Cultivating Innovation in Precision Medicine Through Regulatory Flexibility at the FDA

Abstract

Medical researchers perpetually aspire to a future where an individual’s genes will chart the way for the identification and prescription of the right lifesaving drug. The drug will be tailored to a patient’s specific genetic profile, assuring that the drug will work safely and effectively for that patient. During the course of care, a physician will extract a biological sample from the patient, run it through a diagnostic test, and the test results, along with the patient’s medical history, will guide the medical decision on which drug to prescribe. Such an integrative process eliminates the potential for that patient to experience devastating adverse drug events because the drug is not safe for them or receive ineffective (and assuredly expensive) treatment because the drug is not working for them. Such a future provides benefits not only to the patient but also to countless entities and actors within the public health and medical enterprise.

This scenario may be coming closer to fruition as research initiatives and public support for the field of precision medicine gain momentum. The National Institutes of Health (NIH) describes precision medicine as "an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person." President Obama initially channeled $215 million into the Precision Medicine Initiative (PMI), with funds to the NIH and the Food and Drug Administration (FDA) “to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.” In remarks at the White House East Room, Obama touted precision medicine as "delivering the right treatments at the right time, every time to the right person.” The 21st Century Cures Act, signed into law on December 13, 2016 further supports the PMI and related research with a $4.8 billion pledge over the next ten years.

The push for precision in the drug context is not new. The PMI and the field of precision medicine build on decades of genomic research and the successful sequencing of the human genome. Many terms have evolved to describe the concept of harnessing genomic information to guide the development of diagnostics and treatment for individuals or subpopulations of patients: pharmacogenomics, personalized medicine, targeted medicine, and most recently, precision medicine. The PMI emphasizes the need for collaborations of academic medical centers, researchers, patients and patient advocates, private foundations, and medical product innovators to achieve its lofty goals. Coupled with directives to the FDA within the 21st Century Cures Act on aspects of the regulatory science, advancements in precision medicine will introduce fundamental disruptions to the historical structure, support, and contributions in drug research and development. Signals from the drug industry indicate that there is rapid investment in precision medicine, nearly doubling over the past five years.

Moving innovative research in precision medicine into the medical marketplace will not be easy. Precision medicine poses challenges to traditional FDA regulatory paradigms. Eventual downstream medical products will involve both the initial detection of the presence (or absence) of a specific genetic variant and the subsequent drug treatment tailored to that genetic variant. This diagnosis - treatment spectrum necessarily implicates the regulatory authority of the FDA with regard to both medical devices and new human drugs and biologics. The success of the PMI will inevitably increase pressures on a regulatory system already suffering from a crisis of heavy industry and expert criticism due to its lack of clarity and transparency. Precision medicine also implicates the ongoing debate about FDA oversight of laboratory-developed tests. In a 2013 report assessing scientific promise and related regulatory obstacles, the FDA acknowledged that precision medicine ushers in a “new era of medical product development” for the agency; however, then Commissioner Hamburg emphasized that regulatory adaptation was a priority. With enactment of the 21st Century Cures Act and other recent legislation, that adaptation may actually be achievable if the FDA is willing to create flexible, dynamic regulatory approaches for innovative new products.

This article surveys the current structure of the FDA regulatory regime as it impacts precision medicine and specifically explores a category of FDA-regulated products called companion diagnostics. Part I discusses the field of precision medicine and its relationship to companion diagnostics, highlighting the historical background, incremental funding initiatives, and market trajectory for companion diagnostic products. Part II discusses the FDA institutional frameworks for regulation of traditional drug, biologic, and medical device products, as well as the FDA’s approach to companion diagnostics. Part III identifies key legislative and agency activity supporting innovation in biomedicine, including the Affordable Care Act of 2010, the FDA Safety and Innovation Act of 2012, the 21st Century Cures Act of 2016, and FDA policy on laboratory-developed tests. This Part also highlights how these may impact the development of companion diagnostics and possibly help facilitate regulatory flexibility. Part IV concludes.

Keywords: Precision medicine, companion diagnostics, drugs, medical devices, FDA, regulation, 21st Century Cures Act, innovation