Publication
Article
FDA Allows Access to Lifesaving Investigational Drugs
Compassionate use bridges gap between safety and patients' immediate need for biologics, devices, drugs, devices on spearhead of research and development.
Imagine the anguish, disappointment, and frustration of a patient and family members who hear or read about a promising new medication under study for a disorder, but the patient does not meet the sometimes-intricate qualification criteria to be enrolled in a clinical trial of the proposed product. It could also be that the patient does not have access to a practitioner who is connected to the appropriate resources or has a practitioner who is unfamiliar with participation requirements for such clinical trials. Based on an unfulfilled need, the FDA developed a program to facilitate patient access to investigational medications when certain criteria exist.
The FDA Expanded Access (EA) program, commonly known as compassionate use, exists to bridge the gap between exceptional levels of patient safety achieved by the agency’s thorough review and approval processes1 and patients’ immediate urgent need for lifesaving biologics, drugs, and medical devices on the spearhead of research and development. Fundamentally, the implementation and regulation of EA differs from that of clinical trials by intent, the former being treatment of the patient and the latter being research.2 Since the program’s inception in 1987,3,4 the mission of the EA program has been to regulate and connect physicians with manufacturers on behalf of patients to provide investigational treatments in circumstances in which approved therapy options have been exhausted. From fiscal years 2015 to 2019, 8385 patients were accepted to receive investigational drugs and biologics through EU, at an approval rate of more than 90%.2
Patients must meet 3 general requirements to qualify for EA: They have a serious or immediately life-threatening condition for which there is no satisfactory alternative therapy, they have exhausted approved therapies and are unable to participate in available clinical trials, and the potential risks from the drug must not exceed that from the condition or disease.5,6
If these expectations are met, physicians may begin the process of submitting an individual patient investigational new drug application to the FDA. Prior to submission, the physician must obtain authorization from the manufacturer for using the investigational product, consult the relevant institutional review board for approval, obtain informed consent from the patient, and submit various forms to the FDA, depending on the patient’s emergent status.7
Even when a patient meets the FDA’s 3 general requirements for EA, manufacturers retain their autonomy in the provision of investigational therapies. If a manufacturer determines the use of a particular investigational drug or biologic interferes with its development process, the FDA cannot mandate that the manufacturer provide a product.4 Pharmaceutical companies are not required to provide EA to investigational drugs at all, and some expressly forbid it.4
It is the responsibility of the physician and supporting staff members to communicate and negotiate with manufacturers; however, resources exist to assist in the process. The Reagan-Udall Foundation for the FDA provides a centralized repository of EA program information for companies, patients, and providers to reference, as well as a directory of EA-participating manufacturers for use by providers.8 In September 2020, the Reagan-Udall Foundation launched the EA eRequest, a user-friendly application portal for physicians to submit EA applications completely online.9,10 This complements the FDA’s recent efforts to streamline the EA application process, reduce turnaround time, and simplify the process for patients and providers.4
Although the EA investigational new drug process is manufacturer- and physician-driven, it is important for pharmacists to maintain awareness of the EA program and to participate in it as a member of the health care team.
As drug therapy experts, pharmacists are uniquely equipped to provide physicians with information and suggestions concerning promising investigational drugs in clinical research, which could benefit mutual patients.
As the most accessible health care providers,11 pharmacists educated about EA can effectively counsel patients on what actions they can and cannot take in coordination with their physicians to participate in EA.
Pharmacists can also direct patients exploring EA as a potential course of action in their treatment plans to official educational resources through the FDA and the Reagan-Udall Foundation. Ensuring that patients are aware of their potential treatment options can be critical in cases meeting EA criteria and could mean the difference between optimal and suboptimal patient outcomes.
It would not be unusual for patients to vent their frustrations with the federal government and its medication regulatory schemes with pharmacists. Indeed, pharmacists often hear such comments from patients about access to medications and other patient frustrations with the nation’s health care system when facing such challenges. Access challenges may be exacerbated for patients who do not live near academic health centers where practitioners have encountered the EA program before and have the staff support to pursue that avenue to facilitate patient access to these investigational medications.
References
1. Development & approval process: drugs. FDA. Updated August 8, 2022. Accessed November 29, 2022. https://www.fda.gov/drugs/development-approval-process-drugs
2. Overview of expanded access (EA) program and EA eRequest site. FDA. Updated January 26, 2022. Accessed November 29, 2022. https://www.fda.gov/about-fda/fda-pharmacy-student-experi-ential-program/overview-expanded-access-ea-program-and-ea-erequest-site
3. Subpart I - expanded access to investigational drugs for treatment use. National Archives Code of Federal Regulations. Updated November 25, 2022. Accessed November 29, 2022. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-I
4. Expanded access program report. FDA. May 2018. Accessed November 29, 2022. https://www.fda.gov/media/119971/download
5. Expanded access. FDA. Updated November 28, 2022. Accessed November 29, 2022. https://www.fda.gov/news-events/pub-lic-health-focus/expanded-access
6. Transcript: expanded access part 1: introduction (May 2019). FDA. Updated May 24, 2019. Accessed November 29, 2022. https://www.fda.gov/drugs/fda-drug-info-rounds-video/transcript-expanded-access-part-1-introduction-may-2019
7. Transcript: expanded access part 2: how to submit a single patient IND (September 2019). Updated September 16, 2019. Accessed November 29, 2022. FDA. https://www.fda.gov/drugs/fda-drug-info-rounds-video/transcript-expanded-access-part-2-how-submit-single-patient-ind-september-2019
8. Company directory. Reagan-Udall Foundation. Accessed November 29, 2022. https://www.reaganudall.org/company-directory
9. Expanded access navigator. Reagan-Udall Foundation. Accessed November 29, 2022. https://navigator.reaganudall.org/
10. New expanded access eRequest app allows physicians to submit EA requests online. News release. Reagan-Udall Foundation for the FDA. September 23, 2020. Accessed November 29, 2022. https://reaganudall.org/news-and-events/announcements/new-expanded-access-erequest-app-allows-physicians-submit-ea-requests
11. Crossley K. Public perceives pharmacists to be some of the most trusted professionals. Pharmacy Times®. March 18, 2019. Accessed November 29, 2022. https://www.pharmacytimes.com/view/public-perceives-pharmacists-as-some-of-the-most-trusted-professionals
About the Authors
Joshua D. Melson is a PharmD candidate at the University of Kentucky (UK) College of Pharmacy and an MBA candidate at the UK Gatton College of Business and Economics, both in Lexington.
Joseph L. Fink III, JD, Dsc (Hon), BSPharm, FAPHA, is professor emeritus of pharmacy law and policy at the University of Kentucky College of Pharmacy in Lexington.
