When standard treatments have been exhausted and clinical trials aren’t an option, patients with serious conditions may still have a potential pathway forward. Compassionate use and expanded access offer a regulated route to gain access to investigational drugs, biologics, or medical devices that haven’t yet received marketing approval. These investigational medical products are considered unapproved drugs and may cause unexpected serious side effects.
These pathways exist for patients facing a serious or immediately life threatening disease who lack comparable or satisfactory alternative therapy options. In the United States, the FDA’s Expanded Access Program oversees this process, first formalized in regulations in 1987 and substantially updated in 2009. A formal compassionate use program was established in the US in 1987 in response to requests from HIV/AIDS patients. The FDA plays a central role in reviewing requests, providing guidance, ensuring patient safety, and facilitating access to unapproved drugs while maintaining regulatory oversight. However, access to investigational treatments requires not only FDA review and authorization but also the active involvement and cooperation of drug companies and health care providers. The numbers are reassuring: FDA authorizes approximately 99% of expanded access submissions and typically reviews non-emergency requests within days. Emergency requests often receive responses in less than 24 hours.
The FDA cannot require a manufacturer to provide its drug under expanded access, which raises ethical concerns about patient access to investigational treatments.
Key points to understand:
- Expanded access provides access to investigational products outside of available clinical trials
- The pathway serves patients with serious disease or immediately life threatening conditions
- FDA oversight helps balance potential patient benefit against potential risks
- Both drugs and medical device expanded access pathways exist
What Is Compassionate Use (Expanded Access)?
The terms “compassionate use” and “expanded access” are often used interchangeably. However, expanded access is the formal regulatory term the FDA uses in its guidance and regulations.
- Expanded access allows access to an investigational medical product still under clinical development, such as a drug, biologic, or medical device under an Investigational New Drug (IND) application or Investigational Device Exemption (IDE)
- Unlike clinical trials, the primary goal of expanded access is treatment for the patient—not data collection to support marketing approval
- Investigational therapies accessed this way may include drugs, biologics (such as gene therapies, monoclonal antibodies, or cellular therapies), and medical devices
- These pathways typically address serious conditions like advanced cancers, progressive neurologic disorders, or rare diseases
- Expanded access is distinct from enrollment in clinical investigations designed to generate approval data
- Expanded access is often used for individual patients who cannot participate in clinical trials, especially in urgent or emergency situations
Accurate and comprehensive drug information is essential for physicians and patients when considering or requesting investigational drugs under expanded access, ensuring informed decisions and compliance with FDA guidance.
Regulatory Background and FDA Oversight
FDA’s expanded access regulations have evolved significantly over the past few decades. The agency first issued formal rules in 1987, then substantially revised them in August 2009 to clarify categories, criteria, and procedures under 21 CFR Part 312 Subpart I. These updates created the structured framework that exists today.
The 21st Century Cures Act of 2016 added transparency requirements. The law requires many drug and biologic manufacturers to publicly post expanded access policies, including how they evaluate requests and anticipated response timelines. This helps patients and physicians understand what to expect when seeking expanded access from specific companies.
FDA’s role centers on safety and oversight. The agency reviews each expanded access request to assess the risk-benefit balance, ensuring that providing early access will not compromise ongoing pivotal trials or product development. FDA receives roughly 1,000–1,500 expanded access submissions each year and allows nearly all to proceed—often after suggesting protocol adjustments or dosing modifications to enhance patient safety.
Regulatory framework summary:
- 21 CFR Part 312 Subpart I governs expanded access for drugs and biologics
- 21 CFR Part 812 covers medical device expanded access under IDE regulations
- The 21st Century Cures Act mandates public posting of manufacturer policies
- FDA guidance documents address charging, intermediate populations, and treatment use
Access to Investigational Drugs
For patients facing a serious or immediately life threatening disease, gaining access to investigational drugs can offer hope when all satisfactory alternative therapy options have been exhausted. The FDA’s expanded access program is specifically designed to provide a potential pathway for those who cannot participate in clinical trials and have no other comparable or satisfactory alternative therapies available.
Access to investigational drugs through expanded access is not automatic, but the process is structured to prioritize patient safety while offering a chance at potential benefit. A licensed physician plays a central role in requesting expanded access, evaluating whether the patient’s disease or condition meets the criteria, and determining if the potential patient benefit justifies the potential risks involved. The physician must also confirm that the patient is not eligible for ongoing clinical trials and that no satisfactory alternative therapy exists.
There are several ways patients may gain access to investigational drugs under the expanded access program. Individual patient expanded access is often used when a single patient urgently needs a therapy that is still under investigation, especially in emergency situations. For groups of patients with similar serious or immediately life threatening conditions, intermediate size patient groups may be eligible for access when clinical trials are not an option. In cases where a drug shows promise for widespread treatment use but is not yet approved, the expanded access process can allow broader patient populations to benefit while the drug continues through the regulatory pathway.
The expanded access process involves several important steps to ensure patient safety and regulatory compliance. The treating physician submits a detailed request to the FDA, outlining the patient’s medical history, the investigational product, and the rationale for its use. Institutional Review Board (IRB) approval is required to protect patient rights and welfare, and informed consent must be obtained to ensure the patient understands the investigational nature of the treatment, potential risks, and any available alternatives.
The FDA reviews each expanded access request carefully, weighing the potential benefits against the potential risks, and considering whether the request might impact ongoing clinical investigations. Thanks to streamlined procedures and clear guidance, the agency is able to authorize the vast majority of expanded access submissions—often within days for non-emergency cases, and within hours for emergency requests.
For patients and families seeking expanded access, it’s important to work closely with a knowledgeable physician who can navigate the process, provide detailed information in the submission, and coordinate with the manufacturer and IRB. Additional resources, including the FDA’s expanded access web pages and patient advocacy organizations, can offer support and guidance throughout the journey.
Ultimately, the expanded access program exists to provide a potential pathway for patients with serious or immediately life threatening diseases to access investigational drugs when no satisfactory alternative therapy options remain. By following the expanded access process, patients and their physicians can explore every available option for care, while ensuring that safety and ethical standards are upheld.
Types of Expanded Access Pathways
The FDA recognizes three main categories for drugs and biologics: individual patient expanded access (including emergency use), intermediate-size patient population access, and treatment INDs or treatment protocols for widespread treatment use.
The appropriate expanded access request type depends on several factors: the size of the patient population, the stage of product development, and the urgency of the clinical situation.
- Individual patient access serves single patients with urgent needs
- Intermediate-size protocols cover small groups with shared characteristics
- Treatment INDs enable widespread treatment when development is advanced
- Medical device pathways include emergency use and compassionate use under IDE regulations
- Each pathway has distinct requirements and submission procedures
Individual Patient Expanded Access (Including Emergency Use)
Individual patient expanded access serves a single named patient when no satisfactory alternative therapy exists and clinical trial participation isn’t feasible. This might occur due to geographic barriers, strict eligibility criteria that exclude the patient, or trial closure.
The process differs based on urgency. Non-emergency single-patient INDs are submitted in advance through standard channels. Emergency use applies when there’s an immediately life threatening situation that doesn’t permit waiting for standard review timelines.
For most individual patient drug or biologic cases, the treating physician submits Form FDA 3926, introduced in 2016 to streamline paperwork. FDA estimates this form takes approximately 45 minutes to complete—a significant reduction from previous documentation requirements.
For emergency requests, the patient's physician can contact FDA’s emergency operations center at 866-300-4374 after hours. In immediately life-threatening cases, the FDA may grant emergency authorization over the phone, but the physician must still obtain manufacturer consent. The patient's physician is responsible for contacting the drug company to secure agreement to provide the investigational product, obtaining IRB approval, applying to the FDA, and securing informed consent from the patient. Review staff work with the patient's physician to obtain rapid authorization by phone, followed by written documentation within 15 working days. After emergency use, a written request must be submitted to the FDA to formally seek authorization.
Practical example: Consider a patient with refractory lymphoma who has exhausted approved treatment options. Their licensed physician identifies an investigational product in phase II trials that might help. The patient doesn’t qualify for the ongoing trial due to prior treatments. The physician contacts the manufacturer, confirms willingness to provide the product, completes Form FDA 3926, and submits it to FDA. In non-emergency situations, FDA typically responds within a few days.
Intermediate-Size Patient Population Access
Intermediate-size INDs cover more than one patient but not a large population. This pathway often serves patients with rare diseases or when available data suggest benefit for a specific subset who cannot easily enroll in existing trials.
Typical scenarios include:
- A small group of patients sharing a specific genetic mutation
- Patients who meet clinical criteria but face logistical barriers to trial participation
- Groups with similar disease characteristics where individual requests would be duplicative
Requirements largely mirror individual patient access: the patient’s disease must be serious, no satisfactory alternative can exist, the risk-benefit balance must favor use, and access should not unduly interfere with ongoing clinical investigations. However, intermediate-size protocols require more formal documentation.
Elements typically defined in intermediate-size protocols:
- Specific eligibility criteria for included patients
- Dosing regimen and administration procedures
- Monitoring plan and safety assessments
- Adverse event reporting procedures
- Treatment duration and stopping rules
Sponsors—often the drug manufacturer or an academic investigator—usually submit these requests. The resulting safety data can inform ongoing drug evaluation and development decisions.
Treatment INDs and Widespread Treatment Use
Treatment INDs or treatment protocols provide broader access to an investigational product that has completed at least one controlled trial suggesting effectiveness and remains under active development for marketing approval.
Historical examples illustrate how widespread treatment use has functioned. During the HIV/AIDS crisis in the late 1980s and 1990s, treatment INDs provided antiretroviral therapies to thousands of patients while confirmatory trials continued. More recently, certain oncology drugs have followed similar pathways during the 2000s while registration trials gathered final data.
Treatment INDs often coexist with phase III or registration trials. This requires careful design to avoid undermining enrollment or compromising the interpretability of pivotal study data.
- Treatment INDs typically require evidence from at least one controlled trial
- The product must be under active development with reasonable progress toward marketing approval
- Detailed risk management and reporting obligations apply
- FDA may permit cost-recovery provisions under specific regulations
- The pathway helps treat patients while sponsors pursue regulatory science requirements
Eligibility Criteria and Core Requirements
Several fundamental criteria apply across all expanded access pathways. Understanding these requirements helps patients and physicians assess whether requesting expanded access makes sense for their situation.
Core FDA criteria:
- Serious or immediately life threatening disease or condition
- No comparable or satisfactory approved alternative therapy options
- Inability to join a suitable clinical trial
- Potential patient benefit justifies the potential risks
- Access will not cause unacceptable interference with clinical development
Informed consent remains essential. Patients must understand the investigational status of the therapy, potential risks, the limited knowledge base, and any alternative options that might exist. This consent process should be documented thoroughly.
Throughout treatment, appropriate monitoring, adverse event reporting, and compliance with applicable IND or IDE regulations are required. These safeguards help protect patients while generating safety data that may assist physicians and sponsors going forward.
Step-by-Step Process for Patients and Physicians
The expanded access process begins when a patient and their physician recognize that standard options have been exhausted and clinical trial enrollment isn’t feasible. Here’s how the pathway typically unfolds in practice.
First, the patient’s physician identifies a potential investigational product and contacts the manufacturer to ask whether they’re willing to provide access. This initial outreach is critical—even when FDA criteria are met, manufacturers must agree to supply the product. If the manufacturer agrees to provide access, they typically share relevant clinical information and treatment protocols.
Next, the physician prepares and submits FDA paperwork. For individual patient drug or biologic requests, this usually means completing Form FDA 3926. The form captures essential information: patient diagnosis, prior treatments, rationale for the specific investigational product, proposed treatment plan, and the physician’s qualifications.
Simultaneously or shortly after, the physician obtains IRB approval. In emergencies, treatment may begin before formal IRB review, but documentation must follow within five working days. The IRB ensures ethical standards are maintained and patient rights protected.
Before treatment begins, the physician documents informed consent with the patient, discussing what’s known and unknown about the investigational therapy. Once FDA determines the request meets criteria and allows it to proceed, treatment can begin.
Realistic timelines:
- Non-emergency FDA reviews: typically a few days
- Emergency authorizations: often within hours, including nights and weekends
- IRB review: varies by institution, but emergency provisions allow flexibility
- Manufacturer response: depends on company policy and product availability
FDA often consults directly with physicians by phone or email to refine dosing, monitoring, or eligibility considerations before authorizing use. This collaborative approach helps optimize patient safety while facilitating access.
Manufacturer Policies, Costs, and the 21st Century Cures Act
Even when a patient meets FDA’s criteria, the manufacturer must agree to supply the investigational product. Companies may decline expanded access requests for legitimate reasons: limited drug supply, safety concerns based on emerging data, or potential impact on enrollment in pivotal trials needed to support marketing approval.
The 21st Century Cures Act changed the transparency landscape. The law requires many drug and biologic sponsors to post publicly available expanded access policies. These policies typically include contact information for expanded access requests, general criteria the company uses for evaluation, and anticipated timelines for responding. This helps physicians know what to expect when reaching out.
Cost considerations add complexity. Companies may provide access to investigational drugs free of charge, or they may seek FDA permission to recover certain direct costs. However, manufacturers cannot profit from unapproved products through expanded access. The product itself may come at cost or free, but associated medical care—administration, monitoring, lab work—often involves separate billing.
Policy and cost factors:
- Manufacturers are not obligated to provide access to investigational products
- Public policies help set expectations for patients and physicians
- Cost recovery is limited to direct costs when FDA permits
- Insurance may or may not cover associated medical services
- Logistics including shipping, storage, and administration require coordination
- Institutions handle billing for services while products may be provided separately
The ethical complexity deserves acknowledgment. Manufacturers balance the desire to assist physicians and treat patients against practical constraints and the imperative to complete trials that will enable broader access through approval.
Expanded Access vs. Clinical Trials vs. Right-to-Try Laws
Expanded access and clinical trials serve different purposes. Trials generate robust data through randomization and controls, contributing systematic evidence to regulatory science and drug application processes. Expanded access prioritizes individualized treatment with more limited data collection.
FDA generally encourages clinical trial enrollment as the preferred route whenever feasible. Trials offer systematic safety monitoring, contribute to medical knowledge, and provide potential benefit to participants. Expanded access use serves those who cannot participate in trials but still need access to investigational therapies.
Right-to-try laws represent another pathway. The federal Right to Try Act of 2018, along with various state laws, creates an alternative route outside FDA’s traditional expanded access oversight. Key features include completion of phase I trials, ongoing development, and diagnosis of an immediately life threatening disease.
High-level comparison:
- Expanded access: Involves FDA review, requires manufacturer agreement, includes IRB oversight, mandates adverse event reporting
- Clinical trials: Designed to diagnose monitor or treat while generating approval data, systematic protocols, randomization when appropriate
- Right-to-try: Limited FDA involvement, fewer procedural requirements, less established reporting infrastructure
Many manufacturers still prefer the FDA-supervised expanded access route even when right-to-try might apply. The expanded access framework provides clearer liability protections and established safety monitoring—factors that matter for both companies and patients.
Recent Developments, Guidance, and FDA Support Resources
FDA has taken steps to streamline expanded access and reduce barriers for treating physicians. Form FDA 3926, introduced in 2016, significantly reduced paperwork for single-patient INDs. The simplified form replaced a more burdensome documentation process that previously discouraged some physicians from pursuing access.
Multiple FDA guidance documents clarify expectations for different scenarios. These cover topics including expanded access to investigational drugs for treatment use, charging for investigational drugs under an IND, and considerations for intermediate-size patient populations. Guidance documents provide detailed information without the binding force of regulations. When considering compassionate use expanded access, it is important to evaluate the possible benefits and risks of investigational drugs or devices. Additionally, adverse events occurring during expanded access can lead to clinical holds, which may impact the overall drug development program.
Available resources:
- FDA Patient Affairs staff can assist physicians and patients with questions
- Division project managers help navigate specific therapeutic areas
- Dedicated FDA web pages provide instructions on “Expanded Access: How to Submit a Request”
- Contact FDA’s Emergency operations for urgent after-hours situations at 866-300-4374
- Manufacturer websites often list expanded access contact points per Cures Act requirements
FDA’s commitment to provide access extends to operational support. After-hours availability through the emergency call system ensures that patients with immediately life threatening conditions can receive timely responses regardless of when the need arises.
Understanding the expanded access process is the first step toward exploring whether this pathway might help in your situation. If you’re facing a serious disease or condition and standard treatments haven’t worked, talk with your treating physician about whether expanded access could be appropriate.
Additional resources are available through FDA’s expanded access web pages, manufacturer policy postings, and patient advocacy organizations focused on therapeutic innovation and early access to investigational therapies.
This information is educational and may not apply to every case. Decisions about investigational therapies should be made with a licensed treating clinician who understands your specific medical situation.