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Policy Points This article describes a strategic combination of research, advocacy, corporate campaigns, communications, grassroots mobilization, legislation, regulatory actions, and litigation against companies and government to secure a national policy to remove artificial trans fat from the US food system. Sharing lessons we learned can help inform policymakers, academics, policy practitioners, and students across disciplines. Some of our lessons are that system change means that all consumers benefit without the need for individual behavior change; research can both identify opportunities to improve health and support policy adoption; policy efforts can serve as public education campaigns; policy campaigns can drive marketplace changes; and engaging forward-thinking companies can diffuse opposition to passing a policy., Context: For many decades, partially hydrogenated vegetable oil (PHO), the primary source of artificial trans fat in the American diet, was used widely in processed and restaurant foods. In the early 1990s, studies linked the consumption of artificial trans fat with heart disease. This article details how research and advocacy led to eliminating artificial trans fat from the US food supply., Methods: We synthesized published studies of the health impact of trans fat, the legislative history of state and local trans fat bills, the Food and Drug Administration's (FDA) regulatory docket on trans fat labeling and its declaration that PHOs are no longer Generally Recognized as Safe (GRAS), and our own files, which included strategy documents, notes from meetings with the FDA staff, correspondence between advocates and the FDA, fact sheets, press releases, news clips, and other materials., Findings: This history of trans fat provides insights into policy strategy and advocacy best practices that resulted in the removal of trans fat from food in the United States, preventing an estimated 50,000 premature deaths a year. The lessons we learned are that system change benefits all consumers without the need for individual behavior change; research can both identify opportunities to improve health through policy and support policy adoption; policy campaigns can serve as public education campaigns; policy can drive changes to products and the marketplace; and engaging forward-thinking companies can help diffuse opposition to passing a policy. Securing this policy required the persistence of scientists and health advocates in first discovering the risks and then using the science to secure policies to mitigate the identified harm., Conclusions: An understanding of the tactics used to help attain the targeted policies and how challenges were addressed (such as through communications, leveraging an expanding research base and expert reports, showing that a national policy was feasible through voluntary corporate changes and state and local policy, and litigation against companies and government agencies) may provide a model for scientists, students, advocates, and policymakers. We hope this account will inform efforts to address other public health challenges, such as the current threats of excessive exposure to sodium and added sugars, which persist in the US food system., (© 2021 Milbank Memorial Fund.)

Importance: US law generally requires testing of high-risk medical devices prior to approval, as well as premarket evaluation of moderate-risk medical devices, with the goal of ensuring that the benefits of these products exceed their risks. The US Food and Drug Administration (FDA) attempts to balance the need for evidence generation with an approval process that facilitates access and encourages innovation., Objective: To review the development of laws and standards affecting the evaluation and oversight of medical devices by the US regulatory system and the outcomes of this system from 1976 to 2020., Evidence Review: Laws enacted by US Congress and regulations promulgated by the FDA through 2020; databases maintained by the FDA of device authorizations from 1976 to 2020; and annual reports of user fees paid to the FDA by industry., Findings: Since Congress and the FDA initiated premarket review of medical devices in 1976, some fundamental innovations in the device regulation system have included special pathways to accelerate availability of investigational devices, more flexible evidence and review requirements, and increased funding to the FDA through industry-paid user fees. From 1987 to 2020, the annual number of novel devices granted premarket approval (which excludes supplements) ranged from 8 to 56 (median, 32), and the number of clearances for 510(k) devices (those that are "substantially equivalent" to marketed devices) ranged from 2804 to 5762 (median, 3404). User fee funding for devices was established in 2002 and annual fees collected increased from $30 million in 2003 (in 2019 dollars) to more than $208 million in 2019; this represented 43% of FDA funding related to the review of medical devices. Although many new devices have led to considerable patient benefit, such as hypodermic needles and magnetic resonance imaging machines, important adverse events caused by some devices, such as an implanted device for birth control and a surgical mesh implant for pelvic organ prolapse, have led to calls to reexamine the regulatory system for such products., Conclusions and Relevance: Over the last 45 years, medical device regulation has become more complex, with more regulatory pathways and greater variations in the evidence and controls required for authorization. Increased FDA support from industry and concern about flexible authorization requirements reflect the tension between efficient access and the need for assurances that products will safely benefit patients.

Women's health activists laid the groundwork for passage of the law that created the U.S. Food and Drug Administration in 1906. The pharmaceutical and food industries fought regulatory reforms then and continue to do so now. We examine public health activism in the Progressive Era, the postwar era and the present day. The women's health movement began in the 1960s, and criticized both the pharmaceutical industry and the medical establishment. In the 1990s, patient advocacy groups began accepting industry funds; thousands of commercially-funded groups now dominate the advocacy landscape. As pharma funding became normalized, concerns arose regarding a) the lack of transparency and public accountability regarding funding, b) the distortion of groups' agendas, and c) the ability of pharma-funded groups to dominate the discourse and override less well-resourced patient and health advocacy groups. Although industry-funded groups argue that funding allows them to provide useful services, the trade-off in health risks, exorbitant prices and distorted information is far too high. Sincerity is beside the point; patients and the industry have differing interests when it comes to drug safety and efficacy, drug information and drug prices. A growing resistance movement is asserting the values of its activist predecessors and opposing the prevailing culture of pharma-funded advocacy.

During 2019, the US Food and Drug Administration (FDA) approved 48 new drugs (38 New Chemical Entities and 10 Biologics). Although this figure is slightly lower than that registered in 2018 (59 divided between 42 New Chemical Entities and 17 Biologics), a year that broke a record with respect to new drugs approved by this agency, it builds on the trend initiated in 2017, when 46 drugs were approved. Of note, three antibody drug conjugates, three peptides, and two oligonucleotides were approved in 2019. This report analyzes the 48 new drugs of the class of 2019 from a strictly chemical perspective. The classification, which was carried out on the basis of chemical structure, includes the following: Biologics (antibody drug conjugates, antibodies, and proteins); TIDES (peptide and oligonucleotides); drug combinations; natural products; and small molecules.

Since the dawn of breast implantation back in the sixties, five generations of breast implants have tried to provide the most natural-looking results while striving to eliminate the risk of unpleasant ruptures or capsular contractures. National Health regulators (i.e. the FDA in USA and ANSM in France) have had an "after the facts" reaction, which led to a so-called "dirty war" among producers in the form of a 1992 Silicone's Moratorium (after suspicions of associated cancer or immune-related disorders) all this under the rigid oversight of a FDA director, who seemed more sensible to media scandal than scientific data. After more than a decade of consistent scientific evidence, the interdiction was finally ended in France in 2001 and in the USA in 2006, however the scandals resurfaced again in 2011 after a proven fraud on the "PIP - affair" and most recently with "breast implant associated - anaplastic large cell lymphoma", an extremely serious and rare pathology, treated only by surgical means, until further research. We describe also a chronology on the way the FDA finally recognized this dramatic complication., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1950s by Burroughs Wellcome and Company (BW Co) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects was disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects., Sources: Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, IL. We consulted documents submitted by BW Co to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks., Results: Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co's packaging contained warnings as early as the 1950s but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia., Conclusion: Particularly given the regulatory environment of the time, BW Co appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine., (Copyright © 2018 Anesthesia History Association. Published by Elsevier Inc. All rights reserved.)

Data integrity is critical to regulatory compliance, and the fundamental reason for 21 CFR Part 11 published by the U.S. Food and Drug Administration (FDA). FDA published the first guideline in 1963, and since then FDA and European Union (EU) have published numerous guidelines on various topics related to data integrity for the pharmaceutical industry. Regulators wanted to make certain that industry capture accurate data during the drug development lifecycle and through commercialization-consider the number of warning letters issued lately by inspectors across the globe on data integrity. This article discusses the history of regulations put forward by various regulatory bodies, the term ALCOA Plus adopted by regulators, the impact of not following regulations, and some prevention methods by using some simple checklists, self-audit, and self-inspection techniques. FDA uses the acronym ALCOA to define its expectations of electronic data. ALCOA stands for Attributable, Legible, Contemporaneous, Original, and Accurate. ALCOA was further expanded to ALCOA Plus, and the Plus means Enduring, Available and Accessible, Complete, Consistent, Credible, and Corroborated. If we do not follow the regulations as written, then there is a huge risk. This article covers some of the risk aspects. To prevent data integrity, various solutions can be implemented such as a simple checklist for various systems, self-audit, and self-inspections. To do that we have to develop strategy, people, implement better business processes, and gain a better understanding of data lifecycle as well as technology. LAY ABSTRACT: If one does a Google search on "What is data integrity?" the first page will give the definition of data integrity, how to learn more about data integrity, the history of data integrity, risk management of data integrity, and at the top about various U.S. Food and Drug Administration (FDA) and European Union (EU) regulations. Data integrity is nothing but about accuracy of data. When someone searches Google for some words, we expect accurate results that we can rely on. The same principle applies during the drug development lifecycle. Pharmaceutical industry ensures that data entered for various steps of drug development is accurate so that we can have confidence that the drugs produced by the industry are within some parameters. The regulations put forward by FDA and EU are not new. The first regulation was published in 1963, and after that regulators published multiple guidelines. Inspectors from both regulatory bodies inspected the industry, and they found that the data was not accurate. If pharmaceutical industry produces drugs within the stated parameters, then it is approved and available in the market for patients. If inspectors find that the data is modified, then the drug is not approved. That means revenue loss for industry and drugs not available for patients. In this article, I explain some of the remediation plans for the industry that can be applied during the drug development lifecycle pathway., (© PDA, Inc. 2018.)

This article traces the history of the US FDA regulation of nutrition labeling, identifying an 'informational turn' in the evolving politics of food, diet and health in America. Before nutrition labeling was introduced, regulators actively sought to segregate food markets from drug markets by largely prohibiting health information on food labels, believing such information would 'confuse' the ordinary food consumer. Nutrition labeling's emergence, first in the 1970s as consumer empowerment and then later in the 1990s as a solution to information overload, reflected the belief that it was better to manage markets indirectly through consumer information than directly through command-and-control regulatory architecture. By studying product labels as 'information infrastructure', rather than a 'knowledge fix', the article shows how labels are situated at the center of a legally constructed terrain of inter-textual references, both educational and promotional, that reflects a mix of market pragmatism and evolving legal thought about mass versus niche markets. A change to the label reaches out across a wide informational environment representing food and has direct material consequences for how food is produced, distributed, and consumed. One legacy of this informational turn has been an increasing focus by policymakers, industry, and arguably consumers on the politics of information in place of the politics of the food itself.

This article rethinks the formative decades of American drug wars through a social history of addiction to pharmaceutical narcotics, sedatives, and stimulants in the first half of the twentieth century. It argues, first, that addiction to pharmaceutical drugs is no recent aberration; it has historically been more extensive than "street" or illicit drug use. Second, it argues that access to psychoactive pharmaceuticals was a problematic social entitlement constructed as distinctively medical amid the racialized reforms of the Progressive Era. The resulting drug control regime provided inadequate consumer protection for some (through the FDA), and overly punitive policing for others (through the FBN). Instead of seeing these as two separate stories-one a liberal triumph and the other a repressive scourge-both should be understood as part of the broader establishment of a consumer market for drugs segregated by class and race like other consumer markets developed in the era of Progressivism and Jim Crow.

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development., (© The Author(s) 2016.)

In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In 2015, U.S. government agencies began considering greater regulation of both homeopathic drugs and the advertising of such products. These actions came after more than a century of missed opportunities to regulate homeopathic medicines.

Cancer is a close second to heart disease for cause of death in the USA, and could soon surpass heart disease as the population ages and the incidence of cancer continues to increase. While heart disease can be addressed through behavior modification and education (e.g., smoking cessation, dietary changes, exercises that promote cardiovascular fitness), pharmacology and improved surgical devices and methods, cancer ultimately requires improved and novel drug treatments to bring mortality rates down. In 2014, the US FDA approved 17 drugs and/or drug combinations in 12 disease sites for a total of 19 indications in melanoma, hematologic malignancies, gastrointestinal carcinoma, non-small-cell lung cancer, gynecologic malignancies and lymphoma/lymphoproliferative disorders.

This article summarizes the history of the regulation of caffeine, a key component of caffeine-containing energy drinks and other caffeine-containing energy products, in the United States. Caffeine as an ingredient in food has been regulated by the US Food and Drug Administration (FDA) since 1958, when the Food Additives Amendment to the Federal Food, Drug and Cosmetic Act was enacted. It is listed as a substance that is generally recognized as safe by experts for its intended use in cola-type beverages at levels not to exceed 200 parts per million. Here, the history of FDA evaluations of the safe use of, as well as consumer exposure to, caffeine in food in the United States is outlined. Finally, the FDA's current concerns about caffeine and caffeine-containing energy products are reported, along with the current activities to address those concerns., (Published 2014. This article is a U.S. government work and is in the public domain in the USA.)

An outbreak of cataracts in 1935 caused by dinitrophenol (DNP), the active ingredient of popular diet pills, highlighted the inability of the U.S. Food and Drug Administration (FDA) to prevent harmful drugs from entering the marketplace. Just two years earlier, the FDA used horrific images of ocular surface injury caused by cosmetics at the World's Fair in Chicago to garner public support for legislative reform. The FDA had to walk a fine line between a public awareness campaign and lobbying Congress while lawmakers debated the need for consumer protection. The cataract outbreak of 1935 was conspicuous in the medical literature during the height of New Deal legislation, but questions persist as to how much it affected passage of the proposed Food, Drug, and Cosmetic Act (of 1938). The legislation languished in committee for years. The cataract outbreak probably had little impact on the eventual outcome, but medical opinion concerning the safety of DNP may have contributed to the voluntary withdrawal of the diet drug from the market. We review the DNP cataract outbreak and examine it in context of the challenges facing regulatory reform at that time., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The decision to approve a drug for clinical use is based on an understanding of its benefits versus the risks. Although efficacy is generally understood at the time of submission to the FDA for approval, the risks are more difficult to assess. Both PubMed (from 2000 to 2012) and the FDA website (www.fda.gov) were searched using the search terms "risk evaluation and mitigation strategy" (REMS). Articles for review were selected by relevance to topic, and their references were searched as well for additional relevant resources. Since the search results were not expected to contain research studies, formal quality assessment and inclusion and exclusion criteria were not utilized resulting in a narrative review. Few directly relevant research studies exist, although supporting documents such as government reports were available. For effective drugs with unclear or concerning safety records, the FDA has the option of requiring a risk evaluation and mitigation strategy, which allows a systematic approach to track and assure safe medication use. Over 100 different medications are currently covered by REMS, and each REMS is developed individually based on the needs of the specific drug or class. Although likely associated with improvements in medication safety, the potential benefit, limitations, and consequences of REMS are not yet fully understood.

Medical devices are of increasing importance in cardiovascular disease and have made important contributions to patient care. These devices continue to evolve with increasing complexity. FDA regulation of medical devices involves increased stringency for higher risk and novel devices. However, there are some current opportunities to strengthen the FDA's pre-approval regulatory process and improve post-marketing surveillance. This article reviews FDA regulation of cardiovascular devices and offers suggestions for strengthening the process while focusing on examples relevant to cardiac electrophysiologists.

The rapidly evolving realm of modern commerce strains traditional regulatory paradigms. This paper traces the historical evolution of FDA crisis-response regulation and provides examples of ways in which the definitions and procedures resulting from that past continue to be challenged by new products as market entrants, some in good faith and others not, take actions that create disconnects between actual product and marketing controls and those that consumers might expect. The paper then explores some of the techniques used by other federal agencies that have faced similar challenges in environments characterized by rapid innovation, and draws from this analysis suggestions for improvement of the FDA's warning letter system.

The development of antimicrobial drugs has evolved from observational case reports to complex randomized prospective clinical trials in specific treatment indications. Beginning around the year 2000, the US FDA has evolved its approach on study design and other study characteristics, which has made the conduct of these studies more difficult and the outcomes for sponsors more risky. This has contributed to the decline in the discovery and development of new antimicrobials, which are needed to address the increasing problem of bacterial resistance to existing marketed products. This study reviews the historical basis for the current regulatory climate including the various crises that have led to considerable political pressures on the agency. Recent efforts to resolve development uncertainties and to provide economic incentives for future antimicrobial drug development are presented.

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies., (Copyright © 2012. Published by Elsevier B.V.)

The US Food and Drug Administration is expected to approve AquAdvantage Salmon as the first genetically modified animal for human consumption. The genetic modifications allow the proprietary fish to grow at a rate twice as fast as a wild salmon, leading to greater ‘efficiency’ in terms of reduced costs and reduced time to market. This article provides an analysis of the ways in which AquAdvantage Salmon exemplifies capitalist market forces controlling and guiding the terms of salmon recovery and conservation. The authors trace historical developments within the salmon industry to demonstrate how capitalist commodity production has impacted fishing communities. They reject the oft-cited ‘tragedy of the commons’ hypothesis offered to explain fisheries crises. In its place, they offer the conceptual framework of the ‘tragedy of the commodity’ to explore how capitalist market forces and complicit state regulations amplify rather than resolve global environmental problems.