The answers to questions regarding when it is appropriate to request expanded access to investigational drugs for treatment use, when and how much a manufacturer may charge for an investigational drug under an expanded access request, and how new Form FDA 3926 can be used to apply for individual patient expanded access are the topics of three final guidance documents issue by the FDA.
Expanded access guidance. The guidance entitled “Expanded Access to Investigational Drugs for Treatment Use—Questions and Answers,” provides answers to questions concerning the implementation of the FDA’s regulations on expanded access to investigational drugs for treatment use (21 C.F.R. part 312, subpart I), which went into effect on October 13, 2009 (August, 13, 2009, 74 FR 40900) (Notice, 81 FR 35778, June 3, 2016).
Under the regulations, expanded access refers to the use of an investigational drug to diagnose, monitor, or treat a patient rather than to obtain clinical trial data. There are three categories of expanded access: (1) individual patient, including for emergency use; (2) intermediate-size patient populations; and (3) expanded access for widespread treatment use through a treatment investigational new drug (IND) or treatment protocol. The regulations are intended to facilitate the availability of INDs outside of a clinical investigation or approved drugs where availability is limited by a risk evaluation and mitigation strategy (REMS) to patients with serious or immediately life-threatening diseases or conditions who lack other therapeutic options.
Consistent with the goal of making expanded access processes more transparent, the FDA provided the guidance in a question and answer format to address questions about how the FDA is implementing its expanded access regulations, including questions about when it is appropriate to request expanded access under each of the three expanded access categories, the types and content of expanded access submissions, institutional review board review of individual patient expanded access, and the onset and duration of expanded access use.
In response to comments on the draft guidance (May 9, 2013, 78 FR 27115), the final guidance includes significant clarification on the three types of expanded access and when each type should be used.
Charging guidance. In 2009, the FDA amended the regulation concerning charging for investigational new drugs under an IND (74 FR 40872, August 13, 2009). The Final rule, which went into effect on October 13, 2009, created 21 C.F.R. sec. 312.8. The new guidance, entitled “Charging for Investigational Drugs Under an IND—Questions and Answers,” clarifies the requirements set forth in section 312.8. Specifically, it provides guidance on the circumstances in which charging for an investigational drug under an IND for the purpose of clinical trials is appropriate and also sets forth criteria for charging for an investigational drug for the three types of expanded access for treatment use and clarifies what costs can be recovered for an investigational drug (Notice, 81 FR 35779, June 3, 2016).
The FDA received several comments on the draft guidance (May 9, 2013, 78 FR 27116). Based on those comments, the major changes made to the guidance include adding clarification about charging for certain administrative costs in individual patient expanded access INDs and protocols, and the timing for submitting a request to the FDA to reauthorize charging.
Individual expanded access application guidance. The guidance entitled “Individual Patient Expanded Access Applications: Form FDA 3926,” describes Form FDA 3926 (Individual Patient Expanded Access—Investigational New Drug Application (IND)), which is available for licensed physicians to use for expanded access requests for individual patient (including emergency use) INDs as a streamlined alternative to Form FDA 1571, and describes the process for submitting expanded access requests for individual patient INDs (Notice, 81 FR 35776, June 3, 2016).
Form FDA 1571 is currently used by sponsors for all types of IND submissions. However, the FDA is concerned that physicians requesting expanded access for an individual patient may have encountered difficulty in completing Form FDA 1571 and providing the associated documents because Form FDA 1571 is not tailored to requests for individual patient expanded access.
The FDA received several comments on the draft guidance (February 10, 2015, 80 FR 7318). Both the guidance and Form FDA 3926 were revised based on public comments. One notable change includes the ability to use Form FDA 3926 for subsequent submissions to an existing individual patient expanded access IND.
Additional analysis of expanded access. For an interesting analysis of expanded access, including: (1) the use of Form FDA 3926; (2) ethical concerns that pharmaceutical manufacturers should weigh before deciding to honor expanded access requests; and (3) the new role of mainstream media reports and social media campaigns in influencing expanded access participation by manufacturers, see Individual compassionate use: concerns for drug manufacturers considering participation, April 17, 2015.
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