Emergency Use

FDA Resources for Expanded Access and Emergency Use

FDA 24/7 Contact Information:

The FDA mans a hotline 24 hours a day, 7 days a week for emergency requests. Click on the links for the FDA contact information.

• Physician Request for an Individual Patient IND under Expanded Access for Non-emergency or Emergency Use or
• FDA's Expanded Access Contact Information.

Guidance and Forms for Expanded Access to Investigational Drugs for Treatment Use

• FDA's Guidance - Expanded Access to Investigational Drugs for Treatment Use - Questions and Answers covers issues related to the treatment use of investigational drugs for a single individual, as well as intermediate and large size trials.
• Form FDA 3926 – Individual Patient Expanded Access Investigational New Drug Application (IND)
• Instructions for Filling Out Form 3926: Individual Patient Expanded Access IND

FDA Websites with Educational Materials about Expanded Access to Drugs and Devices:

• FDA page for Physician Request for an Individual Patient IND under Expanded Access for Non-emergency or Emergency Use.
• FDA page with educational information regarding IDE Early/Expanded Access.

Single Subject IND: Emergency Use of a Drug or Biologic

General Requirements:
The requirements for emergency use of a drug are included in the new (2009) 21 CFR 312 Subpart I: Expanded Access to Investigational Drugs for Treatment Use. Expanded Access includes single patient use, intermediate-size population use, and treatment use or treatment INDs. The requirements for all three types of expanded access in 21 CFR 312.305.

Specific Requirements for Single Patient IND:
The detailed requirements for a single patient use, including emergency use, can be found in 21 CFR 312.310.

IRB Requirements:
For drugs and biologics, the FDA regulations do not provide for expedited IRB approval in emergency situations. The FDA therefore, does not accept any of the following, though commonly used terms - "interim," "compassionate," or "temporary". There are three possible ways to proceed:

• the IRB can provide concurrence by the chair or another IRB member for the emergency use (see above), provided the FDA has granted a waiver under § 56.105 of the requirements in § 56.108(c), which relate to IRB review by the convened board;

• the IRB must convene and give full board approval for the emergency use (e.g. if the sponsor is a pharmaceutical company and not a physician sponsor-investigator, or the FDA has concluded that a waiver of the requirement for review and approval by a convened board is not appropriate); or,

• if the conditions of 21 CFR 56.102(d) are met (see information box to the right) and it is not possible to convene a quorum/chair concurrence within the time available, the use may proceed without any IRB approval/chair concurrence. This latter option is also known as an Emergency Exemption from prospective IRB review.

Subsequent Uses of an Investigational Drug or Biologic

The Emergency Exemption is for a single patient use. If the investigator anticipates the need to use the same drug for a second individual, then they must prepare a protocol for IRB approval for the proposed use.

Emergency Use of an Investigation Drug or Biologic - Information Sheet:

Emergency Exemption from Prospective IRB Review: Drugs and Biologics

Immediate life-threatening situations typically occur with short notice although occasionally the planned use can be foreseen 3 or 4 weeks in advance. When there is sufficient time, the IRB must review the proposed single patient use. When there is insufficient time for IRB review, the Investigator may exercise the Emergency Exemption from prior IRB review and administer the investigational drug.

Investigator Responsibilities When Exercising the Emergency Exemption

Contact the Manufacturer:
The investigator must obtain the manufacturer's agreement to ship the drug or to use part of the drug supply available at CHOP as part of another clinical trial.

Contact the FDA:
Either the investigator or the sponsor-IND holder must obtain an IND from the FDA for the emergency use. The FDA maintains 24 hour coverage for emergency INDs (see above).

Contact the IRB:
When there is sufficient time, the investigator should contact the IRB as soon as possible to determine whether or not the IRB can issue concurrence or convene and approve the emergency use. When there is insufficient time, the investigator may exercise the Emergency Exemption from prospective IRB review and must follow the procedures outlined in IRB SOP 802.

Notify the Pharmacy:
The investigator should provide the pharmacy with the following:

• a copy of the FDA's letter or email indicating its approval for the Emergency IND; the manufacturer's approval to ship drug;
• either evidence of IRB approval/concurrence or notice that the investigator is exercising the Emergency Exemption.

The drug must be shipped to the Pharmacy to maintain the appropriate chain of custody. The Pharmacy will not accept medications shipped to the investigator without proper shipping and storage information.

Report to the IRB, the FDA and Manufacturer:
If the Emergency Exemption is exercised, the IRB must be notified via the Emergency Use pathway in eIRB (check "Emergency Use of Investigational Agent" in section 1.01). There is an option to notify the IRB prior to the use. Regardless of whether an initial notification is file the investigator must complete a 5-day Report so that the IRB can ascertain that the use was appropriate. The investigator must report the use, including adverse events to the FDA.

Emergency Use of Investigational Devices

The FDA has not objected if a physician chooses to use an unapproved device in an emergency, provided that the physician later justifies that an emergency actually existed. Each of the following conditions must exist to justify emergency use of an investigational device:

1. the patient is in a life-threatening condition that needs immediate treatment;
2. no generally acceptable alternative for treating the patient is available; and
3. because of the immediate need to use the device, there is no time to use existing procedures to get FDA approval for the use.

• Before Emergency Use
• After Emergency Use of an Unapproved Device

FDA's Expectations for Investigator-Sponsors Holding a Single Subject IND or IDE

When an investigator holds the IND or IDE for a single subject, they are none-the-less the study sponsor. The FDA's enumerates the responsibilities of sponsors at 21 CFR 312.50 - 70 (Subpart D) Responsibilities of Sponsors and Investigators. An example of the type of letter that the FDA will send confirming that they have granted the single-subject IND are included below.

Exception From Informed Consent Requirement

Even for an emergency use, the investigator is required to obtain informed consent of the subject or the subject's legally authorized representative unless both the investigator and a physician who is not otherwise participating in the clinical investigation certify in writing all of the following 21 CFR 50.23 Exceptions from the general requirements:

1. The subject is confronted by a life-threatening situation necessitating the use of the test article.
2. Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject.
3. Time is not sufficient to obtain consent from the subject's legal representative.
4. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject's life.

If, in the investigator's opinion, immediate use of the test article is required to preserve the subject's life, and if time is not sufficient to obtain an independent physician's determination that the four conditions above apply, the clinical investigator should make the determination and, within 5 working days after the use of the article, have the determination reviewed and evaluated in writing by a physician who is not participating in the clinical investigation. The investigator must notify the IRB within 5 working days after the use of the test article (21 CFR 50.23(c)).