Information Opacity in Biopharmaceutical Innovation Through the Lens of COVID-19.

The COVID-19 pandemic has revealed myriad and complex challenges for our national health care system spanning preparedness, response, access, costs, infrastructure, coordination, and medical innovation. These challenges implicate federal, state, and local agencies and actors, as well as international collaborative bodies. One constant throughout the pandemic has been the pressing need for safe and effective diagnostics, prophylactic vaccines, and drug treatments to counter the virus.1 Inarguably, significant problems with the multi-faceted system of drug and vaccine innovation and regulation manifested long before the COVID-19 pandemic.2 The pandemic, however, has laid bare the inextricable connections among federal funding, patents, product review and approval mechanisms, and the eventual medical products and resulting costs.

The CRISPR Patent Ruling and Implications for Medicine.

This Viewpoint discusses the CRISPR patent ruling, an ongoing patent dispute, and the implications for research and medical innovation.

21st Century Citizen Pharma: The FDA & Patient-Focused Product Development.

Perpetual debate regarding the delicate balance between access and innovation and the protection of the public health and safety dominate discussions of the United States Food and Drug Administration ("FDA"). Established chiefly as a command and control federal administrative agency, iterative changes in legislation have shaped the FDA's activity in drug, biologic, and medical device regulation over the course of the last one hundred plus years. The most recent fundamental reframing of the agency's authority and directive presented itself in the 21st Century Cures Act, reflecting an important role for patient perspectives in the regulatory process. This Article explores recent developments in patient-focused product development efforts at the FDA and offers modest insights on the increasing role of patients, and patient advocacy groups, in agency decision-making. The Article terms this era "21st century citizen pharma."

The Legal and Regulatory Status of Biosimilars: How Product Naming and State Substitution Laws May Impact the United States Healthcare System.

Alongside the constitutional controversy ultimately addressed by the Supreme Court, the colossal Patient Protection and Affordable Care Act (ACA) ushered in a new paradigm for regulation of biologics by the Food and Drug Administration (FDA). Nestled within the expansive ACA, the Biologics Price Competition and Innovation Act (BPCIA) set forth an abbreviated pathway to market for "biosimilar" and "interchangeable" biological products. While the current BPCIA implementation debate focuses chiefly on the scope of scientific and technical assessments by the FDA and the effect on the emergent biosimilar industry, two issues will prove essential for determinations of access to and costs of the resulting products: how the biosimilar and interchangeable biosimilar biologics are to be named, and whether pharmacist substitution is appropriate for products the FDA deems interchangeable. This article examines the current debate surrounding the use of nonproprietary names for biosimilar biologics, as well as state efforts to reconcile automatic substitution laws for the eventual products. In particular, the article addresses the implications for patients and the United States health care system, highlighting the potential negative effect on anticipated cost-savings, hindrances for effective tracking and reporting of adverse events, and a general lack of consistency in state laws.

Electronic cigarettes: smoke-free laws, sale restrictions, and the public health.

Consumer use of e-cigarettes is rising despite a lack of rigorous safety testing, manufacturing controls, and a well-understood risk profile. Many states and municipalities have prohibited e-cigarette sale to minors or amended their smoke-free laws to restrict public use. I discuss the public health impact of e-cigarettes and the current lack of Food and Drug Administration regulation, and advocate that states and localities reexamine their smoke-free laws and sale restrictions to appropriately regulate public use and youth access.

No sisyphean task: how the FDA can regulate electronic cigarettes.

The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009 (TCA). It examines the tumultuous history of attempts at tobacco regulation by reflecting on the history of Congressional activity to regulate tobacco sales and promotion. Furthermore, this Article suggests a feasible approach to strengthening regulation of e-cigarettes under the existing statutory framework. This approach includes increased scrutiny of manufacturer and distributor claims that trigger drug and medical device provisions, utilization of new tobacco product and modified risk tobacco product provisions, and promulgation of new FDA regulations and guidance specifically directed at e-cigarettes.

Mifepristone Paternalism at the FDA.

This article explores the role of the Food and Drug Administration (FDA) in drug approval and restrictions to mifepristone access in the context of historical regulation and current litigation.

Foreword: Follow-on Biologics: Implementation Challenges and Opportunities.

This Book of the Seton Hall Law Review presents the contributions to Follow-On Biologics: Implementation Challenges and Opportunities, a one-day roundtable event hosted by Seton Hall University School of Law in the fall of 2010. The roundtable fostered an international dialogue regarding the future of follow-on biologics in the United States resulting from the Patient Protection and Affordable Care Act of March 2010. THE BIOLOGIC PRICE COMPETITION AND INNOVATION ACT OF 2010. The March 23, 2010, enactment of the Patient Protection and Affordable Care Act (PPACA) and the companion Health Care and Education Affordability Reconciliation Act of 2010 ushered in landmark reform of the American health care system. Along with sweeping overhauls of the health care system generally, PPACA also provides a new regulatory challenge for the Food and Drug Administration (FDA). A subtitle within PPACA, the Biologics Price Competition and Innovation Act (BPCIA), bestows upon FDA broad authority to implement an abbreviated approval route to market for biological products (also known as biologics) that are "biosimilar" to an existing marketed product. The brief introduction will provide a basic comparison of biologics and conventional pharmaceutical drugs that will prove central to the FDA's development of this follow-on biologic pathway as well as specifically examine the content and scope of the BPCIA provisions and identify future challenges for the FDA. It will conclude by highlighting details of presentations during the roundtable held at the Seton Hall University School of Law and introduce the two resulting articles contained with this Book of the Seton Hall Law Review.

COVID-IP: staring down the Bayh-Dole Act with 2020 vision.

As the human and economic toll of the COVID-19 coronavirus steadily escalates, there is extreme uncertainty regarding the timeframe for prevention, detection, and treatment. There is also concern about the eventual costs associated with approved products and the barriers to access created by the patent system. Industry, government, and academic collaborations are leading the charge in the discovery race, partnerships which have triggered calls for the activation of the federal governments so-called ``march-in rights'' established in the Bayh-Dole Act. The Bayh-Dole Act dramatically altered the patent protections available to federally funded institutions and initiated a 40-year debate over appropriate incentives for innovation and the scope of the government's authority. The COVID-19 pandemic provides an opportunity to reflect on the purpose and impact of the historic legislation as well as contemplate the implications for our public health future. Patent rights for therapeutic compounds, methods of delivery, and medical diagnostics will significantly impact access to and cost of life-saving innovations. This article examines current calls for the U.S. government to utilize governmental march-in rights to quell concerns about patent monopolization and product pricing in the face of our current pandemic.

Regulating Nanomedicine at the Food and Drug Administration.

The US Food and Drug Administration (FDA) oversees safety and efficacy of a broad spectrum of medical products (ie, drugs, biologics, and devices) under the auspices of federal legislation and agency regulations and policy. Complex and emerging nanoscale products challenge this regulatory framework and illuminate its shortcomings for combination products that integrate multiple mechanisms of therapeutic action. This article surveys current FDA regulatory structures and nanotechnology-specific guidance, discusses relevant nanomedicine products, and identifies regulatory challenges.

An integrated approach to oversight assessment for emerging technologies.

Analysis of oversight systems is often conducted from a single disciplinary perspective and by using a limited set of criteria for evaluation. In this article, we develop an approach that blends risk analysis, social science, public administration, legal, public policy, and ethical perspectives to develop a broad set of criteria for assessing oversight systems. Multiple methods, including historical analysis, expert elicitation, and behavioral consensus, were employed to develop multidisciplinary criteria for evaluating oversight of emerging technologies. Sixty-six initial criteria were identified from extensive literature reviews and input from our Working Group. Criteria were placed in four categories reflecting the development, attributes, evolution, and outcomes of oversight systems. Expert elicitation, consensus methods, and multidisciplinary review of the literature were used to refine a condensed, operative set of criteria. Twenty-eight criteria resulted spanning four categories: seven development criteria, 15 attribute criteria, five outcome criteria, and one evolution criterion. These criteria illuminate how oversight systems develop, operate, change, and affect society. We term our approach "integrated oversight assessment" and propose its use as a tool for analyzing relationships among features, outcomes, and tradeoffs of oversight systems. Comparisons among historical case studies of oversight using a consistent set of criteria should result in defensible and evidence-supported lessons to guide the development of oversight systems for emerging technologies, such as nanotechnology.

The law of incidental findings in human subjects research: establishing researchers' duties.

Research technologies can now produce so much information that there is significant potential for incidental findings (IFs). These are findings generated in research that are beyond the aims of the study. Current law and federal regulations offer no direct guidance on how to deal with IFs in research, nor is there adequate professional or institutional guidance. We advocate a defined set of researcher duties based on law and ethics and recommend a pathway to be followed in handling IFs in research. This article traces the underlying ethical and legal theories supporting researcher duties to manage IFs, including duties to develop a plan for management in the research protocol, to discuss the possibility of and management plan for IFs in the informed consent process, and to address, evaluate, and ultimately offer to disclose IFs of potential clinical or reproductive significance to research participants when they arise.

Managing incidental findings in human subjects research: analysis and recommendations.

No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.

Evaluating oversight of human drugs and medical devices: a case study of the FDA and implications for nanobiotechnology.

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight.

Developing U.S. oversight strategies for nanobiotechnology: learning from past oversight experiences.

The emergence of nanotechnology, and specifically nanobiotechnology, raises major oversight challenges. In the United States, government, industry, and researchers are debating what oversight approaches are most appropriate. Among the federal agencies already embroiled in discussion of oversight approaches are the Food and Drug Administration (FDA), Environmental Protection Agency (EPA), Department of Agriculture (USDA), Occupational Safety and Health Administration (OSHA), and National Institutes of Health (NIH). All can learn from assessment of the successes and failures of past oversight efforts aimed at emerging technologies. This article reports on work funded by the National Science Foundation (NSF) aimed at learning the lessons of past oversight efforts. The article offers insights that emerge from comparing five oversight case studies that examine oversight of genetically engineered organisms (GEOs) in the food supply, pharmaceuticals, medical devices, chemicals in the workplace, and gene therapy. Using quantitative and qualitative analysis, the authors present a new way of evaluating oversight.

Decoding the research exemption.

While debate continues as to whether genetic sequences, which many argue represent natural phenomena rather than inventions, should be subject to standard patent protections, issuance of patents that claim DNA sequences remains common practice. In an attempt to insulate researchers from patent claims that could hinder scientific progress, many countries have provided general exemptions for scientific research. However, there is no international consensus about the extent of required protections, and even existing exemptions vary widely in clarity and are limited in practical application. We believe that gene patents raise several unique issues that are inadequately handled by the current research exemptions.