Expanded Access for Medical Devices, Drugs, and Biologics in a Non-Emergency Situation (Compassionate Use)

Expanded Access is a Food and Drug Administration (FDA) pathway that allows physicians to use an investigational device, drug, or biologic to treat or diagnose an individual patient or a small group of patients when they have a serious medical condition and there are no available alternative options, including participation in a clinical trial. There are three mechanisms for expanded access (Compassionate Use, Emergency Use, and Treatment Use); this guide ONLY covers Compassionate Use.

The guidance below addresses all of the following: 

Physicians seeking access to investigational or unapproved drugs, biologics, or devices under the Compassionate Use provision must follow the guidance below as applicable

Compassionate Use Criteria 

To use the Compassionate Use pathway, all of the following criteria must be met:

  • The patient has a serious disease or condition, or their life is immediately threatened by the disease or condition.
  • There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
  • Patient enrollment in a clinical trial is not possible.
  • The expected benefits to the patient outweigh the risks of the treatment.
  • Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.
     

Medical Device, Drug, or Biologic Company/Manufacturer Approval

The drug, biologic, or medical device company must agree to make the investigational product available for the proposed Compassionate Use.

FDA Approval

Devices

When there is an IDE for the device:The IDE sponsor submits an IDE amendment requesting approval for the Compassionate Use under 21 CFR 812.35(a).
When there is no IDE for the device: 
  • The physician or manufacturer submits the following information to the FDA:
    • Cover Letter with: Physician's qualifications, treatment plan, monitoring and safety reporting plan, IRB contact information
    • A description of the device (provided by the manufacturer)
    • Authorization from the device manufacturer for the use
    • Letter of authorization (LOA) 
    • A description of the patient’s condition and the circumstances necessitating treatment or diagnostics
    • A discussion of why alternative therapies/diagnostics are unsatisfactory
    • Confirmation that the expanded access will not interfere with clinical trials or device development
    • Patient protection measures, including: 
      • Draft informed consent document
      • Clearance from the institution (at UCSF, this means approval from their departmental/divisional leadership and the relevant clinical practice space management where the procedure is intended to be performed (e.g., OR, Ambulatory Surgery, Catheter lab, etc.))
      • Concurrence of the IRB Chair or Chair-designated IRB member
      • Independent assessment from an uninvolved physician

Need assistance submitting? Contact CDHR at [email protected] for assistance.

Drugs and Biologics

When there is an IND for the drug or biologic:The IND sponsor submits an IND amendment requesting expanded access for the patient or group of patients under 21 CFR 312.310 (single patient) or 312.315 (intermediate-size).
When no IND exists:
  • The physician or manufacturer generally submits a new Expanded Access IND (EA-IND) to the FDA. Required documents include:
    • FDA Form 3926 (for single-patient expanded access) or FDA Form 1571 + protocol (for intermediate-size INDs)
      • Check question 10.b. on the FDA Form 3926 to request authorization to use alternative IRB procedure to allow the IRB Chair to review.
    • A description of the investigational drug or biologic
    •  Approval/Authorization from the manufacturer
    • Letter of authorization (LOA) from the manufacturer allowing FDA to reference the company’s IND or Drug Master File (DMF), if applicable
    • A clinical description of the patient’s condition and justification for the request
    • Patient protection measures, including:
      • Informed consent documentation
      • IRB review and approval
      • Independent assessment from an uninvolved physician
      • Safety reporting plan

Questions about submitting? Find the appropriate FDA contact. 

UCSF IRB Approval
 

To obtain the concurrence of the IRB Chair, follow these steps:

  1. Submit Individual Patient, Small Group, and Intermediate Size Compassionate Use requests via UCSF’s IRB submission system.
  2. Include “Individual Patient Compassionate Use” or “Small Group Compassionate Use” in the title of the IRB submission.
  3. Attach required documents, including:
    • FDA Form 3926 or FDA Form 1571
    • FDA Approval Letter
    • Informed Consent Form using the Expanded Access Consent Form Template
    • HIPAA Authorization Form
    • Investigator’s Brochure or device manual
    • Manufacturer Permission
    • Physician Letter
    • Second Physician Opinion Letter
    • Radiation Safety Committee approval (if applicable)
  4. Remove all 18 HIPAA identifiers from attached documents.
     

Principal Investigator (PI) Responsibilities

FDA and IRB Follow-Up:

Submit a follow-up report to both the FDA and the IRB within 45 days summarizing the patient’s clinical course, adverse events, and outcomes

Safety Monitoring and Adverse Event Reporting:

The PI must monitor the patient for adverse events. Adverse events must be reported to the IND sponsor if the IND sponsor is not the PI of the study. Serious and unexpected suspected adverse reactions (SUSARs) must be reported to the FDA by the IND sponsor. Adverse events must also be reported to UCSF IRB in accordance with IRB policy.

Recordkeeping:

Maintain accurate case histories, including clinical records and documentation of device disposition.

Reporting:

Submit required safety reports, amendments, and annual reviews to the FDA and IRB. Note: annual reporting is required when the compassionate use is active for ongoing treatment or monitoring.

Frequently Asked Questions

Do single patient Compassionate Use requests require full board review?

No. IRB Chair review is appropriate for individual patient requests.

Do I need additional permission beyond the IRB?

Check with departmental/divisional leadership and clinical practice space management.

Do I need to report adverse events to the IRB?

Yes, follow normal adverse event reporting guidance.

 

Resources

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