FDA’s expanded access program facilitates availability of investigational drugs while protecting safety and avoiding interference with drug development.
This article originally was published in the Spring 2018 issue of In-House Defense Quarterly, a publication of DRI – The Voice of the Defense Bar, and is republished with permission.
"Right to Try" legislation, which enables terminally ill patients or patients with a "life threatening disease or condition" to seek access to investigative drugs with little to no oversight from the FDA, has been enacted in 38 states as of the end of 2017. A similar bill passed the U.S. Senate by unanimous consent on August 3, 2017, and other bills are under consideration in the House. Right to Try champions contend that the legislation protects the fundamental right of people to try to preserve their own lives and promises to reduce bureaucratic wait times and paperwork. Its opponents counter that the FDA already has an effective system in place, the expanded access program—sometimes called "compassionate use" or "preapproval access"—which helps patients gain access to investigational products; that Right to Try legislation is unlikely to persuade manufacturers to provide investigational drugs outside clinical trials; and that reducing FDA’s role could endanger patients and invite abuse.
This article reviews the existing regulatory program for terminally ill patients to access investigational drugs and the Right to Try initiative, and probes the legislation’s purposes, mechanics, and consequences. The article concludes that the recent reforms to the FDA’s expanded access program—which may themselves have been a response to the push for Right to Try legislation—may already have achieved the improvements that Right to Try legislation is capable of achieving. Nonetheless, because many people believe that the FDA’s current role encroaches (however minimally) on patients’ "fundamental right" to fight to save their lives, federal Right to Try legislation may well become law.
Regulatory Background
Section 505 of the Federal Food, Drug, and Cosmetic Act (FDCA) generally prohibits interstate distribution of any new drug unless the Secretary of Health and Human Services (HHS) and, by delegation, the FDA approve an application supported by substantial evidence of the drug’s safety and efficacy, or otherwise authorize use of the investigational drug through a clinical trial or expanded access program. See 21 U.S.C. §355(a), (b) and (d). After completing toxicity studies on animals, a drug manufacturer must submit an investigational new drug application (IND) to the FDA and successfully complete three phases of human clinical trials before submitting the IND for FDA approval. Phase I trials test the safety of the drug on 20–80 healthy volunteers and last for several months. Phase II trials assess the drug’s safety and efficacy on a few dozen to hundreds of volunteers with the target disease or condition and last several months to two years. Phase III trials gather more information on safety and efficacy, based on the experiences of several hundreds to thousands of volunteers with the target disease or condition, and last one to four years. Of the compounds that enter Phase I, only 9.6 percent are ultimately approved for marketing. See U.S. Government Accountability Office, Investigational New Drugs: FDA Has Taken Steps to Improve the Expanded Access Program but Should Further Clarify How Adverse Events Data Are Used, at 5–7 (July 2017) [hereinafter GAO Report].
On different occasions, seriously ill patients have brought lawsuits to curtail the FDA’s authority to bar their access to investigational drugs. For example, in 1975, terminally ill cancer patients and their spouses brought an action to enjoin the government from interfering with the interstate shipment and sale of the unapproved drug Laetrile. United States v. Rutherford, 442 U.S. 544 (1979). The Supreme Court rejected the claim, noting that the FDCA makes no special provision or exception for drugs to treat terminally ill patients. Further, the Court held that "effective" does not necessarily denote a capacity to cure, and a drug can be unsafe for terminally ill patients if its potential for inflicting harm is not offset by the possibility of therapeutic benefit. Id. at 551–57; see also Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 495 F.3d 695 (D.C. Cir. 2007) (finding no constitutional right of access to experimental drugs).
FDA’s Expanded Access Program
While the FDA was successful in defending court challenges to its restriction of drugs to terminally ill patients, the agency created an exception during the AIDS epidemic. In the 1980s, AIDS spread rapidly; in 1987, only 15 percent of those diagnosed with the disease were left alive after five years. Gina Kolata, 15 percent of People With AIDS Survive 5 Years, NY Times, Nov. 19, 1987. The ruthless disease caused alarm and desperation in part because of the length of time required to bring a drug to market and because of the lack of access to experimental drugs. See Christina Corieri, Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of Their Treatment, Goldwater Institute Policy Report No. 266, 8 (Feb. 11, 2014) [hereinafter Goldwater Policy Report]. Against this backdrop, public pressure spurred the FDA in 1987 to develop formalized programs allowing patients to access investigational new drugs.
FDA’s expanded access program facilitates availability of investigational drugs while protecting safety and avoiding interference with drug development. U.S. Food & Drug Admin., Expanded Access to Investigational Drugs for Treatment Use – Questions and Answers: Guidance for Industry, at 2–3 (Oct. 2017) [hereinafter FDA Q&A]. Under FDA regulations, expanded access may be sought for (1) individual patients, including for emergency use; (2) intermediate-size patient populations; and (3) widespread treatment through an IND or treatment protocol. See 21 CFR 312.310, 21 CFR 312.315 and 21 CFR 312.320, respectively. Almost 96 percent of requests are for single patients; however, because intermediate-size and treatment requests grant access to groups of patients, more patients may have gained expanded access through these types of requests. GAO Report at 17. For each category, expanded access may be sought through an additional protocol in an existing IND or a new IND submission, and expanded access protocols may only be used if the sponsor of the existing IND (typically a commercial entity developing the drug for marketing) is also the sponsor of the expanded access. When the IND sponsor declines to sponsor the expanded access, a new expanded access IND must be submitted by a licensed physician. In the past few years, the FDA has revised the program, most significantly by drastically reducing the time necessary to complete an individual application.
Currently, the expanded access program has flexibility in processing time. If a patient must be treated within a limited number of hours or days, a sponsor may request and receive authorization for emergency access by telephone. From fiscal years 2012 to 2015, the FDA’s median response time on the more than 2,300 emergency expanded access IND requests that were submitted was less than one day. GAO Report at 19. In these cases, the sponsor must submit a new written IND within 15 working days of the authorization. Where expanded access is sought via an individual or an intermediate-size patient population expanded access protocol (rather than an IND), treatment can begin as soon as the submission is made. In all other cases, treatment may begin thirty days after the date the FDA receives the early-access application, unless the FDA gives earlier permission or the IND is put on clinical hold. From 2012 to 2015, the FDA took a median of between three and nineteen days to review individual (non-emergency) IND requests and thirty days to review intermediate-size and treatment IND requests. Id. at 20.
Expanded access for all categories may be available only if all of the following conditions are met:
- The drug sponsor agrees to the use.
- The investigators treating a patient or patients...
