Emergency Use, Compassionate Use &Expanded Access Programs

An Investigational New Drug (IND) is a substance that has been tested in the laboratory and has been approved by the U.S. Food and Drug Administration (FDA) for testing in people.

An IND application is a request for authorization from the Food and Drug Administration (FDA) to administer an investigational drug or biological product to humans. Authorization must be secured prior to interstate shipment and administration of any new drug or biological product that is not the subject of an approved New Drug Application or Biologics/Product License Application.

There are three IND types:- Investigator IND- Emergency Use IND- Treatment IND (Compassionate use/Expanded Access)

Investigational New Drug

An approved investigational device exemption (IDE) 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.

There are 2 IDE types:- Traditional IDE Study- Expanded Access

Investigational Device Exemption

Emergency UseEmergency Use: The use of a test article on a human patient in a life-threatening or severely debilitating circumstance where no standard medically acceptable treatment is available and there is not sufficient time to obtain full IRB approval for use of the test article to treat the patient [21 CFR 56.102(d)].

- Life-threatening: Diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted.

- Severely debilitating: Diseases or conditions that would likely cause major irreversible morbidity (e.g. loss of a limb, paralysis or stroke).

- Note: A life-threatening and/or severely debilitating condition does not necessarily mean that the condition is immediately life-threatening or may imminently result in death or irreversible morbidity. Rather, the patient must be in a situation requiring prompt administration of the test article before review at a convened meeting of the IRB is feasible and any treatment delay will have a significant deleterious effect on the patient. Consequently, premature death and/or persistent morbidity are likely.

• A patient with pan-resistant Mycobacterium abscessus chronic mastoiditis. Patient currently on two intermediate active agents, cefoxitin and linezolid

• Mycobacterial infectious disease experts recommended the use of Clofazimine (expected to be the only active agent against her infection)

• Research pharmacist at CHMC spoke with FDA regarding next steps. Was put into contact with Novartis (supplier of Clofazimine) to initiate next steps for Emergency Use.

• Contacted IRB about an emergency use study and what was required from the IRB (provided with the Emergency Use of a Test Article Report and Emergency Use Consent Template - these are not found on RSS)

• Novartis had a specific Single Patient IND (SPIND) request form which was used to assess patient’s eligibility for SPIND for Clofazimine.

• Completed SPIND, FDA Form 3926 OR FDA Forms 1571 and 1572, physician’s CV, and a pre-paid UPS or FedEx shipping label. Documentation of IRB’s approval of emergency use of drug.

• Once treatment started, inform IRB of this - there is a timeline for reporting to the IRB. (refer to policy)

Emergency Use Example

Please refer to UNMC IRB Policy #6.4 - Emergency Use of a Test Article

1. Contact the sponsor of the investigational drug or device to determine ability to use for patient. Find out from the sponsor who will be submitting the IND application OR Investigational Device Exemption

Steps to Prepare an Emergency Use Submission

2. If Investigator will submit IND: Go to www.fda.gov and type in “Emergency Use IND” in the Search box. This will bring up guidance on submission of an Investigational New Drug application and the contact information for the individuals at the FDA who need to be contacted by the investigator to request approval.

Steps to Prepare an Emergency Use Submission

3. Contact the Institutional Review Board as described in Section 7.0 of Policy #6.4.

4. Request from IRB the emergency use consent template. To be emailed from IRB administrator.

Steps to Prepare an Emergency Use Submission

5. Collect the following documents to be submitted to the Pediatric Research Office:a. Email approval from IRB for emergency useb. Letter to IRB chair. Template letter: Download the IRB letter

template (Complete all sections highlighted in red. After complete, sign and submit with other requested documents.)

c. Signed and dated curriculum vitae within the last 2 years

Steps to Prepare an Emergency Use Submission

Steps to Prepare an Emergency Use Submission

6. If investigator to submit IND, collect the following documents from sponsor to be submitted to Pediatric Research Office:

a. Contact information for representative at pharmaceutical companyb. Letter of authorizationc. Sponsor agreement/contractd. Investigational brochure and/or pharmacy manuale. Sponsor’s consent templatef. Any other documents that sponsor is requiring to be completed

Pediatric Research Office can assist with revisions to sponsor’s consent template. PRO can also assist with submission of regulatory documents to IRB, Sponsor, and FDA.

Steps to Prepare an Emergency Use Submission

7. Investigator to contact pharmacy regarding plan for treatment:

UNMC investigational pharmacy number – Daytime #: 402-559-5255, After hours #: 402-888-3418

CHMC investigational pharmacy number – 402-955-5470 (ask for pharmacy manager on call)

Steps to Prepare an Emergency Use Submission

8. Per Policy 6.4, Section 7.6: If a test article is an investigational drug or biologic, and there is sufficient time, the treating physician must:

a. Contact the Chair of the P&T Committee/designee and obtain a P&T emergency use approval –

- UNMC: Jon Beck (JBeck@nebraskamed.com) will initiate the P&T review at the time of contact about the emergency use request,

- CHMC: Investigational pharmacist (402-955-5470 - ask for pharmacy manager on call) will discuss with treating physician the processes for P&T review.

a. Notify the Executive Director of the Pharmacy or Investigational Drug Pharmacist of the emergency use, and provide information concerning financial responsibility for the pharmacy costs of the test article.

Steps to Prepare an Emergency Use Submission

Upon completion of all tasks, please contact Ashley Servais, PRO

manager, at ashley.servais@unmc.edu

or 402-559-2511.

Steps to Prepare an Emergency Use Submission

* If request is after hours you may not get a response until next business day. *

Compassionate Use & Expanded Access Programs

Compassionate Use & Expanded Access Programs: FDA regulations at 21 CFR 312.300 (subpart I) allow certain individuals not enrolled in clinical trials to obtain expanded access to investigational drugs through various expanded access programs (EAPs). All expanded access programs must meet the basic criteria in 21 CFR 312.305(a). Specifically the FDA must determine:

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.

Please refer to IRB Policy #6.1 – Research Involving Investigational and Marketed DrugsExpanded Access Program - Section 7.0

1. Contact the sponsor of the investigational drug/device to determine ability to use for patient. Find out from the sponsor who will be submitting the Investigational New Drug/Device (IND) application.

Steps to Prepare a Compassionate Use or Expanded Access Submission

2. If Investigator will submit IND: Go to www.fda.gov and type in “Compassionate Use IND” or “Expanded Access” in the Search box. This will bring up guidance on submission of an Investigational New Drug application.

Steps to Prepare a Compassionate Use or Expanded Access Submission

3. Collect the following documents to be submitted to the Pediatric Research Office: Email approval from IRB for compassionate use Letter to FDA. Template letter: Download the FDA

letter template. (Complete all sections highlighted in red. After complete, sign and submit with other requested documents.) Signed and dated curriculum vitae

Steps to Prepare a Compassionate Use or Expanded Access Submission

Steps to Prepare a Compassionate Use or Expanded Access Submission

4. If investigator to submit IND, collect the following documents from sponsor to be submitted to Pediatric Research Office:

a. Contact name for representative at pharmaceutical companyb. Letter of authorizationc. Sponsor agreement/contractd. Investigational brochure and/or pharmacy manuale. Sponsor’s consent templatef. Any other documents that sponsor is requiring to be completed

Pediatric Research Office can assist with revisions to sponsor’s consent template. PRO can also assist with submission of regulatory documents to IRB, Sponsor, and FDA.

Steps to Prepare a Compassionate Use or Expanded Access Submission

Upon completion of all tasks, please contact Ashley Servais, PRO

manager, at ashley.servais@unmc.edu

or 402-559-2511.

Steps to Prepare a Compassionate Use or Expanded Access Submission

* If request is after hours you may not get a response until next business day. *

• Make sure the study medication coverage is known and documented in the IRB application/consent. This includes any financial risk the patient may incur.

• Even if sponsor says no contract/agreement is needed you need to at least have legal review and sign off.

• Make sure to evaluate emergency use request as the IRB may consider it as a non-emergency. If this is the case it would go through as a compassionate use/EAP application. The board can be called to have an emergency meeting to get this approved faster.

Special Considerations

Contact Us

https://www.unmc.edu/chri/pro/investigator-resources/index.html

https://www.childrensomaha.org/research/child-health-research-institute-childrens-unmc/

Email: PedsResearch@unmc.edu

Questions?