How does FDA determine if a drug should be approved for compassionate use?

As part of The 21st Century Cures Act, FDA is required to consider additional mechanisms to expedite access to new drugs, including those currently under investigation. In fact, the 21st Century Cure Act mandates that pharmaceutical manufacturers have to post their policies on expanded access (a.k.a. “compassionate use”) for investigational drugs by: (1) the first initiation of a Phase 2 or Phase 3 study or (2) within 15 days after the drug receives a fast track, breakthrough, or regenerative advanced therapy designation.

What is expanded access? An FDA guidance document published this month defines it as follows:

Expanded access refers to the use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition rather than to obtain the kind of information about the drug that is generally derived from clinical trials…a patient cannot receive an investigational drug through the expanded access pathway unless the sponsor of the investigational drug agrees to provide such access.

Expanded access is often known by the terms “compassionate use” and “preapproval access”. FDA further explains the distinction between expanded access and standard drug approvals as follows:

The main distinction between expanded access and the use of an investigational drug in the usual studies covered under an IND is that expanded access uses are not primarily intended to obtain information about the safety or effectiveness of a drug. Expanded access, access, and treatment use may also refer to (1) use in situations when a drug has been withdrawn for safety reasons but there exists a patient population for whom the benefits of the withdrawn drug continue to outweigh the risks; (2) use of a similar, but unapproved drug (e.g., foreign-approved drug product) to provide treatment during a drug shortage of the approved drug; (3) use of an approved drug where availability is limited by a risk evaluation and mitigation strategy (REMS) for diagnostic, monitoring, or treatment purposes by patients who cannot obtain the drug under the REMS; or (4) use for other reasons.

Expanded access regulatory submissions come in two forms:

Expanded access protocol submitted as a protocol amendment to an existing IND. This approach can only be used if the pharmaceutical manufacturer is seeking expanded access for a product that already has an existing IND New IND submission. This submission must be separate and distinct from any existing INDs and is intended only to make a drug available for treatment use under expanded access. Oftentimes this is applied for individual patient use when a patient’s physician believes the drug would work for an individual patient.

FDA has three categories of drugs that could potentially qualify for expanded access of an investigational drug.

Individual patients. These are given on a case-by-case basis.Intermediate-size patient populations. These typically smaller than full indication population and requires a treatment protocol alongside an existing Investigational New Drug Application (IND) by. Large population. This involves expanded access for widespread treatment use through a treatment IND or treatment protocol

More detail on the information required to make an expanded access submission under each of these categories, relevant governmental forms, IRB approval and informed consent considerations, and more detail is available in the FDA Guidance document on Expanded Access.