Expanded Access of Investigational Drugs: The Experience of the Center of Drug Evaluation and Research Over a 10-Year Period

Abstract

Background The purpose of this study was to describe the experience of the Center of Drug Evaluation and Research (CDER) with expanded access of investigational drugs. Methods Multiple searches of CDER’s document tracking system were performed to identify the number, type, and indication for all expanded access requests over the 10-year time period of January 2005 through December 2014. An additional search was performed to identify all active commercial investigational drug development programs during that time period and whether or not the clinical program was placed on hold. The two searches were then cross-referenced to identify those commercial investigational drug development programs placed on clinical hold due to serious adverse events occurring within expanded access programs. Results CDER receives over 1000 applications for expanded access each year. The majority are for single patients, roughly evenly split between emergency and nonemergency use. The vast majority, 99.7%, are allowed to proceed. The incidence of clinical holds for all commercial investigational drug development programs is 7.9%, as compared to only 0.2% related to adverse events observed in patients receiving drug treatments under expanded access. Conclusions The expanded access program is viewed as a success from FDA’s perspective based on the large number of applications processed and allowed to proceed each year. However, the actual number of patients and their health care providers that desire drug treatments available under expanded access is not known. It is exceedingly rare for a serious adverse event under expanded access to affect the development program for that drug.

Impact of Expanded Access on FDA Regulatory Action and Product Labeling

“…The vast majority of these requests are for new single-patient INDs for emergency or nonemergency access to treatment. 1 FDA recognizes that expanded access to investigational drugs can play an important role in the treatment of patients with serious or life-threatening diseases or conditions. While FDA supports patient access to investigational drugs, enrollment in clinical trials is the preferred option for eligible patients wishing to gain access to investigational drugs.…”

“…In our previous reviews of the Center for Drug Evaluation and Research (CDER) experience with expanded access, we have shown that more than 1000 applications are received each year, more than 99% of the individual access requests are allowed to proceed, the median review time is 4 days for nonemergency requests and less than 24 hours for emergency, and that FDA requests changes in 11% of those allowed to proceed to ensure patient safety. 1,2 Moreover, it is extremely rare for serious adverse events or deaths that occur under expanded access to interrupt the development program for an investigational drug.…”

“…3 Prior analyses focused on the potential impact on drug development of adverse experiences under expanded access and this analysis focuses on the potential effect on marketing approval and labeling. 1,2 To address this concern, we reviewed all of the regulatory decisions, both negative and positive, and subsequent product labeling for those products approved by the Office of New Drugs (OND) in CDER since implementation of the Prescription Drug User Fee Act IV (PDUFA IV).…”

Overview of FDA’s Expanded Access Program for Investigational Drugs

“…A review of almost 11,000 expanded access requests over a 10-year period, however, demonstrated that only two drug development programs were placed on clinical hold due to adverse events observed in patients receiving expanded access, and even these were temporary. 10 Therefore, it is very rare for an adverse event occurring during expanded access to adversely affect drug development.…”

Early Access Provision for Innovative Medicinal Products in Oncology: Challenges and Opportunities

“…The EMA provides recommendations through the Committee for Medicinal Products for Human Use (CHMP) for “Compassionate Use” ( 2 ), which recognizes two situations of exceptional application of a non-licensed medicinal product to patients: those applicable for a cohort of patients as “Compassionate Use” and those for “Named Patient Use” ( 2 ) ( Table 1 ). The early access equivalent in the USA is known as “Expanded Access,” which can be granted for three types of investigational new drug (IND) use: (1) individual patient IND use; (2) limited use for an intermediate-size IND patient population; and (3) treatment IND for widespread use ( 4 , 7 ). Similarities and differences in regulatory and ethical challenges between EAP programs in Europe and the USA are illustrated in Table 1 .…”