INDs and protocols. Section 312.23(a)(1)(iv) requires sponsor commitment that an IRB will be responsible for the initial and continuing review of the studies under an IND.
  
  See FDA guidance: Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers for more information. 

Process for medical devices: Expanded Access for Medical Devices.

What factors should IRBs consider when reviewing Individual Patient Expanded Access Requests?

FDA recommends that IRBs:

• Consider establishing procedures for a single IRB member to review an expanded access submission for an individual patient if the physician requests a waiver from the requirements for review by the full IRB.  These procedures should reflect the information that the IRB deems relevant for a single IRB member review and should include procedures designed to ensure that the member documents the decision to concur or not concur with the treatment. For medical devices, the single IRB member is the IRB Chairperson.
• Focus the review of an expanded access request for an individual patient on assessing the risks and benefits for the patient involved. The information reviewed by the IRB must be adequate to assess whether risks to the patient have been minimized and that such risks are reasonable in relation to anticipated benefits. FDA regulations under 21 CFR 56.111 outline the criteria for IRB review of research. In the context of an individual patient expanded access request, FDA does not expect that a protocol will be necessary to provide the IRB with sufficient information to determine if those criteria are satisfied. A thorough patient history and treatment plan, included in the Form FDA 3926 (for drugs and biologics) or in another document, can be sufficient to provide the information necessary for an IRB assessment. Such information should include:
  • The proposed treatment plan (e.g., daily dose, route, and frequency of administration of drug or procedures to be followed for device use, duration of planned treatment, criteria for discontinuation of treatment, and planned modifications for adverse events);
  • The planned monitoring for adverse events, response to treatment, and changes in clinical status, as well as proposed modifications to the treatment plan to mitigate risks to patients if appropriate;
  • The key details of the patient’s history, including diagnosis and summary of prior therapy (including response to such therapy), as well as information regarding a patient’s relevant clinical characteristics (such as comorbid conditions and concomitant medications) that are necessary to assess the potential for increased risks of the medical product;
  • Description of why alternative therapies are unsatisfactory and why the probable risk of using the investigational product is no greater than the probable risk from the disease or condition,
  • A summary of known risks of the medical product.

The following are also important components of an IRB’s review of an expanded access request for an individual patient:

• Assess the qualifications of the physician submitting the individual patient expanded access request.
• When the request is for a pediatric patient, confirm that adequate provisions are included for soliciting age-appropriate assent from children and permission from a parent or guardian, as required under 21 CFR 50.55.
• Confirm that the informed consent document contains the information required under 21 CFR 50.25.

See FDA guidance: Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products | FDA, III. Recommendations on IRB Procedures and Factors to Consider for Individual Patient Expanded Access Requests, for more information.

Process for medical devices: Expanded Access for Medical Devices.

How can an IRB report concerns to FDA?

Under 21 CFR 56.113, an IRB shall have the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB`s action and shall be reported promptly to the investigator, appropriate institutional officials, and the Food and Drug Administration.

See: Mandatory IRB Reporting: FDA Contacts | FDA

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Additional Resources

Guidance Documents

• Guidance for Institutional Review Boards and Clinical Investigators: Institutional Review Boards Frequently Asked Questions
• Guidance for Institutional Review Boards and Clinical Investigators: Non-local IRB Review
• Guidance for Institutional Review Boards and Clinical Investigators: Cooperative Research

Learning Resources

• Good Clinical Practice (GCP) Inquiries - in the column for “Category” there are several options that start with “IRB” - checking those boxes provides a view of all IRB-related questions answered by GCP in the past.
• Physician Resources for Seeking IRB Approval – Reagan-Udall Foundation’s Expanded Access Navigator

How to Locate an Available IRB

• A federal online database of IRBs can be accessed here, then click on the link for “advanced search” to search for an IRB by city/state.
• For  information about non-local IRB review: Guidance for Institutional Review Boards and Clinical Investigators: Non-local IRB Review
• FDA Final Guidance for IRBs, Clinical Investigators, and Sponsors: Informed Consent