Food And Drug Administration Clearance Research Articles

FDA-cleared home sleep apnea testing devices

The demand for home sleep apnea testing (HSAT) devices is escalating, particularly in the context of the coronavirus 2019 (COVID-19) pandemic. The absence of standardized development and verification procedures poses a significant challenge. This study meticulously analyzed the approval process characteristics of HSAT devices by the U.S. Food and Drug Administration (FDA) from September 1, 2003, to September 1, 2023, with a primary focus on ensuring safety and clinical effectiveness. We examined 58 reports out of 1046 that underwent FDA clearance via the 510(k) and de novo pathways. A substantial surge in certifications after the 2022 pandemic was observed. Type-3 devices dominated, signifying a growing trend for both home and clinical use. Key measurement items included respiration and sleep analysis, with the apnea–hypopnea index (AHI) and sleep stage emerging as pivotal indicators. The majority of FDA-cleared HSAT devices adhered to electrical safety and biocompatibility standards. Critical considerations encompass performance and function testing, usability, and cybersecurity. This study emphasized the nearly indispensable role of clinical trials in ensuring the clinical effectiveness of HSAT devices. Future studies should propose guidances that specify stringent requirements, robust clinical trial designs, and comprehensive performance criteria to guarantee the minimum safety and clinical effectiveness of HSATs.

Postmarket Surveillance for Effective Regulation of Digital Mental Health Treatments.

Postmarket Surveillance for Effective Regulation of Digital Mental Health Treatments.

Ligelizumab: A novel molecule in the management of chronic spontaneous urticaria

The next-generation high affinity monoclonal immunoglobulin E (IgE) inhibitor Ligelizumab is being tested in clinical studies to treat chronic spontaneous urticaria (CSU). In 2020, the US Food and Drug Administration (FDA) designated Ligelizumab (QGE031) as a breakthrough therapy for patients with chronic idiopathic urticaria; however, FDA clearance has not yet been granted, despite the phase 3 trial’s completion. Recent clinical investigations have shown that it has a considerable affinity for the high-affinity IgE receptor (FcRI) on the surface of immune cells, which is quite beneficial in the management of the distressing symptoms of CSU. Studies have been done comparing Ligelizumab to Omalizumab, the current standard of care for treating CSU that is refractory. While omalizumab is more effective than Ligelizumab at inhibiting IgE: CD23 interactions, Ligelizumab exhibits stronger inhibition of IgE binding to FcRI, basophil activation, IgE synthesis by B cells, and passive systemic anaphylaxis. To learn about this molecule’s extended characteristics, long-term efficacy and safety, and potential uses in other dermatological disorders, more clinical data is needed.

An Apple a Day to Keep the Parkinson's Disease Doctor Away?

It is challenging to reliably assess the motor features of Parkinson's disease in real-time. This has motivated the search for new digital outcomes that can objectively and remotely measure the severity of parkinsonian motor impairments over an extended period of time. The United States Food and Drug Administration (FDA) has recently granted a 510(k) clearance to the Rune Labs Kinematics System, an ambulatory, smartwatch-based monitoring system to remotely track tremor and dyskinesias in persons with Parkinson's disease. The FDA clearance means that this new digital approach can be regarded as being safe for use in daily practice, with acceptable correlations to clinically based measures. However, the immediate implications for clinicians are limited, because it remains to be demonstrated whether the digital signals correlate well to clinically meaningful outcomes at patient level. The impact on research is also restricted for now, as more validation studies are needed before this new digital approach can be used as primary or secondary endpoint in clinical trials. ANN NEUROL 2023;93:681-685.

Evaluation of Piperacillin-Tazobactam Testing against Enterobacterales by the Phoenix, MicroScan, and Vitek2 Tests Using Updated Clinical and Laboratory Standards Institute Breakpoints.

In 2022, the Clinical and Laboratory Standards Institute (CLSI) updated piperacillin-tazobactam (TZP) breakpoints for Enterobacterales, based on substantial data suggesting that historical breakpoints did not predict treatment outcomes for TZP. The U.S. Food and Drug Administration (FDA) has not yet adopted these breakpoints, meaning commercial manufacturers of antimicrobial susceptibility testing devices cannot obtain FDA clearance for the revised breakpoints. We evaluated the Phoenix (BD, Sparks, MD), MicroScan (Beckman Coulter, Sacramento, CA), and Vitek2 (bioMérieux, Durham, NC) TZP MICs compared to reference broth microdilution for a collection of 284 Enterobacterales isolates. Phoenix (n = 167 isolates) demonstrated 84.4% categorical agreement (CA), with 4.2% very major errors (VMEs) and 1.8% major errors (MEs) by CLSI breakpoints. In contrast, CA was 85.0% with 4.3% VMEs and 0.8% MEs for the Phoenix with FDA breakpoints. MicroScan (n = 55 isolates) demonstrated 80.0% CA, 36.4% VMEs, and 4.8% MEs by CLSI breakpoints and 81.8% CA, 44.4% VMEs, and 0.0% MEs by FDA breakpoints. Vitek2 (n = 62 isolates) demonstrated 95.2% CA, 6.3% VMEs, and 0.0% MEs by CLSI and 96.8% CA, 0.0% VMEs, and 2.2% MEs by FDA breakpoints. Overall, the performance of the test systems was not substantially different using CLSI breakpoints off-label than using on-label FDA breakpoints. However, limitations were noted with higher-than-desired VME rates (all three systems) and lower-than-desired CA (MicroScan and Phoenix). Laboratories should consider adoption of the revised CLSI breakpoints with automated test systems but be aware that some performance challenges exist for testing TZP on automated systems, regardless of breakpoints applied.

Accelerating Human Immunodeficiency Virus Self-Testing in the United States: A Call to Action.

Human immunodeficiency virus (HIV) self-testing has emerged as a tool to increase the proportion of people to know their status. Since the first HIV self-test was approved in 2012 by the US Food and Drug Administration (FDA), global access to HIV self-tests has been bolstered by public-private partnerships to ensure equitable access in low- and middle-income countries. However, no company has applied for FDA clearance in a decade. We highlight the potential benefits to reclassifying HIV self-tests from class III to class II.

Evaluation of Over-the-Counter Portable Oxygen Concentrators Utilizing a Metabolic Simulator.

Supplemental oxygen is designed to raise alveolar PO2 to facilitate diffusion into arterial blood. Oxygen is generally delivered by nasal cannula either by continuous or pulsatile flow. Battery-powered portable oxygen concentrators (POCs) facilitate ambulation in patients experiencing exertional hypoxemia. In the United States, the Food and Drug Administration (FDA) clears these devices to be sold by physician prescription. Recently, however, lower-cost devices described as POCs have been advertised by online retailers. These devices lack FDA clearance and are obtained over the counter (OTC) without prescription. This study determined whether a selected group of OTC POCs have oxygen delivery characteristics suitable for use by hypoxemic patients. A metabolic simulator, capable of simulating a range of metabolic rates and minute ventilations, determined effects of oxygen supplementation delivered by a variety of devices on alveolar PO2 . Devices tested included 3 OTC POCs, an FDA-cleared POC, and continuous-flow oxygen from a compressed oxygen cylinder. End-tidal PETO2 , a surrogate of alveolar PO2 , was determined at each of each device's flow settings at 3 metabolic rates. Continuous-flow tank oxygen yielded a linear PETO2 increase as flow increased, with progressively lower slope of increase for higher metabolic rate. The prescription POC device yielded similar PETO2 elevations, though with somewhat smaller elevations in pulse-dose operation. One OTC POC was only technically portable (no on-board battery); it provided only modest PETO2 elevation that failed to increase as flow setting was incremented. A second OTC POC produced only minimal PETO2 elevation. A third OTC POC, a pulsed-dose device, produced meaningful PETO2 increases, though not as great as the prescription device. Only one of 3 OTC POCs tested was potentially of use by patients requiring ambulatory oxygen. Physicians and respiratory therapists should inform patients requiring portable oxygen that OTC devices may not meet their oxygenation requirements.

Trends in clinical validation and usage of US Food and Drug Administration-cleared artificial intelligence algorithms for medical imaging

To examine the current landscape of US Food and Drug Administration (FDA)-approved artificial intelligence (AI) medical imaging devices and identify trends in clinical validation strategy. A retrospective study was conducted that analysed data extracted from the American College of Radiology (ACR) Data Science Institute AI Central database as of November 2021 to identify trends in FDA clearance of AI products related to medical imaging. Product and clinical validation information of each device was gathered from their respective public 510(k) summary or de novo request submission, depending on their type of authorisation. Overall, the database included a total of 151 AI algorithms that were cleared by the FDA between 2008 and November 2021. Out of the 151 FDA summaries reviewed, 97 (64.2%) reported the use of clinical data to validate their device, with six (4%) revealing study participant demographics, and eight (5.3%) reporting the specifications of the machines used. A total of 51 (33.8%) AI devices characterised their clinical data as multicentre, three (2%) as single-centre, and the remaining 97 (64.2%) did not specify. The ground truth used for clinical validation was specified in 78 (51.6%) FDA summaries. A wide breadth of AI algorithms has been developed for medical imaging. Most of the FDA summaries of the devices mention their use of clinical data and patient cases for device validation; however, few devices revealed the patient demographics or machine specifications used in their clinical studies, which may lead some consumers to question their external validation.

Orbital Implants Receiving Food and Drug Administration Premarket Notification.

This perspective explores the Food and Drug Administration (FDA) 510(k) program, occasionally referred to as premarket notification, which facilitates faster marketing of Class II medical devices, such as orbital implants by demonstrating "substantial equivalence" to previously approved devices. This allows for FDA clearance, rather than FDA approval of orbital implants via comparison to currently marketed implants rather than clinically proven safety standards. Utilizing the FDA's publicly available 510(k) Premarket Notification database, we conducted a thorough search of FDA-cleared orbital implants dating back to the inception of the 510(k) process in 1976. We found that 29 orbital implants received 510(k) FDA clearance between 1987 and 2022. Four of the 29 implants were recalled. Only 9 of 29 implants had available data on their predicate or comparison devices; of these 9, 3 implants received clearance based on devices that were subsequently recalled. This investigation into premarket approval of orbital implants identifies a shortcoming in the FDA 510(k) approval process. Long-term implant-associated morbidity is difficult to predict during premarket analysis but is further complicated for 510(k) cleared implants since devices approved based on substantial equivalence to recalled devices may not be automatically recalled. Clinicians should be aware of the approval process for the devices they select, and review of the 510(k) process, especially as it applies to substantial equivalence to devices subsequently recalled is warranted.

First Food and Drug Administration Cleared Thin-Film Electrode for Intracranial Stimulation, Recording, and Monitoring of Brain Activity-Part 1: Biocompatibility Testing.

Subdural strip and grid invasive electroencephalography electrodes are routinely used for surgical evaluation of patients with drug-resistant epilepsy (DRE). Although these electrodes have been in the United States market for decades (first FDA clearance 1985), their fabrication, materials, and properties have hardly changed. Existing commercially available electrodes are made of silicone, are thick (>0.5 mm), and do not optimally conform to brain convolutions. New thin-film polyimide electrodes (0.08 mm) have been manufactured to address these issues. While different thin-film electrodes are available for research use, to date, only one electrode is cleared by Food and Drug Administration (FDA) for use in clinical practice. This study describes the biocompatibility tests that led to this clearance. Biocompatibility was tested using standard methods according to International Organization for Standardization (ISO) 10993. Electrodes and appropriate control materials were bent, folded, and placed in the appropriate extraction vehicles, or implanted. The extracts were used for in vitro and in vivo tests, to assess the effects of any potential extractable and leachable materials that may be toxic to the body. In vitro studies included cytotoxicity tested in L929 cell line, genotoxicity tested using mouse lymphoma assay (MLA) and Ames assay, and hemolysis tested in rabbit whole blood samples. The results indicated that the electrodes were non-cytotoxic, non-mutagenic, non-clastogenic, and non-hemolytic. In vivo studies included sensitization tested in guinea pigs, irritation tested in rabbits, acute systemic toxicity testing in mice, pyrogenicity tested in rabbits, and a prolonged 28-day subdural implant in sheep. The results indicated that the electrodes induced no sensitization and irritation, no weight loss, and no temperature increase. Histological examination of the sheep brain tissue showed no or minimal immune cell accumulation, necrosis, neovascularization, fibrosis, and astrocyte infiltration, with no differences from the control material. In summary, biocompatibility studies indicated that these new thin-film electrodes are appropriate for human use. As a result, the electrodes were cleared by the FDA for use in clinical practice [510(k) K192764], making it the first thin-film subdural electrode to progress from research to clinic. Its readiness as a commercial product ensures availability to all patients undergoing surgical evaluation for DRE.

FDA-regulated AI Algorithms: Trends, Strengths, and Gaps of Validation Studies

To assess key trends, strengths, and gaps in validation studies of the Food and Drug Administration (FDA)-regulated imaging-based artificial intelligence/machine learning (AI/ML) algorithms. We audited publicly available details of regulated AI/ML algorithms in imaging from 2008 until April 2021. We reviewed 127 regulated software (118 AI/ML) to classify information related to their parent company, subspecialty, body area and specific anatomy type, imaging modality, date of FDA clearance, indications for use, target pathology (such as trauma) and findings (such as fracture), technique (CAD triage, CAD detection and/or characterization, CAD acquisition or improvement, and image processing/quantification), product performance, presence, type, strength and availability of clinical validation data. Pertaining to validation data, where available, we recorded the number of patients or studies included, sensitivity, specificity, accuracy, and/or receiver operating characteristic area under the curve, along with information on ground-truthing of use-cases. Data were analyzed with pivot tables and charts for descriptive statistics and trends. We noted an increasing number of FDA-regulated AI/ML from 2008 to 2021. Seventeen (17/118) regulated AI/ML algorithms posted no validation claims or data. Just 9/118 reviewed AI/ML algorithms had a validation dataset sizes of over 1000 patients. The most common type of AI/ML included image processing/quantification (IPQ; n=59/118), and triage (CADt; n=27/118). Brain, breast, and lungs dominated the targeted body regions of interest. Insufficient public information on validation datasets in several FDA-regulated AI/ML algorithms makes it difficult to justify clinical applications since their generalizability and presence of bias cannot be inferred.

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

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

Freudenberg surgical masks receive FDA clearance

ASTM Level 3 surgical masks manufactured by Freudenberg Performance Materials have secured 510(k) clearance from the US Food and Drug Administration (FDA).

First clinical implementation of GammaTile permanent brain implants after FDA clearance

PurposeGammaTile cesium-131 (131Cs) permanent brain implant has received Food and Drug Administration (FDA) clearance as a promising treatment for certain brain tumors. Our center was the first institution in the United States after FDA clearance to offer the clinical use of GammaTile brachytherapy outside of a clinical trial. The purpose of this work is to aid the medical physicist and radiation oncologist in implementing this collagen carrier tile brachytherapy (CTBT) program in their practice. MethodsA total of 23 patients have been treated with GammaTile to date at our center. Treatment planning system (TPS) commissioning was performed by configuring the parameters for the 131Cs (IsoRay Model CS-1, Rev2) source, and doses were validated with the consensus data from the American Association of Physicists in Medicine TG-43U1S2. Implant procedures, dosimetry, postimplant planning, and target delineations were established based on our clinical experience. Radiation safety aspects were evaluated based on exposure rate measurements of implanted patients, as well as body and ring badge measurements. ResultsAn estimated timeframe of the GammaTile clinical responsibilities for the medical physicist, radiation oncologist, and neurosurgeon is presented. TPS doses were validated with published dose to water for 131Cs. Clinical aspects, including estimation of the number of tiles, treatment planning, dosimetry, and radiation safety considerations, are presented. ConclusionThe implementation of the GammaTile program requires collaboration from multiple specialties, including medical physics, radiation oncology, and neurosurgery. This manuscript provides a roadmap for the implementation of this therapy.

Profile of Somryst Prescription Digital Therapeutic for Chronic Insomnia: Overview of Safety and Efficacy

ABSTRACT Introduction: Prescription digital therapeutics (PDTs) represent a new class of software-based medical devices authorized by the Food and Drug Administration (FDA) to treat disease. Somryst™, the first PDT for treating chronic insomnia, delivers cognitive behavioral therapy for insomnia (CBT-I) via a mobile application. CBT-I is the guideline-recommended, first-line treatment for chronic insomnia, but availability of CBT-I therapists is limited. Somryst addresses this need by providing asynchronous access to CBT-I treatment. As a contactless therapeutic medium, Somryst is also an ideal option when face-to-face therapy is not available or recommended for safety reasons (e.g. because of possible exposure to the SARS-CoV-2 virus). Areas covered: This review summarizes the mechanisms of action and technical features of Somryst, and describes safety and effectiveness data from the randomized trials on which FDA clearance was based. Expert opinion: Somryst demonstrates robust clinical efficacy with a favorable benefit-to-risk profile for treating adults with chronic insomnia. FDA clearance was based on data from 2 clinical trials of the first-generation web-based CBT-I platform Sleep Healthy Using the Internet (SHUTi). Somryst, and PDTs in general, are promising devices to address the need for greater accessibility to effective therapies.

Home-Based Testing for Sexually Transmitted Infections: Leveraging Online Resources During the COVID-19 Pandemic.

Home-Based Testing for Sexually Transmitted Infections: Leveraging Online Resources During the COVID-19 Pandemic.

Wearables for arrhythmia care: Challenges and future prospects

Wearables for arrhythmia care: Challenges and future prospects

FDA OKs ADHD Video Game Therapy

FDA OKs ADHD Video Game Therapy

Endoscopic transmission of carbapenem-resistant Enterobacteriaceae: implications for U.S. Food and Drug Administration approval and postmarket surveillance of endoscopic devices

Since the first widely reported case cluster of duodenoscope-associated transmission of carbapenem-resistant Enterobacteriaceae (CRE) in 2013 that affected 38 patients, similar outbreaks have occurred throughout the world. The U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention, professional gastroenterology societies, and endoscope manufacturers have taken multiple steps to address this issue. Unlike prior outbreaks attributed to lapses in cleaning and reprocessing, transmission and outbreaks have continued to occur despite compliance with current reprocessing guidelines. A definitive method of duodenoscope reprocessing remains elusive, and the FDA recently recommended transition to new designs with disposable components that do not require reprocessing. The first fully disposable duodenoscope received FDA clearance as a "breakthrough" device in December 2019. Although the human, microbiologic, and endoscopic design factors responsible for infectious transmissions and disinfecting techniques to avoid them have been examined, discussion has not included the critical role of FDA regulation of duodenoscopes through the 510(k) clearance pathway and the mechanisms of postmarket surveillance, including adverse event reporting. We present an overview of the FDA approval of duodenoscopes by analyzing the FDA's 510(k) premarket notification database for data supporting clearance of duodenoscope models implicated in CRE-related outbreaks as well as subsequently required postmarket studies. We address the policy implications of CRE outbreaks on postmarketing surveillance and the need for increased gastroenterologist involvement in the life cycle of duodenoscopes and other medical devices. This includes reporting thorough adverse event data to the FDA and device manufacturers, supporting active surveillance studies to ensuresafety and effectiveness, and evaluating implementation of recommendations to reduce adverse events.

Simultaneous Evaluation of Diagnostic Assays for Pharyngeal and Rectal Neisseria gonorrhoeae and Chlamydia trachomatis Using a Master Protocol.

BackgroundPharyngeal and rectal Neisseria gonorrhoeae and Chlamydia trachomatis play important roles in infection and antibacterial resistance transmission, but no US Food and Drug Administration (FDA)–cleared assays for detection at these sites existed prior to this study. The objective was to estimate performance of assays to detect those infections in pharyngeal and rectal specimens to support regulatory submission.MethodsWe performed a cross-sectional, single-visit study of adults seeking sexually transmitted infection testing at 9 clinics in 7 states. We collected pharyngeal and rectal swabs from participants. The primary outcome was positive and negative percent agreement for detection of N. gonorrhoeae and C. trachomatis for 3 investigational assays compared to a composite reference. Secondary outcomes included positivity as well as positive and negative predictive values and likelihood ratios. Subgroup analyses included outcomes by symptom status and sex.ResultsA total of 2598 participants (79% male) underwent testing. We observed N. gonorrhoeae positivity of 8.1% in the pharynx and 7.9% in the rectum and C. trachomatis positivity of 2.0% in the pharynx and 8.7% in the rectum. Positive percent agreement ranged from 84.8% to 96.5% for different anatomic site infection combinations, whereas negative percent agreement was 98.8% to 99.6%.ConclusionsThis study utilized a Master Protocol to generate diagnostic performance data for multiple assays from different manufacturers in a single study population, which ultimately supported first-in-class FDA clearance for extragenital assays. We observed very good positive percent agreement when compared to a composite reference method for the detection of both pharyngeal and rectal N. gonorrhoeae and C. trachomatis.Clinical Trials RegistrationNCT02870101.