The possibility that an investigational drug, not yet approved for commercial use, could be life-saving to some patients has been an ongoing dilemma for industry and for healthcare providers (HCPs). On the one hand, desperate patients, sensing that such a drug might be available, plead their case to regulators and to the drug developer; on the other, the entire FDA approval process is designed to minimize use of drugs that might have high risks or be ineffective. Nevertheless, the practice of what is called “compassionate use” (FDA prefers the term “expanded access”) has been regulated at least since 2009, when FDA issued revised guidelines (21 CFR Part 312, subpart 1) to formalize the application process.
Now, the agency has issued a revision of that, centered on a document (Form 3926) that HCPs are to use when seeking access to the drug. As was the case previously, the regulations and procedures recognize three situations:
- when emergency use is sought for an “immediate, life-threatening disease or condition” for an individual patient
- when a small number of patients (generally of the scale of an intermediate clinical trail; FDA does not specify the number) seek the drug
- when “widespread” treatment is sought.
Generally speaking, the FDA guidelines seek to steer the second and third categories into an existing clinical trial, and to ensure that the admission process does not interfere with the conduct of the actual trial (and there are mechanisms, such as open-label trails for late-stage development, to accommodate larger patient populations, as well as the variety of accelerated or fast-track drug-approval protocols currently in use).
The expanded access guideline allows for a sped-up approval process for individual patients and emergency use; the physician files the form and can call FDA for permission to proceed. In less dire situations, the physician is to file with an institutional review board (IRB) and expect a response within 15 days. The clinical investigators are to be part of the approval process.
All of these steps, however, depend on the voluntary participation of the drug developer. A drug might be in extremely limited supply during an early-stage trial; the developer might have concerns that an unfavorable outcome could influence the trial’s progress; and the risks of adverse events, toxicity or other risk factors might outweigh the potential value of the therapy. FDA is now providing both instructions for the Form 3926 application; an FAQ for the overall process, and a guideline for pricing the drug when used in an expanded access setting—and on that point, FDA, starting from the perspective of ensuring that the pricing doesn’t interfere with the clinical trial’s progress, says that only costs directly attributable to making the drug available can be charged.