Food And Drug Administration Staff Research Articles

Informed options trading before FDA drug advisory meetings

Months before the Food and Drug Administration (FDA) decides to approve or reject a new drug, it often asks committees of drug experts for their recommendations. The experts receive nonpublic technical reports from drug firms and FDA staff. We find significant abnormal options trading before the final reports are created and the committees meet, particularly for small drug firms. These options trades appear to be informed because there are more calls (puts) purchased before approvals (rejections), and a majority have maturities covering the dates when the reports are publicly released. Our results imply that securities regulators should consider monitoring trades early, well before FDA drug approval decisions.

Artificial Intelligence-Enabled Software Prototype to Inform Opioid Pharmacovigilance From Electronic Health Records: Development and Usability Study.

The use of patient health and treatment information captured in structured and unstructured formats in computerized electronic health record (EHR) repositories could potentially augment the detection of safety signals for drug products regulated by the US Food and Drug Administration (FDA). Natural language processing and other artificial intelligence (AI) techniques provide novel methodologies that could be leveraged to extract clinically useful information from EHR resources. Our aim is to develop a novel AI-enabled software prototype to identify adverse drug event (ADE) safety signals from free-text discharge summaries in EHRs to enhance opioid drug safety and research activities at the FDA. We developed a prototype for web-based software that leverages keyword and trigger-phrase searching with rule-based algorithms and deep learning to extract candidate ADEs for specific opioid drugs from discharge summaries in the Medical Information Mart for Intensive Care III (MIMIC III) database. The prototype uses MedSpacy components to identify relevant sections of discharge summaries and a pretrained natural language processing (NLP) model, Spark NLP for Healthcare, for named entity recognition. Fifteen FDA staff members provided feedback on the prototype's features and functionalities. Using the prototype, we were able to identify known, labeled, opioid-related adverse drug reactions from text in EHRs. The AI-enabled model achieved accuracy, recall, precision, and F1-scores of 0.66, 0.69, 0.64, and 0.67, respectively. FDA participants assessed the prototype as highly desirable in user satisfaction, visualizations, and in the potential to support drug safety signal detection for opioid drugs from EHR data while saving time and manual effort. Actionable design recommendations included (1) enlarging the tabs and visualizations; (2) enabling more flexibility and customizations to fit end users' individual needs; (3) providing additional instructional resources; (4) adding multiple graph export functionality; and (5) adding project summaries. The novel prototype uses innovative AI-based techniques to automate searching for, extracting, and analyzing clinically useful information captured in unstructured text in EHRs. It increases efficiency in harnessing real-world data for opioid drug safety and increases the usability of the data to support regulatory review while decreasing the manual research burden.

Med Check: FDA Actions on Xylazine, Austedo XR, and Zuranolone

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: FDA Actions on Xylazine, Austedo XR, and ZuranoloneTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:23 Mar 2023https://doi.org/10.1176/appi.pn.2023.05.4.1FDA Aims to Curtail Illegal Importation of XylazineThe U.S. Food and Drug Administration (FDA) has taken action to restrict the illegal entry of xylazine ingredients and drug products into the country, according to an announcement released in February. Xylazine is a veterinary medication used to sedate large animals such as horses and deer. However, it has increasingly been found in illicit drugs such as illicitly manufactured fentanyl, and xylazine-related overdose deaths have risen in recent years (Psychiatric News, “Xylazine Increasingly Found in Overdose Deaths”).The FDA’s actions include heightened scrutiny of imports of drugs containing xylazine into the country, and FDA staff may detain shipments if they appear to violate the law. When FDA staff conduct entry reviews of xylazine, they will consider specific evidence offered by importers that the incoming product is properly labeled, not adulterated, and for legitimate veterinary use.According to the announcement, the FDA and its Office of Criminal Investigations are collaborating with federal, state, and local partners to investigate xylazine-related activities that could be subject to criminal prosecution, including online and in-person conduct. The FDA said it is coordinating with stakeholders in animal health to ensure that drugs containing xylazine are available to veterinarians for legitimate use.SAMHSA Publishes Advisory About Cannabidiol ProductsIn February the Substance Abuse and Mental Health Services Administration (SAMHSA) published an advisory about the potential harms, side effects, and unknowns of cannabidiol (CBD).The advisory covers how CBD is derived and how it differs from delta-9-tetrahydrocannabinol (THC). The advisory also explains that CBD products that are not approved do not have to meet any standards for content or potency (Psychiatric News, “Most OTC Cannabinoid Products Mislabeled”). It notes that the FDA has not approved CBD products to be marketed as food additives or dietary supplements and that the FDA has concluded that a new regulatory pathway is needed for CBD products.The advisory provides tips and action steps for health professionals, parents, caregivers, and the general public to take regarding education and awareness of the risk of CBD products.Austedo XR Approved for Treating Tardive Dyskinesia and Huntington’s ChoreaThe FDA has approved Austedo XR (deutetrabenazine extended-release tablets) for the treatment of tardive dyskinesia and chorea associated with Huntington’s disease in adults, Teva Pharmaceuticals announced in February. Austedo XR is taken once per day, compared with Austedo, which is taken twice per day. It will be available in three strengths: 6 mg, 12 mg, and 24 mg, and can be taken with or without food. The same total daily dosage can be used when switching between Austedo tablets and Austedo XR tablets.Austedo XR comes with a boxed warning about depression and suicidality in patients with Huntington’s disease. The warning instructs health professionals who prescribe the medication to monitor patients who take Austedo for the emergence or worsening of depression, suicidality, or changes in behavior. It also instructs health professionals to inform patients, caregivers, and families of the risk of depression and suicidality.FDA Grants Zuranolone Priority Review for Major Depression and Postpartum DepressionThe FDA has granted zuranolone priority review for the treatment of major depressive disorder (MDD) and postpartum depression (PPD), Sage Therapeutics announced in February. Zuranolone is an investigational drug being evaluated as a 14-day, rapid-acting, once-daily, oral treatment in adults with MDD and PPD.In the WATERFALL trial, 543 adults aged 18 to 64 years with MDD received either 50 mg of zuranolone or placebo daily for 14 days. All patients in the study had a Hamilton Rating Scale for Depression (HAMD-17) total score of at least 24 when they enrolled in the study. By day 15 of the trial, patients who took zuranolone had experienced an average drop of 14.1 points on the HAMD-17, compared with an average drop of 12.3 points in those who took placebo.In the SKYLARK trial, 195 women with PPD were randomized to take either 50 mg of zuranolone or placebo once per night for 14 days. On Day 15, scores on the 17-item Hamilton Rating Scale for Depression dropped a mean of 15.6 points among women who took zuranolone compared with a mean decrease in score of 11.6 points among women who took placebo.The FDA’s decision on whether to approve zuranolone for major depressive disorder and postpartum depression is expected by August 5. ■ ISSUES NewArchived

Proceedings: PET Drugs-A Workshop on Inspections Management and Regulatory Considerations.

Recent advances in the development of new molecular imaging agents for PET have led to the approval of several new molecular entities for PET imaging by the U.S. Food and Drug Administration (FDA) within the last 10 y. However, the continued use of PET drugs for diagnostic imaging procedures is reliant on a sustainable network of PET manufacturing facilities operating in accordance with the regulations for current good manufacturing practices for PET drugs (title 21, Code of Federal Regulations, part 212). With this goal in mind, a public workshop entitled "PET Drugs: A Workshop on Inspections Management and Regulatory Considerations" was held on the FDA campus in Silver Spring, MD, on February 21, 2020. The workshop was cosponsored by the FDA's Center for Drug Evaluation and Research, the Society of Nuclear Medicine and Molecular Imaging, the Medical Imaging Technology Alliance, and the World Molecular Imaging Society, in collaboration with the Coalition of PET Drug Manufacturers. The organizing committee for the workshop consisted of representatives from academic and commercial PET manufacturers as well as FDA staff members. The coauthors on this paper are all members of the workshop-organizing committee.

The U.S. Food and Drug Administration's role in improving radiation dose management for medical X-ray imaging devices.

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.

Pediatric contrast-enhanced ultrasound: shedding light on the pursuit of approval in the United States.

For two decades, pediatric contrast US has been well accepted throughout Europe and other parts of the world outside the United States because of its high diagnostic efficacy and extremely favorable safety profile. This includes intravenous (IV) administration, contrast-enhanced US (CEUS) and the intravesical application, contrast-enhanced voiding urosonography (ceVUS). However, the breakthrough for pediatric contrast US in the United States did not come until 2016, when the U.S. Food and Drug Administration (FDA) approved the first pediatric indication for a US contrast agent. This initial approval covered the use of Lumason (Bracco Diagnostics, Monroe Township, NJ) for the evaluation of focal liver lesions via IV administration in children. A second pediatric indication followed shortly thereafter, when the FDA extended the use of Lumason for assessing known or suspected vesicoureteral reflux via intravesical application in children. Both initial pediatric approvals were granted without prospective pediatric clinical trials, based instead on published literature describing favorable safety and efficacy in children. Three years later, in 2019, the FDA approved Lumason for pediatric echocardiography following a clinical trial involving a total of 12 subjects at 2 sites. The story of how we achieved these FDA approvals spans more than a decade and involves the extraordinary dedication of two professional societies, namely the International Contrast Ultrasound Society (ICUS) and the Society for Pediatric Radiology (SPR). Credit also must be given to the FDA staff for their commitment to the welfare of children and their openness to compelling evidence that contrast US is a safe, reliable, radiation-free imaging option for our pediatric patients. Understanding the history of this approval process will impact the practical application of US contrast agents, particularly when expanding off-label indications in the pediatric population. This article describes the background of the FDA's approval of pediatric contrast US applications to better illuminate the potential pathways to approvals of future indications.

From Intention to Action: Operationalizing AGA Diversity Policy to Combat Racism and Health Disparities in Gastroenterology

From Intention to Action: Operationalizing AGA Diversity Policy to Combat Racism and Health Disparities in Gastroenterology

The US Food and Drug Administration Centers for Regulatory Science and Innovation: Current Activities and Future Promise to Accelerate Innovations.

The US Food and Drug Administration Centers for Regulatory Science and Innovation: Current Activities and Future Promise to Accelerate Innovations.

(Invited) A FDA Staff Perspective on Navigating the Regulatory Landscape and Moving Medical Devices to the Marketplace

The United States Food and Drug Administration (FDA) ensures that patients in the U.S. have access to safe and effective medical devices. The Division of Neurological and Physical Medicine Devices reviews medical devices that interface with the nervous system. This presentation will assist attendees in how to navigate the FDA’s regulatory landscape to successfully bring medical devices to patients.

Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction.

The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes.

The role of regulators, investigators, and patient participants in the rise of the placebo response in major depressive disorder.

The role of regulators, investigators, and patient participants in the rise of the placebo response in major depressive disorder.

The Food and Drug Administration and the Future of Drug Development for the Treatment of Diabetes.

The U.S. Food and Drug Administration (FDA) regulates the marketing of drugs in the United States. The FDA staff faces substantial challenges in evaluating preclinical and clinical trial data for a proposed new drug and deciding whether the resultant benefit-risk assessment supports marketing approval. Any approval decision will be associated with uncertainty regarding the drug's true risks and benefits because of the inherent limits of testing in pre-approval development programs, the sample sizes included in clinical trials, and the structured environment of clinical trials versus patterns of use in general clinical practice. Indeed, the only way to completely avoid the occurrence of unanticipated risks after drug approval would be to stop approving new drugs. How the FDA deals with this uncertainty in benefit-risk assessment will profoundly affect treatment options for people with diabetes and for the health care professionals who care for them. The challenges facing the FDA in the field of diabetes have been all too well illustrated in recent years. After many years of treating patients with a relatively limited pharmacological armamentarium, the past 20 years have witnessed the discovery of new drug targets and the development of new therapeutic options for people with diabetes. However, the risks of rapid advances have also become apparent. The introduction of thiazolidinediones was greeted with excitement because of their potential to change treatment paradigms. The subsequent withdrawal of troglitazone because of hepatotoxicity concerns made clear the potential hazards of early adoption of new drugs.1 In 2007, analyses suggesting that rosiglitazone increased cardiovascular event rates in people with type 2 diabetes2 caused concern among both patients and physicians. Subsequent publications and regulatory reviews motivated by the rosiglitazone analyses fundamentally changed the landscape for diabetes drug development. Cardiovascular events, including myocardial infarctions (MIs) and stroke, are major causes of mortality and …

Ketotifen in the management of chronic urticaria: resurrection of an old drug

Ketotifen is an oral antiallergic drug developed in 1970 by Sandoz Pharmaceuticals of Switzerland. It is a benzocycloheptathiophene derivative and was initially marketed as an inhibitor of anaphylaxis.1 The pharmacodynamic properties of ketotifen are many, because it is an inhibitor of the release and/or activity of mast cell and basophil mediators, including histamine, neutrophil, and eosinophil chemotactic factors, arachidonic acid metabolites, prostaglandins, and leukotrienes.2 Thus, it inhibits the bronchial response to inhaled histamine, allergen, or aspirin. In addition, the ocular, nasal, and dermal responses to applied allergen in sensitized patients are attenuated with use of ketotifen.3 It also has been found to have some calcium antagonist activity and to inhibit responses to platelet-activating factor from proinflammatory cells, such as eosinophils.2 Additional possible modes of action include its ability to reverse b2-agonisteinduced decreases in b-adrenoreceptor density and to alter the affinity of these receptors and increase intracellular concentrations of cyclic adenosine monophosphate.3 Ketotifen has a chemical structure similar to some first-generation antihistamines, such as cyproheptadine and azatidene.2 With regard to the pharmacokinetic properties of ketotifen, it is readily absorbed from the gastrointestinal tract after oral administration and achieves peak plasma concentrations within 2 to 4 hours of administration. Clearance of the drug from plasma is biphasic, with a half-life of distribution of 3 hours and a half-life of elimination of 22 hours in adults.3 However, the onset of action of ketotifen is slow, and it may take 4 to 6 weeks to achieve full prophylactic value under certain conditions.4 Ketotifen was originally patented by Sandoz in the 1970s. It became very popular for management of asthma in Japan and clinical trials were initiated in the United States in the 1980s for management of asthma and other allergic conditions. One author served on the Food and Drug Administration (FDA) Pulmonarye Allergy Drugs Advisory Committee and chaired that group from 1984 to 1986. Approval for treatment of asthma was not granted, but FDA staff did recommend more extensive evaluations for management of urticaria. Unfortunately, the latter studies have not been performed in a robust fashion. However, oral ketotifen has been used in patients with asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, chronic urticaria, cold-induced urticaria, cholinergic urticaria, exercise-induced urticaria, mastocytosis, and food allergy in Canada, Europe, and Mexico. Approval was granted for ocular administration in the United States for allergic conjunctivitis and later the drug became available over the counter. A review of clintrials.gov shows evaluations of ketotifen by oral administration for fibromyalgia, atopic dermatitis, attenuation of reactions during peanut desensitization, allergic rhinitis, asthma, and post-traumatic joint contractures. The authors became aware that ketotifen could be obtained in the United States from compounding pharmacies and began prescribing it more extensively in their clinics for severe urticaria in 2011. For adults and older children with asthma or allergic disease, the recommended dose of ketotifen is 1 mg twice daily. For young children 6 months to 3 years old, the recommended dose is 0.5 mg twice daily.3 It must be noted that oral ketotifen can be safely compounded in the United States. Pharmacy compounding is a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient. Pharmacy compounding, if performed properly, can serve an important public health need if a patient cannot be treated with an FDA-approved medication. The issue of safety of compounded drugs in the FDA Compliance Policy for Pharmacy Compounding is primarily for injectable drugs and does not relate to oral compounded drugs. This policy does include a select list of compounding drugs that were withdrawn or Reprints: Kristin C. Sokol, MD, MS, MPH, Division of Allergy and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555; E-mail: Kcsokol@utmb.edu. Disclosures: Authors have nothing to disclose. Funding Sources: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1T71) from the National Center for Advancing Translational Sciences, National Institutes of Health.

A new paradigm for obtaining marketing approval for pediatric-sized prosthetic heart valves

Congenital heart valve disease is one of the most common abnormalities in children. There are limited technological solutions available for treating children with congenital heart valve diseases. The aim of this study is to provide the details of the consensus reached in terms of pediatric definitions, design approach, invitro testing, and clinical trials, which may be used as guidance for developing prosthetic heart valves for the pediatric indication. In stark contrast to the various designs of adult-sized replacement valves available in the market, there are no Food and Drug Administration (FDA)-approved prosthetic heart valves available for use in the pediatric population. There is a pressing need for FDA-approved pediatric valve devices in the United States. The pediatric patient population has been typically excluded from replacement heart valve trials for several reasons. In January 2010, heart valve manufacturers and pediatric clinicians collaborated with academicians and FDA staff in a workshop to suggest ways to successfully evaluate pediatric prosthetic valves and conduct pediatric clinical trials to provide acceptable heart valve replacement options for this patient population. Recommendations, derived from ISO 5840:2005 and the 2010 FDA Draft Replacement Heart Valve Guidance, are provided for hydrodynamic, durability, and fatigue testing. The article specifically addresses invitro and premarket and postmarket approval clinical studies that should be considered by a heart valve manufacturer for obtaining regulatory approval of pediatric sizes of prosthetic heart valve designs that are already approved for adult clinical use.

Assessing the Benefit-Risk for New Drugs

The U.S. Food and Drug Administration (FDA) regulates which drugs can be marketed in the U.S. as well as their label requirements. A congressionally authorized advisory committee process allows the FDA to receive input from outside experts on important regulatory decisions (1). Further, the advisory committee process enhances transparency by allowing the public, including health care professionals, to understand the issues being considered. The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) “reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of endocrine and metabolic disorders, and makes appropriate recommendations to the Commissioner of Food and Drugs” (2). Operationally, the FDA’s Division of Metabolism and Endocrinology Products (DMEP) is responsible for the review of most drugs used for indications relevant to endocrinologists and coordinates the EMDAC’s meetings. In recent years, the EMDAC has been asked to review a number of controversial drugs, particularly those for the treatment of diabetes and obesity. Often the assessment of these drugs requires integration of preclinical and clinical data to formulate a benefit-risk assessment. The assessment of benefit-risk for drugs is increasingly recognized to be a challenging task, and formal tools have been proposed to make this process more effective (3–7). In contrast with the DMEP and other FDA staff, most EMDAC members will have limited experience in these types of integrative, complex evaluations. Further, EMDAC members will spend considerably less time evaluating the available data in comparison with DMEP staff. Thus, it seems important to compare the recommendations made by EMDAC with the subsequent marketing and label decisions to assess concordance between the evaluative approaches used by EMDAC and that of DMEP (DMEP will be used as shorthand for the full FDA’s involvement in regulatory decisions). At most of the EMDAC …

Pluripotent Stem Cells in Translation: A Food and Drug Administration-National Institutes of Health Collaboration

Recently, the U.S. Food and Drug Administration (FDA), the U.S. National Institutes of Health, and the stem cell research community have collaborated on a series of workshops that address moving pluripotent stem cell therapies into the clinic. The first two workshops in the series focused on preclinical science, and a third, future workshop will focus on clinical trials. This summary addresses major points from both of the recent preclinically focused meetings. When entering into a therapeutics developmental program based on pluripotent cells, investigators must make decisions at the very early stages that will have major ramifications during later phases of development. Presentations and discussions from both invited participants and FDA staff described the need to characterize and document the quality, variability, and suitability of the cells and commercial reagents used at every translational stage. This requires consideration of future regulatory requirements, ranging from donor eligibility of the original source material to the late-stage manufacturing protocols. Federal, industrial, and academic participants agreed that planning backward is the best way to anticipate what evidence will be needed to justify human testing of novel therapeutics and to eliminate wasted efforts.

A Roundtable Discussion: Home Healthcare—Not A Hospital in the Home

Home healthcare is vital for a large percentage of the population. According to data from the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control (CDC), 7 million people in the United States receive home healthcare annually. The use of medical devices in the home and other nonclinical environments is increasing dramatically. By the year 2050, an estimated 27 million people will need continuing care in the home or in the community and not in a controlled clinical environment. 1 The FDA recently announced its Home Use Devices Initiative and issued the document, "Draft Guidance for Industry and FDA Staff-Design Considerations for Devices Intended for Home Use" on Dec. 12, 2012. 2 The Center for Devices and Radiological Health (CDRH) regulates medical devices, but that regulatory authority alone is not enough to ensure safe and effective use of devices in the home. To address these and other issues, AAMI and FDA will co-host a summit on healthcare technology in nonclinical settings Oct. 9-10, 2013.

Side-effects of roflumilast

Two articles1,2 published in The Lancet in 2009 on roflumilast for chronic obstructive pulmonary disease (COPD) describe four clinical studies (M2-124, M2-125, M2-127, and M2-128) done by the drug company that owns the patent on roflumilast. The raw data on the condition of patients who participated in the studies is not available to anyone outside of the company or the US Food and Drug Administration (FDA). Since roflumilast was approved by the FDA, new information about the side-effects has come to light, from independent analysis of these data by FDA staff physicians.

The US Food and Drug Administration's Sentinel Initiative: Expanding the horizons of medical product safety

The US Food and Drug Administration's Sentinel Initiative: Expanding the horizons of medical product safety

“Research Use Only” Reagents: Is There an Imperative for Increased FDA Oversight?

On June 1, 2011, the US Food and Drug Administration (FDA)2 Office of In Vitro Diagnostic Device Evaluation and Safety issued draft guidance for industry and FDA staff intended to provide guidance regarding the FDA's thinking about in vitro diagnostic device (IVD) products labeled for “Research Use Only” (RUO) or “Investigational Use Only” (IUO) (1). Reagents may be marketed under either of these labels without FDA premarket review and are partially or totally exempt from compliance with the Quality Systems Regulation (21 CFR 820). Therefore, an IVD manufacturer might it very tempting to avoid the trouble and expense of a 510(k) or premarket-approval submission by labeling a product as RUO or IUO, despite knowing full well that the product is likely being used as an IVD under conditions in which there is no research protocol and no oversight by an institutional review board. There is no doubt that the FDA's intent is to improve patient safety. Compliance with the Quality Systems Regulation provides assurance that an IVD meets manufacturing specifications and that lot-to-lot variations are minimized and well understood. FDA clearance provides further assurance that the performance characteristics of laboratory tests are sufficiently well understood as to enable their intelligent use. Furthermore, the use by clinical laboratories of FDA-cleared IVD products likely reduces interlaboratory variation in testing and increases the ease with which results can be “ported” from one healthcare facility to another, potentially reducing healthcare costs that arise from duplicate testing. Nevertheless, the laboratory community is right to be concerned about the guidance document statement that manufacturers should not sell RUO or IUO reagents “to laboratories that they know use the product for clinical diagnostics use.” This statement could have unintended consequences that adversely affect patient care. In particular, the molecular diagnostics community has expressed concern that such …