Regulatory Focus™ > News Articles > New FDA Draft Guidance Aims to Clarify Compassionate Use Process

New FDA Draft Guidance Aims to Clarify Compassionate Use Process

Posted 09 May 2013 | By Alexander Gaffney, RAC

A new draft guidance document released by the US Food and Drug Administration (FDA) aims to clarify details regarding so-called "expanded access" to pharmaceutical therapies that are currently being evaluated under an approved investigational new drug application (IND).


Under current FDA regulations, sponsors must obtain approval from FDA for their IND before beginning a clinical trial. That IND is essentially a license to be exempt from the Federal Food, Drug and Cosmetic Act (FD&C Act), which otherwise prevents an unapproved drug product from entering into interstate commerce.

Under the terms of that IND, sponsors are supposed to tightly limit and monitor the patients who come into contact with the drug, primarily under a clinical trial.

But over the last two decades, FDA has moved to allow sponsors to expand access to their products, more commonly known as a "compassionate use exemption," with the intent of allowing those patients who have the most to gain and the least to lose to access an investigational product.

The compassionate use exemption has increased dramatically in recent years, according to a 2012 report in the Wall Street Journal. In 2010, for example, the program saw around 1,000 patients. A year later, that number increased to 1,200.

However, companies and regulators alike have expressed some hesitancies about the program. For companies, expanded access means letting products out of tightly controlled and heavily monitored environments, potentially subjecting the product to incorrect use and previously-unknown adverse events, which would still need to be reported to FDA. Such incidents could potentially raise questions for regulators, thereby harming the chance of a product getting to market. Further, some companies have expressed their fears about expanded access programs robbing their clinical trials of some patients, which could reduce the statistical validity of a trial and potentially harm other patients by delaying a drug's path to market.

Regulators, too, are still wary of the program. "There's this sense from patients that these are miracle drugs," said Richard Klein, director of FDA's Office of Special Health Issues, to the Wall Street Journal in October 2012. Even if the drug works-which is far from certain in early-stage clinical trials-the benefit might not amount to much.

Existing Guidance

FDA has already released some guidance on the expanded access program, noting the various requirements that must be followed during the course of the program. Most important of all may be accounting for the risks to the patient. The proposed use must still be approved by an Institutional Review Board (IRB) and the patient or guardian is required to sign an informed consent form.

In addition, FDA's prior guidance makes clear that not every patient will be eligible for the program.

"In order for a patient to gain access to an investigational drug outside of a clinical trial, the patient must have a serious or immediately life-threatening disease or condition and no comparable or satisfactory therapeutic alternatives," FDA explained. "Additionally, the drug manufacturer and the patient's doctor must make special arrangements to obtain the drug for the patient," which must in turn be authorized by FDA "to avoid exposing patients to unnecessary risks."

Those arrangements can also extend beyond a single patient and into intermediate-sized and large patient populations with the same risk profile.

Such arrangements are optional for companies, though in recent years some patients have turned to the Internet to obtain wider support for their compassionate use petitions to companies in an attempt to obtain their cooperation, either willing or coerced by publicity.

New Guidance

Now FDA is out with additional guidance meant to clarify a few additional aspects for companies by answering some of the most common questions presented to FDA.

The guidance answers many of the more practical aspects of the expanded use process, including:

  • how to obtain clearance (through a protocol amendment to the IND submission or a new IND submission)
  • the information that must be contained within the protocol amendment or new IND (similar to the IND, though with details specific to the expanded access request)
  • the eight different sub-categories of expanded access submissions (individual patient IND, individual patient protocol, emergency IND, emergency protocol, intermediate-size patient population IND, intermediate-size patient population protocol, treatment IND, and treatment protocol)
  • who can request the expanded access (The IND sponsor, which in some cases can be the patient's physician)
  • the role of the patient's physician in determining the patient's need and suitability for expanded access
  • FDA's reasons to deny an expanded access IND (unacceptable risk, mostly)
  • the approval of multiple courses of treatment if the patient suffers from a chronic condition (FDA may authorize a specific duration of treatment, after which another request would be required)
  • whether full IRB approval is required for each patient (Yes, though FDA is aware of concerns about the burdensome hurdle this poses to expanded access and is willing to consider "other options" in the future)
  • the use of "emergency" patient access procedures under 21 CFR 312.310(d)
  • the use of intermediate-size patient population access programs ("When multiple patients with the same disease or condition seek access to a particular drug … FDA believes that it is generally most efficient to consolidate access in a single … protocol.")
  • how FDA determines that an expanded access protocol won't interfere with an ongoing clinical trial (generally predicated on the scope of expanded access relative to the number of enrolled patients in the trial)
  • whether FDA may determine, on its own, that a drug needs an expanded access protocol (Yes)
  • whether FDA may require a company to provide expanded access to a drug (No)

The full guidance may be found here. Comments will be accepted by FDA until 8 July 2013, and may be submitted here.

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