Expanded Access - FDA Regulations

FDA Regulations

Since 1987, the FDA has had rules in place that have enabled patients, under specific circumstances, to access drugs or biologics that are still in development for treatment purposes. These expanded access program rules were amended in 2009 by the FDA to ensure “broad and equitable access to investigational drugs for treatment.”

The regulations include the following:

• Criteria that must be met in order to authorize the expanded access use
• Requirements for expanded access submissions
• Safeguards to protect patients and the clinical trial process

The regulations also include general criteria for granting expanded access:

• The patient must have a serious condition or disease for which there is no comparable alternative therapy available
• The patient must be unable to participate in a clinical trial
• The potential benefit must outweigh the potential risk of using the treatment
• There should be no impact on the completion of the clinical trial or the drug’s approval

Despite the updated regulations, debate remains over key elements of expanded access:

• Deciding at what point in the clinical trial process access should be given. Some stakeholders support expanded access programs after phase I testing in clinical trials, which establishes the drug’s safety. The FDA, however, believes that most drugs should not be eligible until some point during phase III when efficacy data have been obtained, unless compelling phase II data on safety and efficacy are available.
• Weighing risks to the patient against the potential benefits. The FDA requires that a physician and an institutional review board (IRB) determine that a treatment will not pose undue risk to the patient, relative to the condition he or she is suffering from. However, the FDA maintains the right to overrule the physician and IRB.
• Determining who should get access. The FDA states that expanded access should only be considered for patients with a serious disease or condition, but the FDA’s rules do not provide a definition of “serious”; instead it provides examples of diseases and conditions that fall into this category. In the case of a cancer drug, the sponsor of an expanded access program must define exactly which patients will get access. Most often, access is limited to those patients with the same type of cancer the drug is being tested for.

A number of challenges can exist when patients seek access to investigational drugs:

• Obtaining an IRB review. Finding time on an IRB’s schedule can be difficult, particularly for doctors who are not based at research centers where IRBs are readily available. The fee for the review may pose a problem as well. It may be unclear who is responsible for the cost of the IRB review, which can be as much as $2,000. Many IRBs conduct reviews pro bono but others that charge will often only waive their fees for research done in their hospital.
• Protecting physicians against liability risk. Currently, physicians may be concerned that they could face a liability risk for investigational drugs that they recommend to patients or help them gain access to, potentially discouraging them from doing so. The FDA does not have jurisdiction over this issue but there is a bill in Congress, the Compassionate Access Act of 2010 (H.R. 4732), that would address the situation.
• Paying for the drug. While the FDA allows drug companies to recover the costs of providing a treatment through an EAP, many companies may hesitate to do so because it requires disclosing the cost of their drug, which is often a closely guarded secret. In addition, many insurance companies won’t cover the costs of experimental treatment so access could be limited to patients with the means to pay for it.
• Assessing the potential impact of adverse events on drug development. Adverse events (AEs) that result from expanded access programs must be reported to the FDA in the same way AEs are reported in the case of a clinical trial. The FDA states that, to their knowledge, no drug candidate has been turned down for approval because of an adverse event that appeared in an expanded access program.