FDA Expanded Access Program: A Comprehensive Guide

Sushmitha Das

We are witnessing innovation across the healthcare industry, whether it’s medicines and drug discovery, biotechnology, or digital health, to provide new treatments and diagnoses of diseases.

Yet, there are people facing serious and life-threatening illnesses with no available medication or appropriate treatment options. For these patient populations, the FDA has introduced Expanded Access, or “compassionate use” as a potential pathway to access medical products under development. The investigational medical products comprise drugs, biologics, or medical devices that have not yet been approved or cleared by FDA, and their safety and effectiveness for specific use are not determined.

To gain access to investigational medical products, patients must meet the below criteria:

  • The patient has a serious condition or whose life is immediately threatened
  • No satisfactory alternative therapy is available
  • Enrolling in a clinical trial is not possible (Examples include patient ineligibility, lack of required clinical trials, and lack of feasibility) 
  • The potential benefit patient can achieve justifies the possible risks involved in the treatment
  • Patient taking the IMP will not in any way affect the investigational trials

Familiarize yourself with some terms and definitions used in the context of the FDA Expanded Access Program to understand better.

1. Immediately life-threatening diseases:

This means a stage of a disease in which there is a reasonable likelihood of death occurring in a few months or in which premature death is likely without early treatment.

2. Serious condition:

A disease with morbidity that can have an impact on day-to-day functioning and if left untreated will progress to a serious condition.

3. Investigational medical product:

This includes investigational new drugs, biologics, and investigational devices. An investigational new drug means a drug used in a clinical investigation. This also includes a biological product used in vitro for diagnostic purposes.

4. Investigational device exemption (IDE):

This allows the use of investigational medical devices in a clinical study.

5. Investigator:

A licensed physician under whom an investigational drug or biologic is administered for expanded access use.

6. Sponsor:

A person who initiates a clinical investigation and takes responsibility for the process. The sponsor can be an individual, pharma company, governmental agency, academic institution, private and other organizations.

7. Sponsor-Investigator:

A person who initiates and conducts (alone or with others) a clinical investigation. The term includes only an individual and not a corporation or agency.

Different roles in FDA Expanded Access Program

Before we dive into the benefits and requirements of the Expanded Access Program in detail, it’s important to understand the responsibilities of stakeholders involved in the ecosystem apart from the patients. 

Physician

A licensed physician is responsible for overseeing the patient’s treatment and works with other stakeholders, including industry (explained later), and filing requests to FDA and IRB. A physician is also in charge of patient care and reporting.

Industry (Company)

The industry refers to the company which develops the investigational medical product but may not be the manufacturer of the product. The industry provides the investigational medical products and also sponsors the EA and on behalf of sponsor-investigator allows the FDA to cross-reference to their industry IND or IDE. The company also provides required product information to the sponsor-investigator for supporting an EA request. 

Institutional Review Board (IRB)

IRB is a board or committee designated to review, approve, and conduct periodic reviews of biomedical research including human subjects. For EAP, IRB reviews the protocol submitted and consent, ensuring the patient is informed about the treatment and its nature.

FDA

FDA reviews the EA request and determines whether the treatment can proceed or not.

What are the different types of FDA Expanded Access?

Under the FDA regulations, there are three categories of expanded access, based on the size of the treatment population. Each of these categories has two regulatory submissions: a new investigational new drug application (IND) and a protocol (treatment plan) submitted as a protocol amendment to an existing IND. 

Here are the three categories of the FDA Expanded Access Program.

1. Individual Patient Access

Single Patient IND or Individual Patient Expanded Access IND:

In this category, investigational medical products can be used by a single patient submitted as a protocol under a new IND. There is a 30-day waiting period for treatment unless the FDA notifies the sponsor.

Single Patient Protocol or Individual Patient Expanded Access Protocol:

Individual patient expanded access protocol is submitted by a single user as a new protocol to an existing IND by the sponsor of the IND. It is to be noted that several patients may follow the same protocol. While there is no waiting period before treatment begins, the protocol must be received by FDA and approval from IRB should be obtained before the treatment may begin.

1a. Individual Patient Access in an Emergency

For emergency situations that require a patient to be treated before submission, the FDA provisions an emergency expanded access use or emergency access. to help individual patients to access investigational drugs and biologics. 

When there is not sufficient time to secure IRB review before treatment, the emergency use of the investigational drug must be reported to the IRB within the 5 working days. The written submission (individual patient expanded access IND and protocol) should be submitted within 15 business days of the authorization.

Emergency INDs and protocols are subcategories of Individual Patient Access.

Emergency IND: 

This category is for access to an investigational drug for single patient use in an emergency submitted as a protocol under a new IND. Physicians can request treatment and authorization by rapid means of electronic communication such as telephone. Once FDA authorizes access, treatment can be started immediately. 

Emergency protocol:

Access requests can be submitted as a new protocol to an existing IND by the sponsor of the IND. Similar to emergency IND, treatment requests and authorization can be done via telephone or any other communication means.

2. Intermediate-sizepatient population access

This type of expanded access defines access to investigational drugs (and biologics) for use by intermediate-sized patients (more than a single patient but less than those treated under a typical treatment IND or protocol). 

Intermediate-size patient population expanded access IND: 

This category provides Intermediate-size patients with access to investigational drugs and biologics which is submitted as a protocol under a new IND. There is a 30-day waiting period before treatment begins and the investigational product can be under development for marketing. 

Intermediate-size patient population expanded access protocol: 

Access to investigational drugs including biologics for use by more than one patient submitted as a protocol to an existing IND by the sponsor of the existing IND. The protocol must be received by FDA and approved by IRB before treatment starts, but there is no 30-day waiting period. 

3. Expanded Access for widespread use

Treatment IND:

This access type provides access to an investigational drug for use by a large population submitted as a protocol under a new IND. The investigational product should be under active development for marketing.

Treatment Protocol: 

Request access to an investigational drug for use by a widespread population as a protocol to an existing IND. This type of access protocol is unlike others due to the fact that there is a 30-day waiting period before the treatment begins. If the FDA approves, the treatment can begin earlier.

Expanded Access for medical devices

EAP for medical devices has similar types and few distinctions. For devices, single or small treatment group access is called Compassionate Use, whereas the process for a large treatment group is referred to as a Treatment IDE (Investigational Device Exemption). To know more about EAP for investigational devices, visit here.

What are the benefits of FDA Expanded Access? 

Patients

The Expanded Access Program is primarily focused on patients, providing them an opportunity to receive potentially beneficial treatments in the investigation stage with limited access. It plays a critical role in offering care for patients with rare diseases who can’t find appropriate drugs or have exhausted available treatments. 

In addition, EAP can also bridge the gap between the drug development phase and the final approval of a drug. 

At FDA’s The Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research combined, FDA receives over 1000 requests for various types of Expanded Access every year. 

According to CDER’s expanded access submission receipt reports for INDs and Protocols from 2015-2019, the EAP beneficiaries are increasing each year. 

Here’s the graph depicting IND submissions and patients allowed to proceed.

Sponsors

The data from EAP is advantageous for drug manufacturers in many ways. The treatment benefit in patients demonstrated by the data may lead to increased expanded use of the drug. The manufacturer can obtain efficacy and safety data from patients treated under EAPs which can accelerate the final approval of the drug. Similar is the case for medical devices.

Physicians

Through EAPs, physicians can provide additional treatment options to patients and offer better care.

How to submit EAP requests?

Generally, a licensed physician is responsible for requesting expanded access to investigational drugs (including biologics) for their patients (Below given is a table showing who all may request expanded access to investigational drugs). It is to be noted that the physician must obtain permission from the drug manufacturer first for expanded access to investigational products.

A critical component of the expanded access application is a letter of authorization (LOA) received from the commercial developer of the drug. This grants the FDA to reference the application for information related to the drug, including chemistry, manufacturing details, pharmacology and toxicology information. 

FDA-Expanded-Access-Program-img

Here’s a checklist for physicians while requesting FDA Expanded Access to investigational drugs: 

  1. Determine if the patient is eligible for a clinical trial or not. Physicians can check ongoing clinical trials on ClinicalTrials.gov. If the patient(s) is eligible for participation, they can enroll in the trial and go ahead with it. 
  1. Determine the patient population size for treatment and evaluate the status of the drug using the FDA’s criteria. 
  1. Determine if the expanded access requires a new IND or can be amended to the existing IND. A licensed physician can apply to the FDA for a new IND or function under an existing IND held by a drug manufacturer or another physician. 
  1. Ensure appropriate monitoring of patient safety by maintaining reports and records of the program.

Step-by-step guide for FDA Expanded Access request submission (non-emergency individual patient and intermediate-size population IND)

1. Request LOA: 

A licensed physician has to first request an LOA from the medical product developer. This will be obtained typically from the regulatory affairs official of the company. If an LOA is not available, physicians can submit sufficient information with the forms for expanded access.

2. Submit Form 3926/ Forms FDA 1571 and 1572: 

For individual patient IND, physicians should submit Form 3926 along with the LOA to FDA. In the case of intermediate-size population IND, Forms 1571 and 1572 should be submitted. These forms can also be used for single patient expanded access submissions, however, Form 3926 is developed specifically for these requests.

3. IRB approval

Obtain IRB approval as per 21 CFR Part 56. A physician using Form FDA 1571 may also include a separate waiver request with the application. Here’s an official database for registered IRB’s.

4. Informed Consent

Physicians should collect Informed Consent from the patient or their legal representative using a consent form approved by the IRB.

5. Begin treatment

For both individual patients and intermediate-size population INDs, the treatment can begin 30 days after the application is received by FDA. It may also proceed earlier if notified by the FDA.

6. Follow up

Follow-up reports, including safety reports, amendments, summaries, and annual reports, are submitted using the same form as the original expanded access request, either Form 3926 or Form 1571.

In the case of emergency use of an investigational drug or biologic, the physician has to request FDA emergency use authorization by telephone or any other rapid means of communication. If authorized by the FDA, treatment can be initiated. It is also mandatory to notify IRB within 5 business days after the beginning of treatment. Form FDA 3926 can be submitted within 15 business days of FDA emergency use authorization.

Expanded access requests for medical devices do not require the use of an official FDA form. To learn more, visit here.

How BTC digitized and created the FDA Expanded Access eRequest

Until recently the entire EAP request process was done offline, using paper-based methods. To expedite the process and increase efficiency, the FDA partnered with the Reagan-Udall Foundation (RUF) to shift to digital workflows and electronic submissions and provide resources to physicians virtually. 

BTC has developed the first-of-its-kind web application ‘Expanded Access eRequest’ to digitize the end-to-end non-emergency individual use of an expanded access program application. Through the app, physicians can submit the initial expanded access IND applications known as Form FDA 3926 to the FDA. It also enables them to review and track the applications. 

The software application that we built eliminates manual touchpoints and paper-based operations while ensuring scalability, efficiency, and extensibility. Our platform is also designed to safeguard undue exposure of sensitive information and adhere to healthcare  industry regulations such as 21 CFR Part II, FISMA, and HIPAA-grade security controls.

The web app is compatible across browsers and devices allowing physicians and federal officials to access the app on any device. Using API Integration, the app connects with ClinicalTrials.gov and RUF Company Navigator, thereby streamlining the process of compiling relevant documents and information for the IND application. Users can check information on active clinical trials, investigational product company’s contact information, and instructions for requesting permission to use the investigational therapy and obtaining informed patient consent.

The digital future ahead

FDA expanded access brings hope for patients with no available treatment options. With efficient digital workflows and improved clarity in the regulatory processes, the FDA expanded access program will continue to create new pathways to life. 

At BTC, we are committed to helping stakeholders in the healthcare industry to provide the highest quality of care for patients. We have demonstrable experience working with govt, private and other healthcare organizations, enabling them to embrace digital transformation. We specialize in building and maintaining robust, user-friendly web & mobile applications, enterprise-grade software applications, and digital platforms. Our solutions are compliant with HIPAA, SOC2, FISMA, HL7 standards, and other regulatory compliance and guidelines. To know more, visit.

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