The United States Food and Drug Administration (FDA) has recently issued guidance in response to a request in the 21st Century Cures Act, in an attempt to ease the procedural challenges doctors and patients must navigate when seeking access to investigational treatments. The Act called on the FDA to clarify key policy issues around expanded access to investigational drugs for individual patients with no other options.
The guidance provides information about the implementation of the FDA’s regulations on expanded access to investigational drugs for treatment use under an investigational new drug application (IND), which went into effect on October 13, 2009. This guidance is released in tandem with two other guidance documents, “Charging for Investigational Drugs Under an IND,” and “Individual Patient Expanded Access Applications: Form FDA 3926.”
Expanded Access to Investigational Drugs for Treatment Use
This guidance document focuses on expanded access, which is defined as the “use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition.” The document notes that the main distinction between expanded access and the use of an investigational drug is that expanded access uses are not primarily intended to obtain information about the safety or effectiveness of a drug. Further, expanded access to an investigational drug can only be provided under a treatment IND or protocol if the sponsor is actively pursuing, with due diligence, marketing approval of the drug for the expanded access use.
The guidance discussed the roles of the patient’s physician and FDA in determining if expanded access for an individual patient is appropriate as well, noting that the FDA may permit expanded access to a drug for an individual patient when the criteria in 21 CFR § 312.305(a) (applicable to all types of expanded access) and criteria in § 312.310(a) (specific to individual patient expanded access) are met.
Another questions focused on reasons for the FDA to deny a request for individual patient expanded access when previous requests for the same drug for the same or a similar use have been permitted. The FDA noted that each request for individual patient expanded access to a drug should be treated as a unique clinical situation and the risks and benefits should be evaluated based on that clinical situation, and that there may also be nonclinical reasons for denying expanded access.
The guidance document also delineates when an expanded access protocol submission should be used and when a new expanded access IND submission should be used, as well as how the FDA categorizes and subcategorizes expanded access submissions.
Charging for Investigational Drugs Under an IND
This guidance discussed the general time that the FDA has to review and respond to a request to charge for an investigational drug. While the regulations do not specify a time frame, the FDA stated that it intends to respond to charging requests within thirty days of receipt, “when possible.”
The document noted that once the FDA authorizes a request to charge, and that the FDA determines whether a sponsor may charge for an investigational drug used in a clinical trial or for expanded access, the FDA does not decide how that charging is to be carried out. The FDA anticipates that the sponsor will typically charge a patient directly or would charge a third-party payer if reimbursement were available.
The guidance document also discussed charging in clinical trials, charging for expanded access use, and cost recovery calculations.
Individual Patient Expanded Access Applications
This guidance document discussed several topics, including the procedures and timeline for processing form FDA 3926.
Non-Emergency Situation
In a non-emergency situation, once the FDA receives Form FDA 3926, the FDA will assign an individual IND number to the IND and will either allow the treatment use to proceed or put the application on clinical hold. The IND will go into effect either: (1) after the FDA notifies the physician or (2) thirty days after the FDA receives the completed form, if no notification occurs by that time.
Emergency Situation
If there is an emergency and authorization of the expanded access use is requested before a written submission can be made, the physician is required to explain how the expanded access use will meet the required criteria. In these situations, the FDA may authorize expanded use of the investigational drug and treatment may begin before the FDA receives the written submission. However, the physician must agree to submit an expanded access submission within fifteen working days of FDA’s authorization of the expanded access use.
If the treatment involves the emergency use of an investigational drug and approval from an IRB cannot be obtained before treatment, treatment can begin without prior IRB approval, as long as the IRB is notified of the emergency expanded access use within five working days of treatment.
Congressional Response
House Energy and Commerce Committee Chairman Fred Upton welcomed the action, noting, “We appreciate the agency taking these steps on the #Path2Cures and look forward to working with manufacturers, providers, patients, and their caregivers to continue to improve this process going forward.”