The US Food and Drug Administration (FDA) on Thursday finalized two question and answer guidance documents on charging for investigational drugs and expanded access for the compassionate use of investigational drugs for those with life-threatening diseases or conditions, as well as a new streamlined form for applying for expanded access.
The new form, known as the Form FDA 3926, is part of an expedited process to help patients gain access to drugs that are still in clinical trials, though as Richard Klein, director of the Patient Liaison Program at FDA told us late last month, the new form may not actually be all that much of a simplification.
Klein dispelled the myth that the new form will reduce the time it takes for doctors to apply for expanded access (a process that’s usually already confirmed between the company of the investigational drug and the physician applicant before reaching FDA) from 100 hours to one hour.
“Informally speaking to physicians who file the 1571 [the previous compassionate use form] suggest to me that the time to complete the request generally takes them less than an hour,” he told us. As for the new form, he said: “Our goal was to pull the appropriate fields out of the more complex and confusing form to make it easier and more straightforward for physicians unfamiliar with the regulatory paperwork to submit a treatment use application.”
The new form comes as FDA's nonprofit arm, the Reagan-Udall Foundation (RUF), is working to build an online navigator to help patients and physicians understand the compassionate use process better.
In terms of changes between the draft guidance on the Form FDA 3926, first announced in February 2015, FDA said Thursday: “Both the guidance and Form FDA 3926 were revised based on public comments and editorial changes were made primarily for clarification. One notable change includes the ability to use Form FDA 3926 for subsequent submissions to an existing individual patient expanded access IND.”
As for both the finalized question and answer documents, which were first proposed in draft form in 2013, in addition to editorial changes made primarily for clarification, the final guidance on compassionate use includes “significant clarification on the types of expanded access and when each type should be used,” and for the cost Q&A, “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 FDA to reauthorize charging,” FDA said.
FDA Commissioner Robert Califf said in a statement on Thursday: “One way we hope to make things simpler for physicians is to reduce the amount of time they spend filling out a request for access to an investigational drug.”
The release of the finalized documents comes as new state legislation, which has passed in 28 states, is meant to skirt around FDA’s compassionate use process and allow access to investigational drugs more quickly, though it’s unclear if any physicians have actually been able to use such legislation to provide access to new treatments for patients.
The final Q&A on companies charging for investigational drugs notes that FDA intends to respond to charging requests “within 30 days of receipt when possible.” FDA also notes that companies can preserve the blinding in certain clinical trials and still charge patients.
“We are not providing hypothetical examples because we anticipate that the method for preserving the blind will be unique to each study design,” FDA said.
What to Charge
As far as how much companies can charge, FDA makes clear: “A sponsor can only recover the direct costs of making a drug available to subjects in a clinical trial — that is, those costs that are specifically and exclusively attributable to providing the drug to clinical trial subjects (21 CFR 312.8(d)(1)). These include costs to manufacture the drug in the quantity needed to conduct the clinical trial for which charging has been authorized or costs to acquire the drug from another source, including costs to ship and handle (e.g., store) the drug.”
For individual patient expanded access, the sponsor may not charge for indirect costs, including administrative costs associated with providing an investigational drug.
“Examples of indirect costs include:
- Costs associated with developing the treatment protocol and informed consent document;
- Costs associated with corresponding with the institutional review board (IRB), FDA, and/or the drug manufacturer;
- Costs associated with reporting to the IRB and/or FDA;
- IRB fees and expenses.
When charging for an investigational drug used in an intermediate-size patient population expanded access IND or protocol (under § 312.315) or a treatment IND or protocol (under § 312.320), FDA notes that “in addition to the direct drug costs, a sponsor may recover the cost of (1) monitoring the expanded access IND or protocol, (2) complying with IND reporting requirements, and (3) other administrative costs directly associated with the expanded access use.”
The more general Q&A on expanded access also gives a detailed breakdown on the basics of expanded access, or what was previously known as compassionate use, the forms used, who can make a submission (sponsor of an IND or a licensed physician), why expanded access might be denied and other situations, including emergencies.
Charging for Investigational Drugs Under an IND — Questions and Answers Guidance for Industry
Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers Guidance for Industry
Individual Patient Expanded Access Applications: Form FDA 3926 Guidance for Industry