Abstract
The Oncology Center of Excellence at the U.S. Food and Drug Administration launched Project Facilitate on May 31, 2019, to assist oncology health care providers with Expanded Access requests for investigational drugs. Expanded Access, sometimes called “compassionate use,” is a regulatory pathway for physicians caring for patients who have a life‐threatening condition or a serious disease to gain access to an investigational drug for treatment when no comparable or satisfactory alternative treatment options are available. Herein we describe the Project Facilitate program and the process for requesting Expanded Access to an investigational drug.
Keywords: Expanded Access, Food and Drug Administration, Project Facilitate, Oncology
Short abstract
Expanded Access, sometimes called “compassionate use,” is a regulatory pathway for physicians caring for patients who have a life‐threatening condition or a serious disease to gain access to an investigational drug for treatment when no comparable or satisfactory alternative treatment options are available. This article describes the Project Facilitate program and the process for requesting Expanded Access to an investigational drug.
Introduction
The U.S. Food and Drug Administration's (FDA) Expanded Access program allows physicians to request access to investigational drugs for the treatment of patients who have serious or life‐threatening diseases when no satisfactory therapies are available and the patient is not eligible to enroll in a clinical trial [1]. Investigational drugs have not yet been approved by the FDA, and the FDA has not determined these products to be safe and effective for their intended use. The investigational drug may, or may not, be effective in the treatment of the condition, and the safety of the drug has not been fully characterized. To reduce and remove barriers to Expanded Access, the Oncology Center of Excellence (OCE) launched Project Facilitate. Project Facilitate staff are available by telephone and e‐mail to provide step‐by‐step support to oncology health care providers seeking Expanded Access to investigational drugs for their patients.
FDA Efforts to Reduce Barriers to Expanded Access
Prior to starting Project Facilitate, the OCE held a public workshop in collaboration with the Reagan‐Udall Foundation to identify perceived barriers to Expanded Access [2]. The barriers identified were as follows: lack of awareness of the Expanded Access process (e.g., how and where to submit a request), the perception that Expanded Access request procedures are burdensome, the perception that requests are frequently denied, the perception that Institutional Review Board (IRB) requirements are onerous, and that some hospitals lack administrative support to submit Expanded Access requests.
FDA reduced barriers to Expanded Access by developing a streamlined Expanded Access form, FDA 3926, which by checking box 10b offers the option to request IRB concurrence of the Expanded Access protocol by an IRB designee, as opposed to requiring review by the whole IRB committee [3]. Panel 1 provides details of Form FDA 3926. To further reduce barriers, FDA's OCE created Project Facilitate, a call center staffed with oncology professionals to assist providers with Expanded Access requests by telephone and e‐mail [4]. Project Facilitate staff perform expedited reviews of Expanded Access requests for drugs regulated by the Office of Oncologic Diseases. Lastly, the Reagan‐Udall Foundation launched a streamlined electronic request form (eRequest) that providers can use to file new requests for non‐emergency Expanded Access to investigational drugs [5].
Panel 1: Form FDA 3926.
Available at https://www.fda.gov/media/98616/download
Initial Expanded Access Request
Reporting Requirements for Expanded Access (Box 9)
(Check the box that corresponds to your submission):
Initial Safety Report
Follow‐up Safety Report
Annual Report
End‐of‐Treatment Summary
Change in Treatment Plan
General Correspondence
Response to FDA Request for Information
Response to Clinical Hold
Expanded Access
Research and development within oncology provides new investigational drugs faster than ever before, but there is a lag time from proof of concept and clinical trials to FDA approval. Expanded Access of investigational drugs can be used for patients with serious conditions who lack therapeutic alternatives. Providers caring for patients who meet the criteria for Expanded Access can determine if there are investigational drugs with the potential to provide clinical benefit for their patient. An example within oncology of how Expanded Access can be used is for a patient with heavily treated cancer with a mutation that is targetable by an investigational drug. The determination of potential benefit can be based upon mechanism of action and nonclinical and clinical studies.
Project Facilitate was designed to provide oncology health care providers quick and easy access to regulatory professionals who can assist them with the submission of Expanded Access requests. Requests for Expanded Access outside of oncology will in most cases be reviewed by an FDA Division outside of an oncology review division.
How to Request Expanded Access for Your Patient
Once an investigational product is identified that provides a reasonable expectation of clinical benefit for the patient, the oncologist should contact the drug company to request access to the investigational drug and a letter of authorization (LOA). The LOA allows FDA to reference the drug company's Investigational New Drug application (IND) for product chemistry, manufacturing and controls process, nonclinical data, and clinical data so that the health care provider does not need to submit these data. Contact information for drug companies can be found on their respective Web sites or on the Reagan‐Udall Expanded Access (EA) Navigator Web site under the “Company Directory” tab [5]. Next, the oncologist should submit Form FDA 3926 and the LOA to FDA for review either by e‐mail to ONCProjectFacilitate@FDA.hhs.gov or by the Reagan‐Udall eRequest (https://erequest.navigator.reaganudall.org/#/home/landing) [5]. Then, the oncology health care provider should submit the treatment plan to an IRB for approval. If a provider does not have access to an IRB, they can consult the Reagan‐Udall Foundation EA Navigator Web site for a list of independent IRBs (free or for fee) that offer review services for Expanded Access requests.
Prior to administration of the drug, the health care provider needs to obtain FDA approval of the Expanded Access request, the patient's written informed consent, and IRB approval [6, 7]. (Regarding informed consent, 21 CFR §50.27 states that “… informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject's legally authorized representative at the time of consent. A copy shall be given to the person signing the form.”)
What Happens When the Expanded Access Request Is Submitted to FDA?
In general, FDA reviews the cross‐referenced IND provided in the company's LOA to ensure that the investigational product meets safe manufacturing and control standards and available nonclinical and clinical information support the treatment use. FDA reviews the Form FDA 3926 to ensure that the physician is licensed and qualified to treat the patient, the proposed dose and schedule of the investigational product are reasonable, and the plans for patient monitoring and toxicity management are adequate. When the review of the Expanded Access request is complete, FDA issues a letter to the treating oncologist stating that the planned treatment is safe to proceed and that the Expanded Access IND has been approved.
In emergency situations, FDA can grant an emergency Expanded Access request without a complete paperwork submission. After FDA grants the request, treatment can begin after informed consent is obtained from the patient. Health care providers are allowed 5 working days from the date of emergency treatment to notify the IRB of investigational drug use [6]. Providers have 15 working days from the date of FDA authorization to submit the completed paperwork for the Expanded Access submission.
Required Reporting for Expanded Access
Once an Expanded Access IND is granted, FDA requires submission of safety reports, annual reports, and an “end‐of‐treatment” summary [8]. Safety reports for Expanded Access are required only for serious and unexpected adverse reactions when there is a suspected causal relationship to the investigational drug [6]. Serious adverse reactions involve a death, are life‐threatening, require hospitalization, cause disability or permanent damage, or cause a birth defect [9]. Annual reports should be brief and include treatment dates, tolerability, and patient response. Similarly, end‐of‐treatment summaries should include treatment dates and tolerability, including any adverse events and patient response. When treatment concludes, the oncologist should withdraw the Expanded Access IND.
Summary: FDA Oncology Expanded Access Requests
FDA's Project Facilitate helps oncology health care providers by assisting them in navigating the Expanded Access process, making Expanded Access requests easier to submit, and by providing expedited review of Expanded Access requests for oncology drugs. Prior to Project Facilitate, Expanded Access requests for oncology products were received by various review divisions within FDA, and although the Expanded Access requests were reviewed in a timely manner, submission and review of requests was not centralized, sometimes causing delays. Project Facilitate makes the Expanded Access process for oncology drugs more efficient as a single point of contact for receipt, review, and processing of the majority of oncology Expanded Access requests. Within the first year (May 31, 2019, to May 31, 2020), Project Facilitate received 710 telephone calls, 5,836 e‐mails, and almost 800 oncology Expanded Access requests, 100 of which were for pediatric patients. The majority of complete submissions were reviewed and allowed to proceed in less than 1 business day.
Conclusion and Contact Information
As part of its mission to expedite the development and clinical review of oncology products, the FDA Oncology Center of Excellence established Project Facilitate, a program to assist oncology health care providers in requesting access to investigational therapies for patients with cancer. Panel 2 provides contact information for health care providers and their teams to submit Expanded Access requests for oncology products.
Panel 2: Expanded Access Information.
| Oncology Expanded Access Information for health care providers or regulatory professionals |
Project Facilitate 240‐402‐0004 8:00 a.m. to 4:30 p.m. EST Monday through Friday |
| E‐mail Oncology Expanded Access Requests |
E‐mail: OncProjectFacilitate@fda.hhs.gov Attach request documents to the message |
| After Hours Expanded Access Requests |
FDA's Emergency Call Center 866‐300‐4374 |
| Information for patients and families |
FDA's Division of Drug Information 301‐796‐3400 or 855‐543‐3784 E‐mail questions to druginfo@fda.hhs.gov |
Author Contributions
Conception/design: Barbara Scepura, Mitchell Chan, Tamy Kim, Jessica Boehmer, Kirsten B. Goldberg, Richard Pazdur
Manuscript writing: Barbara Scepura, Mitchell Chan, Tamy Kim, Jessica Boehmer, Kirsten B. Goldberg, Richard Pazdur
Final approval of manuscript: Barbara Scepura, Mitchell Chan, Tamy Kim, Jessica Boehmer, Kirsten B. Goldberg, Richard Pazdur
Disclosures
The authors indicated no financial relationships.
Acknowledgments
The authors would like to thank Timothy Kim, of FDA's Center for Drug Evaluation and Research Data Analytics, for assistance with the data on oncology Expanded Access requests.
Disclosures of potential conflicts of interest may be found at the end of this article.
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References
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