When proposing an expanded access IND application for treatment of groups (or populations) of patients, an applicant should ensure that their proposal meets the criteria for expanded access applications described in the Expanded Access IND Application: Overview. As mentioned elsewhere in this module, FDA regulations allow access to investigational drugs for treatment purposes for two categories of groups of patients:
intermediate-size patient populations (n >1), and
larger populations for use of the drug under a treatment protocol or treatment IND application
An IND application intended for treatment of an intermediate-size patient population should be clearly identified as “Expanded Access Submission- IND Application for Intermediate-Size Population”. An IND application intended for treatment of a large-size population (i.e. widespread treatment use) should be clearly identified as “Expanded Access Submission-Treatment IND Application”. An applicable box in Section 12 on Form FDA 1571 (PDF - 830KB) should be checked in each case. The suggested format for expanded access IND applications intended to treat populations of patients may be found in Expanded Access IND Application: Contents and Format.
Sponsors of expanded access IND applications have the same Investigators’ Responsibilities as sponsors of IND applications intended for clinical investigations. The procedures for safety, annual, and other IND Application Reporting for expanded access IND applications are similar to those for investigational IND applications. The requirements for mandatory IND Application Safety Reporting are the same as for all other IND applications.
Additional considerations for IND applications intended for treatment of patient populations are discussed below.
IND applications for intermediate-size patient populations
FDA may ask sponsors of multiple applications to consolidate expanded access under one application when the agency has received a significant number of requests for individual patient expanded access to an investigational drug for the same use.
Submission of an expanded access IND application for a group of patients would be appropriate in any of the following situations:
The intended investigational drug is not being developed. The drug is not being developed, for example, because the disease or condition is so rare that the sponsor is unable to recruit patients for a clinical trial.
The intended investigational drug is being developed and studied in a clinical trial, but patients requesting the drug for expanded access use are unable to participate in the trial. For example, patients may not be able to participate in the trial because they have a different disease or stage of disease than the one being studied or otherwise do not meet the enrollment criteria, because enrollment in the trial is closed, or because the trial site is not geographically accessible.
The intended investigational drug is an approved drug product that is no longer marketed for safety reasons or is unavailable through marketing due to failure to meet the conditions of the approved application.
The intended investigational drug contains the same active moiety as an approved drug product that is unavailable through marketing due to failure to meet the conditions of the approved application or a drug shortage.
In general, upon review of annual reports for an expanded access IND application for an intermediate-size population, FDA will determine whether it is appropriate for the expanded access to continue. FDA may ask the sponsor to conduct a clinical study or, if the number of patients enrolled increases, to submit an IND application for larger population widespread treatment use.
IND applications for widespread treatment use (Treatment IND applications)
If an investigational drug is considered for widespread treatment use, in addition to the requirements applicable to any expanded access IND application (see Overview, Contents and Format, Reporting, Investigators’ Responsibilities), the following conditions must be met:
the drug must be investigated in a controlled clinical trial under an IND application designed to support a marketing application for the expanded access use or all clinical trials of the drug have been completed, and
the sponsor of the IND application supporting marketing must be actively pursuing marketing approval of the drug for the expanded access use with due diligence, and
there must be sufficient clinical evidence of safety and effectiveness to support the expanded access use.
Note: For a serious disease or condition, such supportive evidence would ordinarily consist of data from phase 3 trials, but could consist of compelling data from completed phase 2 trials. For an immediately life-threatening disease or condition, such supportive evidence should include all available scientific evidence to provide a reasonable basis to conclude that the investigational drug may be effective for the expanded access use and would not expose patients to an unreasonable and significant risk of illness or injury. This evidence would ordinarily consist of clinical data from phase 3 or phase 2 trials, but could be based on more preliminary clinical evidence.