“Expanded Access,” is a regulatory pathway for physicians to gain access to experimental therapies for patients who usually do not qualify for the clinical trial. This pathway often represents one final chance against a condition that is severely debilitating and/or fatal. Often called “Compassionate Use,” the number of patients and physicians requesting access to experimental therapies has been growing steadily over the past three decades.
Expanded access/compassionate use began in the early 1980s with HIV/AIDS. In 2001, the advocacy group Abigail Alliance was formed by the clinician and family of 21-year-old cancer patient Abigail Burroughs, who lobbied to gain access to the (then) experimental drug Erbitux. In recent years, social media campaigns, such as the 2014 Josh Hardy-Chimerix case, have been used to pressure pharmaceutical companies to grant access to experimental therapies.1
This past year, the Expanded Access pathway became a little smoother: The FDA created a specific and simpler form (No. 3926) for physicians to use in applying for expanded access, and Subtitle D of the 21st Century Cures Act, which became law in December, requires pharmaceutical companies to have publicly accessible Compassionate Use policies.
As access to experimental agents becomes somewhat simpler for patients, the delivery of the agents becomes more challenging, as these experimental therapies are increasingly cell based therapies. As an entity that specializes in cell therapy clinical trial logistics, we want to give readers a look at some of the challenges in delivering a dose or doses of a biologically active therapy to patients who are granted compassionate use status.
Expanded access essentially represents a clinical trial of one, and the FDA must approve the physician’s application and issue a single use Individual New Drug (IND) number. The Institutional Review Board (IRB) at the hospital where the treatment will be administered must also review and approve the treatment. Contrary to the common notion that it is the FDA that stands between patient and therapy, the FDA approves 99 percent of the applications. However, although the FDA may approve the treatment, the pharmaceutical company that owns the experimental agent is under no obligation to provide it, nor is the patient’s insurer obligated to cover the cost.
The drug manufacturer may resist providing the drug for a number of reasons. They have invested millions of dollars in drug development, and fear the public reaction (including stock price), possible regulatory scrutiny, and other potential problems if the patient suffers a negative outcome. In addition, supplies of experimental agents can be extremely limited and/or very costly. And being held hostage to a social media campaign is not conducive to rigorous drug development. Yet companies often allow use, although there is no way of knowing how often such requests are turned down.
The next step is to dispense the agent, and as the entity that packages, labels, and ships the agent to the patient, we are only executing the final lap in a relay race. We know that the patient’s physician, family, staff members at the FDA, members of the Institutional Review Board, pharmaceutical company employees, and many others have already given their time and expertise to grant a patient access to the treatment. Even so, the final lap is highly regulated, can be complex, and there is no room for error.
Fisher BioServices must receive permission from the drug owner, as well as the IND number, to ship the therapy to the patient. If the agent is already packaged for patient use, we can ship according to the existing general instructions. However, if patient-specific packaging and labeling is required, every step in this process must follow an approved, written, standardized instruction called a batch record; the completion of the steps is documented as they are performed. The printing of the label, the match between ID, IND and other numbers, is checked and double-checked.
The majority of cell therapies require specific temperature management, so the equipment needed for maintaining the agent at the correct temperature must be prepared in advance. These include special sleeves embedded in dry ice for handling therapies at ultra cold storage temperatures, or preparing a CryoCart with liquid nitrogen for labeling and handling cryogenically frozen agents. Labeling and packaging doses of experimental drug for patients may have to be performed on a dedicated assembly line, and the set-up and completion of this one-dose assembly line is also documented, per regulations.
Cryogenically frozen therapies must be shipped in a liquid nitrogen dry shipper that requires 48 hours of charging, or freezing, time before the therapy can be placed inside for shipment. Once it has shipped, our pharmacy staff will follow up with the clinical site pharmacist, to verify that the agent arrived on time and in the appropriate condition for administration to the patient.
We are proud of our staff, as every time we receive a request to provide an agent under expanded access—including a rush request for a severely ill patient—everyone involved gladly accepts the extra tasks and demands, and works hard to get it done. Contact us using the link below if you'd like to learn more about cell therapy distribution and how our services provide expert management of these critical biological materials.
Hogan, M. (2016). (R)evolution: Toward a new paradigm of policy and patient advocacy for expanded access to experimental treatments. BMC Medicine, Vol. 14. DOI: 10.1186/s12916-016-0586-6