Food And Drug Administration 's Center Research Articles

First Person: Howard Koh, MD, MPH: Physician devotes his career to improving public health on many fronts.

First Person: Howard Koh, MD, MPH: Physician devotes his career to improving public health on many fronts.

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.

Concerns over increased vaping in schoolchildren

Concerns over increased vaping in schoolchildren

Experts Call For More Action to Thwart Youth Vaping ‘Epidemic’

Experts Call For More Action to Thwart Youth Vaping ‘Epidemic’

Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings

Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years. To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016. In this quality improvement study, data were extracted from the FDA's Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017. From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments. Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.

Advancing Regulatory Science With Computational Modeling for Medical Devices at the FDA's Office of Science and Engineering Laboratories.

Protecting and promoting public health is the mission of the U.S. Food and Drug Administration (FDA). FDA's Center for Devices and Radiological Health (CDRH), which regulates medical devices marketed in the U.S., envisions itself as the world's leader in medical device innovation and regulatory science–the development of new methods, standards, and approaches to assess the safety, efficacy, quality, and performance of medical devices. Traditionally, bench testing, animal studies, and clinical trials have been the main sources of evidence for getting medical devices on the market in the U.S. In recent years, however, computational modeling has become an increasingly powerful tool for evaluating medical devices, complementing bench, animal and clinical methods. Moreover, computational modeling methods are increasingly being used within software platforms, serving as clinical decision support tools, and are being embedded in medical devices. Because of its reach and huge potential, computational modeling has been identified as a priority by CDRH, and indeed by FDA's leadership. Therefore, the Office of Science and Engineering Laboratories (OSEL)—the research arm of CDRH—has committed significant resources to transforming computational modeling from a valuable scientific tool to a valuable regulatory tool, and developing mechanisms to rely more on digital evidence in place of other evidence. This article introduces the role of computational modeling for medical devices, describes OSEL's ongoing research, and overviews how evidence from computational modeling (i.e., digital evidence) has been used in regulatory submissions by industry to CDRH in recent years. It concludes by discussing the potential future role for computational modeling and digital evidence in medical devices.

Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016

A critical question in health care is the extent of scientific evidence that should be required to establish that a new therapeutic agent has benefits that outweigh its risks. Estimating the costs of this evidence of efficacy provides an important perspective. To estimate costs and assess scientific characteristics of pivotal efficacy trials that supported the approval of new therapeutic agents by the US Food and Drug Administration (FDA) from 2015 to 2016. This study identified 59 novel therapeutic drugs using the annual summary reports from the FDA Center for Drug Evaluation and Research. ClinicalTrials.gov, FDA reviews, and peer-reviewed publications that were publicly available in 2017 were used to identify 52 characteristics of each efficacy trial. Costs were calculated with a global clinical trial cost assessment tool available to contract research organizations and pharmaceutical sponsors. Estimated mean cost and 95% CIs based on industry benchmark data from 60 countries. Measures of trials' scientific characteristics included trial design (no control group, placebo, and active drug), end point (surrogate outcome, clinical scale, and clinical outcome), patient enrollment, and treatment duration. A total of 138 pivotal clinical trials provided the basis for approval of 59 new therapeutic agents by the FDA from 2015 to 2016, with a median estimated cost of $19.0 million (interquartile range, $12.2 million-$33.1 million). Estimated costs ranged from less than $5 million for trials without a control group for 3 orphan drugs with fewer than 15 patients each to $346.8 million (95% CI, $252.0 million-$441.5 million) for a noninferiority trial with end points assessing clinical benefit. Twenty-six of 138 trials (18.8%) were uncontrolled, with a mean estimated cost of $13.5 million (95% CI, $10.1 million-$16.9 million). Trials designed with placebo or active drug comparators had an estimated mean cost of $35.1 million (95% CI, $25.4 million-$44.8 million). Costs also varied by trial end point, treatment duration, patient enrollment, and therapeutic area. The highest-cost trials were those in which the new agent had to be proved to be noninferior with clinical benefit end points compared with an agent already available or those that required larger patient populations to achieve statistical power to document smaller treatment effects or accrue infrequently occurring end points.

Interpreting the Regulatory Perspective on Adaptive Designs

ABSTRACTThe Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) released a draft guidance (DG) on adaptive clinical trials (ACT) for drugs and biologics in February, 2010. In May, 2016, FDA Center for Devices and Radiological Heath (CDRH) and CBER issued the final guidance (FG) on adaptive medical device trials. The purpose of the FG is to provide clarity on how to plan and implement adaptive designs (AD) for clinical studies used in medical device development and to further encourage companies to use AD.While both the device FG and drug and biologics DG provided positive review of ACT, the FG position was stronger, stating that the FDA centers “further encourage companies to consider the use of AD in their clinical trials.” Both guidances emphasize the importance of preplanning to avoid Type I error inflation, strict following of the plan to minimize operational bias, and frequent and early interactions with the FDA to ensure the success of the planned ACT. Both guidances emphasize the utilities of clinical trial simulations in design of ACT and in analysis of adaptive trial data. In this article, we present our understanding the guidances.

Clinical Trial End Points for Hemodialysis Vascular Access: Background, Rationale, and Definitions.

Hemodialysis vascular access is the “lifeline” for patients on hemodialysis. Unfortunately, because of its poor patency and significant complication rate, it is also the “Achilles heel” of hemodialysis. For example, the current unassisted arteriovenous fistula (AVF) maturation rate is only

Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.

The Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary supplements, and cosmetic products. To present a descriptive analysis of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act as pertaining to dietary supplements adverse events reporting. We queried CAERS for data from the 2004-2013 AERs specifying at least 1 suspected dietary supplement product. We extracted the product name(s), the symptom(s) reported, age, sex, and serious adverse event outcomes. We examined time trends for mandatory and voluntary reporting and performed analysis using SAS v9.4 and R v3.3.0 software. Of the total AERs (n = 15 430) received from January 1, 2004, through December 31, 2013, indicating at least 1 suspected dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9% were both mandatory and voluntary. Reported serious outcomes included death, life-threatening conditions, hospitalizations, congenital anomalies/birth defects and events requiring interventions to prevent permanent impairments (5.1%). The dietary supplement adverse event reporting rate in the United States was estimated at ~2% based on CAERS data. This study characterizes CAERS dietary supplement adverse event data for the 2004-2013 period and estimates a reporting rate of 2% for dietary supplement adverse events based on CAERS data. The findings show that the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act had a substantial impact on the reporting of adverse events.

Representation of Women and Minorities in Clinical Trials for New Molecular Entities and Original Therapeutic Biologics Approved by FDA CDER from 2013 to 2015.

The U.S. Food and Drug Administration (FDA) has made efforts to encourage adequate assessment of women, racial/ethnic minorities, and geriatric participants in clinical trials through regulations and guidance documents. This study surveyed the demographics of clinical trial participants and the presence of efficacy and safety analyses by sex for new drugs approved between 2013 and 2015 by the FDA Center for Drug Evaluation and Research. New drug marketing applications submitted to FDA were surveyed for demographic data (sex, race, ethnicity, and age) and the presence of sex-based analyses for efficacy and safety. The Ratio of the Proportion of women in clinical trials for the indicated disease population relative to the estimated Proportion of women in the disease population (PPR) was calculated for new drug indications. Of the 102 new drugs in this cohort (defined as new molecular entity drugs and original therapeutic biologics), sex was reported for >99.9% of trial participants, and women accounted for 40.4% of these participants. An estimated 77.2% of participants were White, 6.4% were Black/African American, and 29.1% were aged ≥65 years. Sex-based analyses for both efficacy and safety were conducted for 93.1% of applications. PPR was calculated for 82 new drugs for a total of 60 indications, of which 50 indications (83.3%) had a PPR ≥0.80. Sex data are now collected for almost all study participants, and this study shows appropriate sex participation for most new drugs when estimated disease prevalence by sex (PPR) is considered. Therapeutic area and disease indication are important considerations when assessing the sex of participants because variation occurs depending on the disease under study. Some racial minorities, especially Blacks/African Americans, are still not well represented in most drug development programs and remain an area where improvement is needed.

Abstract SY01-03: Reducing harm by targeting the addictiveness of combusted tobacco products through regulated reductions in nicotine content

Abstract Nicotine is the primary addictive constituent in cigarettes, driving chronic dependent use in millions of Americans. Approximately half of those individuals will die as a result of smoking unless they quit. One strategy for greatly reducing the harm caused by smoking is to limit the nicotine content of cigarettes and other combusted tobacco products to levels that are less addictive. This approach differs from so-called “light” and “ultralight” cigarettes, which have nicotine content similar to full-flavored cigarettes; light cigarettes reduce machine-measured nicotine yield as a consequence of ventilation, a design feature that smokers can easily overcome (e.g., by inhaling larger volumes) to maintain high levels of nicotine exposure. True regulated reductions in nicotine content became possible in 2009 when the Family Smoking Prevention and Tobacco Control Act gave the U.S. Food and Drug Administration (FDA) the authority to reduce (but not eliminate) the nicotine in tobacco products. Consequently, the FDA and NIH are supporting a large portfolio of research aimed at evaluating the potential public health impact of product standards that would reduce the nicotine content of cigarettes. This presentation focuses primarily on recent randomized clinical trials in which participants are provided investigational cigarettes with varying levels of nicotine and followed over weeks to months to assess the potential benefits and risks of regulated reductions in nicotine. These studies indicate that reducing the nicotine content of cigarettes by approximately 85% or more leads to fewer cigarettes smoked per day, reduced nicotine exposure, and/or reduced nicotine dependence with little evidence of compensatory smoking or other unintended consequences. In addition, preclinical data from rat models of nicotine self-administration indicate that nicotine reduction would likely also decrease the initiation of use among nicotine-naïve adolescent users. These data, if supported by other ongoing trials, raise critically important questions about whether and how a product standard that limits the nicotine content of all combusted tobacco products might be promulgated to reduce the harms associated with smoking. Further discussion of this approach and how it might interact with the rapidly changing landscape of tobacco products (e.g., e-cigarettes) should be a high priority for all those interested in the prevention of tobacco-related disease. Funding: Research reported in this presentation was supported by the National Institute on Drug Abuse and FDA Center for Tobacco Products (CTP) (U54 DA031659). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. Citation Format: Eric Donny. Reducing harm by targeting the addictiveness of combusted tobacco products through regulated reductions in nicotine content [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY01-03. doi:10.1158/1538-7445.AM2017-SY01-03

Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation.

Ten-Year Experience for the Center for Drug Evaluation and Research, Part 2: FDA's Role in Ensuring Patient Safety.

The purpose of this study was to describe the role of the US Food and Drug Administration (FDA) in ensuring the safety of patients receiving investigational drugs under expanded access. To better define FDA's role in the review of requests for expanded access, multiple queries of FDA's Center for Drug Evaluation and Research (CDER) document tracking system were performed. The queries identified reasons for, and outcomes of, expanded access requests for investigational drugs that were either not allowed to proceed or denied over a 10-year time period. An in-depth review of a random sample of single-patient, non-emergency investigational new drug (IND) applications that were allowed to proceed was also conducted. Overall, 99.3% of the applications for almost 9000 expanded access of an investigational drug were allowed to proceed. There were 62 requests that were either denied (38 emergency INDs) or not allowed to proceed (24 non-emergency INDs). The most common reasons for denying emergency INDs was that the patient was stable on current therapy and that it was not deemed an emergency. The most common reasons for not allowing non-emergency expanded access INDs to proceed were incomplete application, unsafe dosing, demonstrated lack of efficacy for intended use, availability of adequate alternative therapies, and inadequate information provided in the application on which to base a decision. A review of a random sample of 150 single-patient, non-emergency INDs revealed that FDA recommended changes to dosing, safety monitoring, or informed consent in 11%. FDA plays a significant role in the protection of patients who receive investigational drugs under expanded access. An extremely small percentage of applications received are not allowed to proceed; however, FDA provides significant input based on information that may not be available to treating physicians in order to ensure patient safety under the applications that do proceed.

Innovative postmarket device evaluation using a quality registry to monitor thoracic endovascular aortic repair in the treatment of aortic dissection

ObjectiveUnited States Food and Drug Administration (FDA)-mandated postapproval studies have long been a mainstay of the continued evaluation of high-risk medical devices after initial marketing approval; however, these studies often present challenges related to patient/physician recruitment and retention. Retrospective single-center studies also do not fully represent the spectrum of real-world performance nor are they likely to have a sufficiently large enough sample size to detect important signals. In recent years, The FDA Center for Devices and Radiological Health has been promoting the development and use of patient registries to advance infrastructure and methodologies for medical device investigation. The FDA 2012 document, “Strengthening the National System for Medical Device Post-market Surveillance,” highlighted registries as a core foundational infrastructure when linked to other complementary data sources, including embedded unique device identification. The Vascular Quality Initiative (VQI) thoracic endovascular aortic repair for type B aortic dissection project is an innovative method of using quality improvement registries to meet the needs of device evaluation after market approval. Here we report the organization and background of this project and highlight the innovation facilitated by collaboration of physicians, the FDA, and device manufacturers. MethodsThis effort used an existing national network of VQI participants to capture patients undergoing thoracic endovascular aortic repair for acute type B aortic dissection within a registry that aligns with standard practice and existing quality efforts. The VQI captures detailed patient, device, and procedural data for consecutive eligible cases under the auspices of a Patient Safety Organization (PSO). Patients were divided into a 5-year follow-up group (200 acute; 200 chronic dissections) and a 1-year follow-up group (100 acute; 100 chronic). The 5-year cohort required additional imaging details, and the 1-year group required standard VQI registry data entry. ResultsThe sample size of patients in each of the 5-year acute and chronic dissection arms was achieved ≤24 months of project initiation, and data capture for the 1-year follow-up group is also nearly complete. Data completeness and follow-up has been excellent, and the two FDA-approved devices for dissection are equally represented. ConclusionsAlthough the completeness of long-term follow-up is yet to be determined, the rapidity of data collection supports the use of this construct for device assessment after market approval. The alignment of this effort with routine clinical practice and ongoing quality improvement initiatives is critical and has required minimal additional effort by practitioners, thus facilitating patient inclusion. Importantly, the success and development of this unique project has helped inform FDA strategy for future device evaluation after market approval.

Case Study for Lean Management in the Public Sector: Improving Combination Product Review at the Food & Drug Administration.

Therapeutics known as combination products because they combine drug, device, and/or biologic elements can offer important advantages relative to single‐modality products. However, regulatory policy in this arena has lagged relative to increases in product submissions and complexity of these products. In this article we describe how the US Food and Drug Administration (FDA) applied Lean Management methods to improve and streamline the process by which different FDA centers and offices coordinate review of combination products. Therapeutic products that combine drug, device, and/or biologic elements account for an increasing share of medical products. The global market for these combination products is expected to grow at a compound annual rate of 5.6% from 2012–2017,1 higher than rates projected for medical devices2 or prescription drugs.3 Combination products such as drug‐eluting stents, prefilled infusion pumps and inhalers, transdermal patches, antibody‐drug conjugates, and even some digital health technologies comprise approximately one‐third of all medical products under development.4 Combination product submissions to the FDA including new technologies increased 17% in 2015 vs. the previous 5‐year average. Combination products offer potential advantages relative to single‐modality products, including fewer adverse effects, improved adherence, controlled drug release, and targeted delivery. However, regulatory policies have not kept pace with the growing number and complexity of these products.5

Asociaciones de pacientes y autorización de nuevos fármacos en Estados Unidos. El caso del eteplirseno para la distrofia muscular de Duchenne

In 2016 the US Food and Drug Administration (FDA) granted the marketing authorization for eteplirsen for Duchenne muscular dystrophy. This has been a very controversial decision since it happened after a negative assessment from both the Advisory Committee and the technical FDA evaluation team. The FDA's Center for Drug Evaluation and Research (CDER) director was who ultimately approved the product, while the FDA Commissioner did not overrule that decision. To report about the most relevant events regarding the approval of eteplirsen by the US FDA. All relevant facts that occurred during the clinical development and evaluation phase following 'accelerated approval' procedure of eteplirsen are discussed in detail. The technical FDA evaluation team reasons supporting that the drug has not proven clinical benefit, the attitude of patient advocacy groups and the post-approval FDA requirements to the marketing authorization holder are discussed. Finally, we reflect on what is the situation Spanish patients face once eteplirsen is on the US market. This is a unique case in the history of drug authorizations in western countries, that shows the difficulties that current regulations on accelerated approval of new medicines could have when interpreting scarce and low quality clinical development data, when dealing with rare diseases with no available therapies.

US Prescription Drug User Fee Act (PDUFA): An Introduction for the Pharmaceutical Physician

Originally enacted to address the delays in US Food and Drug Administration (FDA) new drug review due to chronic understaffing and outdated systems, the Prescription Drug User Fee Act (PDUFA) of 1992, with its 5-year reauthorization cycle, enabled rapid rigorous review and ushered in a new era of continuing program innovation, evaluation, and improvement. This has resulted in a scientifically and financially strong program with transparent stakeholder engagement as a routine way of doing business. The enhancements to the process of human drug review, conducted in the FDA Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), originally focused on the FDA review of a new drug application, have evolved and expanded to include extensive communication and consultation between drug sponsors and FDA throughout drug development, advances in regulatory science applied to drug development and regulatory oversight, strengthening and innovating approaches to post-market safety, increasing patient focus and modernizing supporting informatics. These enhancements, identified and supported in successive rounds of user fee negotiation with regulated industry, have enabled the USA to sustain global leadership in drug innovation, and earlier patient access to safe and effective new medicines.

Abstract CT121: Demographics of clinical trial participants for new molecular entity (NME) oncology drugs and biologics approved by FDA CDER in 2015

Abstract Background: In 2015, approximately 810,100 new cancer cases were diagnosed in females in the US. To facilitate the assessment of efficacy and safety of medical products in the diverse populations who might use them after approval, the Food and Drug Administration (FDA) has implemented guidance and regulations to encourage greater participation of women and minorities in clinical trials (CTs). Objectives: To assess demographics in oncology CTs submitted in support of “new drugs” (i.e., New Molecular Entity New Drug Applications (NME NDAs) and original Biologics License Applications (BLAs)) approved by the FDA's Center for Drug Evaluation and Research (CDER) in 2015. Methods: Participation by sex, race, and age (<65 years, ?65 years) and presence of sex-based efficacy and safety analyses were assessed from sponsors’ final clinical study reports for new oncology drugs for adult indications approved in 2015. Sex-based analyses were coded as exploratory or conclusive as previously reported., Results: Fourteen new oncology drugs were approved by CDER in 2015. One BLA and one NDA were excluded from the analysis because they were for pediatric or sex-specific indications. For the 12 remaining drugs, there were 188 trials (phase 1, 2, or 3) that included a total of 17,702 subjects, 48.1% of whom were women. Of the subjects for which race was reported (94.2% of the total), 78.0% were Caucasian, and of those for which age group was reported (75.3% of all subjects), 33.4% were ?65 years of age. Women were 43.1%, 53.2%, and 53.9% of subjects in phase 1, 2, and 3 CTs, respectively. PPR, defined as the Ratio of the Proportion of women in the indicated disease population in the CTs to the Proportion of women in the disease population, was ?0.8 for 11 new drugs and <0.8 for one new drug. Eleven new drugs included both efficacy and safety sex-based analyses, and one new drug included only efficacy sex-based analysis. Conclusions: Relative to their proportion in the disease population, female participation was comparable to (i.e., PPR between 0.8 and 1.2) or greater than men's in late-phase trials for 11 of the 12 oncology drugs examined. Female participation in early-phase CTs was lower than in late-phase CTs; however, late-phase clinical trials are typically where FDA's risk-benefit assessments are made. Citation Format: Hilary Wright, Merina Elahi, Ayomide Igun, Greg Soon, Alice Chen, Anne Pariser, Emmanuel Fadiran. Demographics of clinical trial participants for new molecular entity (NME) oncology drugs and biologics approved by FDA CDER in 2015. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT121.

Perspective on Advancing FDA Regulatory Monitoring for Mycotoxins in Foods using Liquid Chromatography and Mass Spectrometry (Review).

The presence of mycotoxins (such as aflatoxins, deoxynivalenol, fumonisins, and patulin) is routinely monitored by the U.S. Food and Drug Administration (FDA) to ensure that their concentrations in food are below the levels requiring regulatory action or advisories. To improve the efficiency of mycotoxin analysis, the researchers at the FDA's Center for Food Safety and Applied Nutrition have been evaluating modern LC-MS technologies. Consequently, a variety of LC-tandem MS and LC-high-resolution MS methods have been developed, which simultaneously identify and quantitate multiple mycotoxins in foods and feeds. Although matrix effects (matrix-induced ion suppression or enhancement) associated with LC-MS-based mycotoxin analysis remain, this review discusses methods for managing these effects and proposes practical solutions for the future implementation of LC-MS-based multimycotoxin analysis.