Activities of FDA’s Division of Nutrition Regarding Cholesterol Oxides

A recent Food and Drug Administration (FDA) proposal aims to speed the evaluation process for new high-risk medical devices that are intended to address unmet medical needs,1 much like existing expedited approval processes, such as the humanitarian device exemption rule for devices intended to treat rare diseases. Such programs are strongly supported by the medical device industry and some patient advocacy groups, which have criticized the FDA for being too stringent in its evidentiary requirements for investigational devices, leading to delays in the approval of potentially helpful products.2–4 For example, in 2011, the FDA approved a transcatheter aortic valve replacement system that demonstrated significant improvements over conventional treatment options for selected patients with severe aortic stenosis.5,6 However, the United States was the 43rd country to approve the device, roughly 4 years after the European Union.7 Yet expedited approval for high-risk medical devices raises the possibility that these devices will not be as effective as predicted in their limited premarket testing or that they could cause unanticipated harms after approval.8 Of course, well-studied devices may present unexpected safety concerns years after approval,9,10 and even the most rigorous conventional premarket approval process will result in some devices later found to be unsafe or ineffective.11–13 Safety of approved medical devices and the proper scope of premarket testing remain contentious issues after recalls of several widely used devices, including popular models of implantable cardioverter defibrillator leads14,15 and metal-on-metal hip implants.16 Inherent limitations in premarket testing, along with the prospect of lowered evidentiary standards for expedited device reviews, place greater pressures on postapproval monitoring of devices to follow clinical performance and to identify emerging public health problems. Medical device manufacturers routinely perform this sort of vigilance, …

The US Food and Drug Administration (FDA) is a remarkable hybrid. Part regulatory agency, part public health agency, it sits at the intersection of science, law, and public policy. The FDA’s mission can be considered in the context of 2 broad dimensions: the products it regulates and its core functions. Both fall under the rubric of protecting and promoting the public health. The FDA’s remit is both broad and diverse: altogether, the agency has regulatory responsibility for >20% of the US economy. The products it is charged with overseeing through its various centers1 encompass food and cosmetics (regulated by the Center for Food Safety and Applied Nutrition); food and drugs for animals, including companion animals and animals used for food (regulated by the Center for Veterinary Medicine); and medical devices, drugs, and biologics (regulated by the Centers for Devices and Radiological Health, Drug Evaluation and Research, and Biologics Evaluation and Research, respectively). Tobacco products were added to the FDA’s portfolio by the Tobacco Control Act of 2009, and are overseen by the Center for Tobacco Products. Regardless of the specific product regulated, the FDA’s core mission remains the same: to protect the US population by helping to ensure the fundamental safety of the food Americans consume and the medical products prescribed by their clinicians. At the same time, this primary mission is complemented by a mandate to promote the public health by reviewing research and taking appropriate action on the marketing of regulated products in a timely manner. Not only do people need access to advances in nutrition and medical therapies, but also the American spirit is itself characterized by a strong current of scientific and technological innovation. At first glance, differences in these 2 priorities, protecting the public safety and promoting the public health through encouraging innovation, might …

Reporting standards for adverse events after medical device use in the peripheral vascular system

British chef and food activist Jamie Oliver ignited a firestorm in January 2011 when he mentioned on the Late Show with David Letterman that castoreum, a substance used to augment some strawberry and vanilla flavorings, comes from what he described as “rendered beaver anal gland.”1 The next year, vegans were outraged to learn that Starbucks used cochineal extract, a color additive derived from insect shells, to dye their strawberry Frappuccino® drinks2 (eventually, the company decided to transition to lycopene, a pigment found in tomatoes3). Although substances like castoreum and cochineal extract may be long on the “yuck factor,”4 research has shown them to be perfectly safe for most people; strident opposition arose not from safety issues but from the ingredients’ origins. But these examples demonstrate that the public often lacks significant knowledge about the ingredients in foods and where they come from. This is not a new development; the public relationship to food additives has a long history of trust lost, regained, and in some cases lost again. The Federal Food, Drug, and Cosmetic (FD&C) Act of 19385 was passed shortly after the deaths of 100 people who took an untested new form of a popular drug, which contained what turned out to be a deadly additive.6 The new law was consumer oriented and intended to ensure that people knew what was in the products they bought, and that those products were safe. The law has been amended over the years in attempts to streamline and bring order to the sprawling task of assessing and categorizing the thousands of substances used in foods, drugs, and cosmetics. One result of this streamlining is that under current U.S. law, companies can add certain types of ingredients to foods without premarket approval from the thin-stretched Food and Drug Administration (FDA). In other words, there are substances in the food supply that are unknown to the FDA. In 2010 the Government Accountability Office (GAO) concluded that a “growing number of substances … may effectively be excluded from federal oversight.”7 Is this a problem? The answer depends on whom you ask.

A surgeon’s perspective regarding the regulatory, compliance, and legal issues involved with physician-modified devices

Innovation in Health Care: Time for a Gut Check

Bringing New Technologies to Market: Hurdles and Solutions

Evaluating consumer and clinical sleep technologies: an American Academy of Sleep Medicine update

The development and introduction of new medical devices have radically changed the practice of medicine. No area of medicine has been affected more than cardiology, with new devices facilitating the effective treatment of coronary artery disease (percutaneous coronary interventions [PCIs]/stents), valvular heart disease (mechanical and bioprosthetic valves), and electrophysiological disorders (pacemakers and automatic implantable cardiodefibrillators). In addition to fueling the growth of the medical device industry, this explosion of technology has driven the development of new medical subspecialties, eg, interventional cardiology and electrophysiology. Other areas of medicine, including orthopedics and general surgery, have witnessed similar transformations. The current regulatory pathway for a significant-risk first-in-class medical device is typically a long, expensive, and risky process, culminating in a pivotal trial designed to demonstrate safety and efficacy. The pivotal trial phase is typically the most time-consuming and costly phase of the process. In the United States, medical devices are regulated by the Center for Devices and Radiological Health at the Food and Drug Administration (FDA), which has been charged by Congress to seek the “least burdensome means” when determining the scope of data required to evaluate the safety and efficacy necessary for device approval.1 Thus, pivotal trials by intention are designed to select patient cohorts most likely to demonstrate procedural benefit while limiting patient/study subject risk within the shortest time frame that can provide meaningful data. The realities of logistics, time, and resources limit the size and duration of most new device trials to 800 to 1500 patients, limiting the power of these trials to detect events with an occurrence rate of <1%. Furthermore, pivotal trials are conducted by the most experienced physician operators at medical centers with sufficient patient volume and research infrastructure to recruit and conduct clinical studies. Some have questioned whether results obtained under these settings from such …

Theranos Experience Exposes Weaknesses in FDA Regulatory Discretion.

The U.S. Food and Drug Administration (FDA) is accountable for the safety and security of human and veterinary drugs, biological products, much of the U.S. food supply, devices that emit radiation, cosmetics, and medical devices. Title III of the Bioterrorism Preparedness and Response Act of 2002 specifically designates the FDA as being responsible for the safety and integrity of the nation's food and drug supply, and recognizes FDA's oversight of 80 per cent of the entire U.S. food supply. The FDA must provide for the security of both finished food products within United States and the facilities involved in domestic and imported food manufacture and processing. Further, on May 30, 2002, the FDA announced a new regulation aiming to expedite approval of drugs and other products developed to reduce or mitigate the effects of biological, chemical, or radiological terrorism agents. The FDA's responsibilities in food security and counterterrorism are reviewed.

“Black box” 101: How the Food and Drug Administration evaluates, communicates, and manages drug benefit/risk

Successful Investigational New Drug Preparation without Reinventing the Wheel

The U.S. Food and Drug Administration (FDA) has been concerned with minimizing the unnecessary radiation exposure of people for half a century. Manufacturers of medical X-ray imaging devices are important partners in this effort. Medical X-ray imaging devices are regulated by FDA under both its electronic product regulations andits medical device regulations. FDA also publishes guidance documents that represent FDA's current thinking on a topic and provide a suggested or recommended approach to meet the requirements of a regulation or statute. FDA encourages manufacturers to develop medical devices that conform to voluntary consensus standards. Use of these standards is a central element of FDA's system to ensure that all medical devices marketed in the U.S. meet safety and effectiveness requirements. FDA staff participate actively in the development and maintenance of these standards, often advancing or introducing new safety and dose management requirements. Use of voluntary consensus standards reduces the amount of time necessary to evaluate a premarket submission and reduces the burden on manufacturers. FDA interacts with industry and other stakeholders through meetings with industry groups, public meetings, public communications, and through the development of voluntary consensus standards. In these interactions, FDA staff introduce new concepts for improving the safety of these devices and provide support for similar initiatives from professional organizations. FDA works with all stakeholders to achieve its mission of protecting and promoting the public health.

FDA reform plan edges closer to realisation