Drug Administration Regulations Research Articles

US researchers call for FDA action to avoid another EVALI outbreak.

Researchers are calling for tighter US Food & Drug Administration (FDA) regulation of vaping products to avoid another outbreak of e-cigarette or vaping product use-associated lung injury (EVALI). EVALI hospitalised thousands of Americans starting in 2019, most of them teenagers or young adults, leaving many survivors with damaged lungs and persisting pulmonary dysfunction.

Customizable document control solution for 3D printing at the point-of-care

BackgroundThe rapid expansion and anticipated U.S Food and Drug Administration regulation of 3D printing at the point-of-care necessitates the creation of robust quality management systems. A critical component of any quality management system is a document control system for the organization, tracking, signature collection, and distribution of manufacturing documentation. While off-the-shelf solutions for document control exist, external programs are costly and come with network security concerns. Here, we present our internally developed, cost-effective solution for an electronic document control system for 3D printing at the point-of-care.MethodsWe created a hybrid document control system by linking two commercially available platforms, Microsoft SharePoint and Adobe Sign, using a customized document approval workflow.ResultsOur platform meets all Code of Federal Regulations Title 21, Part 11 guidances.ConclusionOur hybrid solution for document control provides an affordable system for users to sort, manage, store, edit, and sign documents. The system can serve as a framework for other 3D printing programs to prepare for future U.S Food and Drug Administration regulation, improve the efficiency of 3D printing at the point-of-care, and enhance the quality of work produced by their respective program.

Promoting Health Equity through Improved Regulation of Artificial Intelligence Medical Devices

Existing health disparities in the United States are partially driven by the way healthcare is delivered. There is interest in using Artificial Intelligence (AI)-driven software as medical devices (SaMD) to aid in healthcare delivery and reduce health disparities. However, AI-driven tools have the potential to codify bias in healthcare settings. Some AI-driven SaMDs have displayed substandard performance among racial and ethnic minorities. Auditing these tools for biased output can help produce more equitable outcomes across populations. However, there are currently no explicit Food and Drug Administration (FDA) regulations that examine bias in AI software in healthcare. Therefore, we propose the FDA develop a distinct regulatory process for AI-driven SaMDs that includes assessing equitable output across populations and avoiding potential health disparity exacerbation. This change could help prevent AI-driven health disparities nationwide.

Artificial Intelligence Algorithms in Health Care: Is the Current Food and Drug Administration Regulation Sufficient?

Given the growing use of machine learning (ML) technologies in health care, regulatory bodies face unique challenges in governing their clinical use. Under the regulatory framework of the Food and Drug Administration, approved ML algorithms are practically locked, preventing their adaptation in the ever-changing clinical environment, defeating the unique adaptive trait of ML technology in learning from real-world feedback. At the same time, regulations must enforce a strict level of patient safety to mitigate risk at a systemic level. Given that ML algorithms often support, or at times replace, the role of medical professionals, we have proposed a novel regulatory pathway analogous to the regulation of medical professionals, encompassing the life cycle of an algorithm from inception, development to clinical implementation, and continual clinical adaptation. We then discuss in-depth technical and nontechnical challenges to its implementation and offer potential solutions to unleash the full potential of ML technology in health care while ensuring quality, equity, and safety. References for this article were identified through searches of PubMed with the search terms "Artificial intelligence," "Machine learning," and "regulation" from June 25, 2017, until June 25, 2022. Articles were also identified through searches of the reference list of the articles. Only papers published in English were reviewed. The final reference list was generated based on originality and relevance to the broad scope of this paper.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, anddeveloping and enforcing regulatory standards for all e-cigarettes.

Current state of mobile health apps in endourology: a review of mobile platforms in marketplaces and literature.

Several mobile healthcare (mHealth) apps are available in various marketplaces, but there is still concern about their accuracy, data safety, and regulation. The goal of this review was to critically analyze the mobile apps created for education, diagnosis, and medical and surgical treatment of patients with kidney stone disease (KSD), as well as to assess the level of data security, the contribution of physicians in their development and adherence to the Food and Drug Administration (FDA) and Medical Device Regulation (MDR) guidance. A comprehensive literature search was performed using PubMed (September 2022), in the Apple App Store and Google Play store using relevant keywords and inclusion criteria. Information was extracted for the name of the app, primary and additional functionalities, release and last update, number of downloads, number of marks and average rating, Android/iOS compatibility, initial and in-app payments, data safety statement, physician involvement statement, and FDA/MDR guidance. A total of 986 apps and 222 articles were reviewed, of which based on the inclusion, 83 apps were finally analyzed. The apps were allocated to six categories about their primary purpose: education (n = 8), fluid trackers (n = 54), food content description and calculators (n = 11), diagnosis (n = 3), pre- and intra-operative application (n = 4), and stent trackers (n = 2). Of these apps, the number of apps supported for Android, iOS, and both of them were 36, 23, and 23, respectively. Despite a wide range of apps available for KSD, the participation of doctors in their development, data security, and functionality remains insufficient. Further development of mHealth should be carried out properly under the supervision of urological associations involving patient support groups, and these apps must be regularly updated for their content and data security.

United States Food and Drug Administration Regulation of Human Cells, Tissues, and Gene Therapies.

Research and development of gene therapies and cell- or tissue-based therapies has experienced exponential growth in recent decades and the potential for these products to treat diverse, often rare, clinical indications is promising. The Office of Therapeutic Products (OTP) in the Center for Biologics Evaluation and Research (CBER) at the United States Food and Drug Administration (US FDA) is responsible for the regulation of these products, among others, throughout the entire product lifecycle. This chapter provides an overview of the science- and data-driven approach to US FDA regulatory oversight of cell and genetherapy (CGT) products to ensure their safety and efficacy.

The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines.

This work gives a brief overview of carrier materials currently used in pharmaceutical studies on the three-dimensional (3D) semi-solid extrusion (SSE) printing of medicines for pediatrics. The suitability of using these carrier materials in pediatric formulations, concerning safety and toxicity, was reviewed by consulting the 'Safety & Toxicity of Excipients for Pediatrics' (STEP) database and the Food and Drug Administration (FDA) regulations. In the second part of this work, carrier materials were tested on their ability to form a semi-solid mixture with lactose by dual asymmetric centrifugation (DAC) and printing by SSE. With the combination of theoretical and experimental studies, this work will guide research toward grounded decision-making when it comes to carrier material selection for pharmaceutical pediatric 3D SSE printing formulations.

THE POTENTIAL CLINICAL AND ECONOMIC IMPACTS OF OVER-THE-COUNTER HEARING AIDS IN THE UNITED STATES

Abstract Food and Drug Administration regulations (released 8/16/22) for over-the-counter (OTC) hearing aids (HAs) allow the purchase of OTC HAs for adults with perceived mild-to-moderate hearing loss. Given this new development, the quality-of-life benefits and costs of OTC devices are now relevant but also unknown. We sought to project the population-level costs and effectiveness of US OTC HA provision. We used a microsimulation of hearing loss (DeciBHAL-US) to simulate: 1) traditional HA provision validated to published estimates of HA uptake (10-year delay), and 2) OTC HA provision for persons with perceived mild-to-moderate hearing loss at increased uptake rates (5-year delay) across quality-of-life and cost combinations. Simulated adults experienced probabilities of hearing loss (0.1–10%/year), subsequent age- and severity-dependent HA uptake (traditional HAs: 0.5–8%/year; OTC HAs: 1–16%/year) and discontinuation (4–13%/year). Utility benefit for traditional HAs was +0.11, and was +0.05–0.11 for OTC HAs. Costs included traditional HA uptake ($3,690; maintenance=$1,000/year) and OTC HA uptake ($600-$2,000; maintenance=$220–500/year). Our model projected lifetime discounted quality-adjusted-life-years (QALYs) for traditional HAs of 18.140/person, and 18.139–18.174/person for OTC HAs varying with utility benefit (+0.05–0.11). As long as OTC HA utility benefit was >+0.05, increased access resulted in higher QALYs and was cost-effective ($4,000/QALY-$92,500/QALY, varying with HA cost and utility benefit). Our results were sensitive to variations in OTC HA uptake rates. In conclusion, OTC HAs may increase population health and access to hearing healthcare in a cost-effective manner, and our model may continue to explore the costs and benefits of OTC HAs as pricing and evidence evolves.

Peltzman Revisited: Quantifying 21st-Century Opportunity Costs of Food and Drug Administration Regulation

Peltzman’s work is revisited in light of two recent opportunities to quantitatively assess trade-offs in drug regulation. First, reduced regulatory barriers to drug manufacturing associated with the 2017 reauthorization of generic-drug user fee amendments were followed by more entry and lower prices for prescription drugs. A simple, versatile industry model and historical data on entry indicate that easing restrictions on generics discourages innovation, but this cost is more than offset by benefits from enhanced competition, especially after 2016. Second, accelerated vaccine approval in 2020 had unprecedented net benefits as it improved health and changed the trajectory of the wider economy. Evidence suggests that cost-benefit analysis of Food and Drug Administration (FDA) regulation is incomplete without accounting for substitution toward potentially unsafe and ineffective treatments that are outside FDA jurisdiction and heavily utilized before FDA approval. Moreover, the policy processes initiating the regulatory changes show an influence of Peltzman’s findings. Consumer losses from purchases of ineffective drugs or hastily marketed unsafe drugs appear to have been trivial compared to gains from innovation. (Peltzman 1974, p. 82)

ICH and US-FDA validated HPTLC methods with greenness assessments for the assay of mixtures prescribed in stroke prophylaxis: application to pharmaceutical preparations and human plasma

The importance of the binary mixtures of the novel oral anticoagulants (NOACs): apixaban (APX), edoxaban tosylate (EDX) and rivaroxaban (RIV) with the lipid-lowering statin, rosuvastatin calcium (ROS) is highly emerging to save lives of cardiovascular patients as these combinations are used in prophylaxis from stroke. A high-performance thin-layer chromatography (HPTLC) method was developed for the quantitative assay of these life-saving mixtures in tablets and human plasma. Two mobile phases were developed for the assay in bulk and tablets; the first one: toluene‒ethyl acetate‒methanol‒25% ammonia (3.5:4.5:2:0.2, V/V) (method I) used for the three mixtures, and the second one: methanol‒25% ammonia (9.95:0.05, V/V) (method II) used for EDX/ROS mixture only. For analysis in human plasma, APX was used as internal standard in RIV/ROS and EDX/ROS mixtures using methods I and II, respectively, while RIV was used as internal standard in APX/ROS mixture using method I; the methods were validated according to the Food and Drug Administration (FDA) regulation for analysis in biological fluids. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in the presence of dosage form excipients and in the presence of plasma interferences (analysis in biological fluid) at single wavelength (291 nm) by use of the internal standard.

Racial Diversity and Reporting in United States Food and Drug Administration Registration Trials for Thoracic Malignancies from 2006 to 2020

There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006 to 2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

Liquid Nicotine, E-Cigarettes, and Vaping: Information for the Pediatric Emergency Medicine Provider.

E-cigarettes, or electronic cigarettes, are electronic nicotine delivery systems that are marketed as a healthier alternative to tobacco cigarettes. There has been an exponential increase in their use among youth since their introduction to the United States market in 2007. With increased use and popularity, there has been an increase in calls to poison control centers regarding liquid nicotine toxicity in children and adolescents. Recent US Food and Drug Administration and other federal regulations of e-cigarettes have attempted to limit availability to youth. This article reviews trends in e-cigarette use among youth, the background and mechanism of action of e-cigarettes, liquid nicotine toxicity, management of liquid nicotine toxicity, and recent policy updates regarding e-cigarettes.

Quantification of Cannabis in Infused Consumer Products and Their Residues on Skin.

Cannabis consumer products are a $4.6 billion industry in the U.S. that is projected to exceed $14 billion by 2025. Despite an absence of U.S. Food and Drug Administration (FDA) regulation or clinical data, thousands of nutraceuticals, topical consumer products, and beauty products claim benefits of hemp or cannabidiol. However, a lack of required quality control measures prevents consumers from knowing the true concentration or purities of cannabis-labeled products. Thirteen over-the-counter consumer products were examined for the presence of cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), and Δ9-tetrahydrocannabinolic acid A (THCA). Additionally, the efficacy of topical applications was investigated using a porcine skin model, in which particle size and zeta potential relate to skin permeability. Skin permeation was correlated to particle size and relative stability in skin-like conditions but not directly related to the CBD content, suggesting that topical products can be designed to enhance overall skin permeation. Of the products analyzed, all products have some traceable amount of cannabinoids, while seven products had multiple cannabinoids with quantifiable amounts. Overall, the need for further regulation is clear, as most products have apparent distinctions between their true and labeled contents.

Limitations of the new ISO standard for health and wellness apps

Limitations of the new ISO standard for health and wellness apps

Highlights on the Labels of Packaged Foods Sold in Jordanian Market from A Cross-Sectional Study

Jordan has adapted a strategy to prevent chronic diseases. Accordingly, Ministry of Health is looking for controlling food labeling particularly food fat, trans-fat, and caloric content. This study aimed to screen the food label of products that are sold in Jordanian market in terms of serving size, energy, macronutrient, fiber, total and added sugars, saturated and trans fat, cholesterol, dietary fiber, and micronutrient contents. A cross-sectional study was performed to screen the food label for the food products based on the standards of The United States Food and Drug Administration (FDA) regulations of 2016 and Jordan Food and Drug Administration (JFDA). Generally, food labels were not clear. The screened products were compliant with JFDA standards and not in compliance with some FDA standards. In addition, many products were found to be sources of added sugars, Na, and saturated fats. Stakeholders and legislators are called to focus on developing new laws, regulations, and polices for developing food label. Food manufacturers are needed to work hardly on developing informative, clear, easy-to-understand, and attractive food labels. The legislators of food label policies are called to look for ways to indicate the presence of high amounts of dietary risk factors such as sugars, added sugars, Na, saturated, and trans fats in packaged foods.

Effective Communication Between Medical Writers and Creative Teams: The Secret Condiment for a Flavorsome Sauce

An impactful pharmaceutical promotional piece is an amalgam of a relatable narrative and agreeable visuals, a result of a highly synergistic relationship among medical writers, art directors, and designers. When it comes to innovation and creativity, a collaborative relationship will increase the likelihood of producing a piece that will touch the lives of the audience in a memorable way. Although the audience of pharmaceutical promotion can comprise health care providers and patients, this article will focus on the latter. A few aspects of this partnership have been shown to increase the chances of achieving that goal, such as respectful communication, alignment on the brief, mutual encouragement, and use of lay language during discussions and brainstorming sessions. Although nurturing storytelling, a strong skill of creative teams, is critical for the success of promotional medical pieces, ensuring scientific accuracy and avoiding misbranding are also key for complying with the ethical paradigms of medical communication and the US Food and Drug Administration regulations. Therefore, fine-tuning the partnership between medical and creative teams translates into a collaboration that combines freedom of creation with regulatory and scientific guardrails, as well as a strong sense of respect for each other’s views and expertise.

Disease Burden Affects Outcomes in Pediatric and Young Adult B-Cell Lymphoblastic Leukemia After Commercial Tisagenlecleucel: A Pediatric Real-World Chimeric Antigen Receptor Consortium Report.

Tisagenlecleucel is a CD19-specific chimeric antigen receptor T-cell therapy, US Food and Drug Administration-approved for children, adolescents, and young adults (CAYA) with relapsed and/or refractory (RR) B-cell acute lymphoblastic leukemia (B-ALL). The US Food and Drug Administration registration for tisagenlecleucel was based on a complete response (CR) rate of 81%, 12-month overall survival (OS) of 76%, and event-free survival (EFS) of 50%. We report clinical outcomes and analyze covariates of outcomes after commercial tisagenlecleucel. We conducted a retrospective, multi-institutional study of CAYA with RR B-ALL across 15 US institutions, who underwent leukapheresis shipment to Novartis for commercial tisagenlecleucel. A total of 200 patients were included in an intent-to-treat response analysis, and 185 infused patients were analyzed for survival and toxicity. Intent-to-treat analysis demonstrates a 79% morphologic CR rate (95% CI, 72 to 84). The infused cohort had an 85% CR (95% CI, 79 to 89) and 12-month OS of 72% and EFS of 50%, with 335 days of median follow-up. Notably, 48% of patients had low-disease burden (< 5% bone marrow lymphoblasts, no CNS3, or other extramedullary disease), or undetectable disease, pretisagenlecleucel. Univariate and multivariate analyses associate high-disease burden (HB, ≥ 5% bone marrow lymphoblasts, CNS3, or non-CNS extramedullary) with inferior outcomes, with a 12-month OS of 58% and EFS of 31% compared with low-disease burden (OS; 85%, EFS; 70%) and undetectable disease (OS; 95%, EFS; 72%; P < .0001 for OS and EFS). Grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 21% and 7% overall and 35% and 9% in patients with HB, respectively. Commercial tisagenlecleucel in CAYA RR B-ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies HB preinfusion to associate with inferior OS and EFS and increased toxicity.

Knowledge Management Approach in Law Enforcement Division of Indonesian Food and Drug Authority to Improve Organizational Performance

Indonesian Food and Drug Authority (BPOM) functions are to conduct investigations into violations of Food and Drug Administration regulation. It protects the public from the illegal distribution of drugs, traditional medicines, dietary supplements, cosmetics, and foods that could harm health. However, in practice, the implementation of law enforcement has not been optimal due to several factors, including the lack of a system or database that allows for the sharing of knowledge, experience, and lessons learned that can aid in decision making regarding the law enforcement process. This research aims to assess the current system of knowledge management and find the knowledge management strategies that support the organization's performance. The findings show that the BPOM Law Enforcement Division currently lacks knowledge management. It shows that there is a lack of skill in converting tacit knowledge into explicit knowledge. The system does not support facilitation. Recommendations are made for the BPOM Law Enforcement Division to establish a standardized documentation and database system and build facilities, infrastructure, and information systems supported by the leader and system. This study can help all work units, particularly the Law Enforcement Division, improve quality and maximize available human resources.

Washington Committee for Neurological Surgery: the evolution of neurosurgery's involvement in public policy.

The American Association of Neurological Surgeons/Congress of Neurological Surgeons Washington Committee was formed in 1975 to establish a means for neurosurgery to influence federal health care policy. In response to growing federal health care legislation and regulation, the Washington Committee expanded from its original six members in 1975 to 35 invited liaisons and members by 2020. The Washington Committee, through the Washington Office, expanded political lobbying capacity into numerous important areas of health care policy, including Current Procedural Terminology coding and Medicare reimbursement, Federal Drug Administration (FDA) regulation, healthcare quality oversight, emergency medical services, treatment guidelines, treatment outcome registries, medical liability reform, research funding, and information dissemination. Over 45 yr, the Washington Committee has become an indispensable resource for shaping public policy affecting neurosurgery training, research, and practice.