Premarket Approval Research Articles

Preliminary Review of Relationship between Medical Device Evaluation and Quality Management System in Premarket Approval

This paper analyzed the current reform of review and approval mechanism for medical devices and discussed the method for technical review process extending to product quality controllable direction and found the measures and suggestions to strengthen technical review for quality management system with the help with complementary relationship between the technical review and the quality management system assessment of the pre-market registration. Nowadays, because of the demand of eRPS， MAH and the amendment of regulation, the integration of technical review and quality management system is more important, necessary and scientific. Scientific and systematic evaluation should be carried out to strengthen the pre-market approval of medical devices and ensure the safety and effectiveness of medical products.

Cultivating Evidence‐Based Pathways for Cannabis Product Development: Implications for Consumer Protection†

Disparities between federal and state cannabis regulation, coupled with protracted federal enforcement, have facilitated the proliferation of a multi–billion dollar cannabis industry that generally evades compliance with federal consumer protection laws. The Federal Food, Drug and Cosmetic Act (FDCA) established regulatory pathways for the lawful development of products such as food, drugs, and dietary supplements. The FDCA uses a science‐based approach to protect consumers from harmful products, but early inconsistencies between state and federal cannabis regulation prevented and/or discouraged the cannabis industry from complying with FDCA requirements. Cannabis products are promoted as safe and attributed with providing effective therapeutic treatment for numerous medical conditions, yet the claims often lack the rigorous evidence‐based support typically expected by regulators and the medical community. The Food and Drug Administration (FDA) has announced its expectation that cannabidiol (CBD) products comply with the FDCA and follow a science‐based approach to product development. The FDA is addressing violations involving unsubstantiated CBD health claims and is working to clarify the future regulatory pathway for CBD products. Meanwhile, the state‐approved cannabis market continues to operate, selling numerous products that have circumvented the FDCA consumer protections. This article examines the need for strengthening consumer protections in the cannabis market. We use evidence‐based medicine as a model to address the importance of science‐based product development and to contextualize a science‐based comparison of regulatory pathways for cannabis drugs, food, and dietary supplements.

Responses to Liability Immunization: Evidence from Medical Devices

The Supreme Court's decision in Riegel v. Medtronic immunized medical device manufacturers from certain types of state product liability claims. However, this immunization applies only when the devices underlying those claims have been approved through the Food and Drug Administration's most rigorous—and costly—review process, premarket approval (PMA). Exploiting this decision, we examine whether manufacturers strategically respond to this new immunity. We find evidence that, following Riegel, approvals for high‐risk product categories increase relative to the comparable change for low‐risk categories, suggesting that firms are sensitive to the newly immunized risk. We additionally find evidence that physician treatment patterns with respect to medical devices also change, consistent with Riegel shifting liability away from device manufacturers and toward physicians. The analysis provides evidence that sophisticated actors respond to changes in their expected legal liability and that technical legal decisions have important ramifications for the provision of healthcare.

Responses to Liability Immunization: Evidence from Medical Devices

The Supreme Court's decision in Riegel v. Medtronic unexpectedly and immediately immunized medical device manufacturers from certain types of state tort liability. Riegel immunized manufacturers from liability if their devices had been approved through the Food and Drug Administration's most rigorous|and costly|review process, premarket approval (PMA). Exploiting this unanticipated decision, we examine whether manufacturers strategically respond to this new immunity. We find evidence that, following the Riegel decision, device manufacturers file more PMA applications for high risk product categories (relative to the comparable change for low risk categories), suggesting that firms are sensitive to the newly immunized risk. We additionally find evidence that physician treatment patterns with respect to medical devices also change, consistent with Riegel shifting liability away from device manufacturers and towards physicians. The analysis provides evidence that sophisticated actors respond to changes in their expected legal liability and that technical legal decisions have important ramifications for the provision of health care.

Research: Evaluation of Orthopedic Hip Device Recalls by the FDA from 2007 to 2017.

Medical device recalls have increased in the previous two decades. Orthopedic devices are estimated to constitute 12% of all medical devices recalled. Medical devices enter the market via the Food and Drug Administration's (FDA's) premarket approval (PMA) or 510(k) pathways. This article evaluates orthopedic hip device recalls between Jan. 1, 2007, and Dec. 31, 2017. We hypothesized that the 510(k) approval process would have substantially higher recall rates for defective devices. The FDA's device recall database was queried for all orthopedic hip devices from Jan. 1, 2007, to Dec. 31, 2017. Each recall included product description, recall number, device class, date of recall posting, date of recall termination, manufacturer, FDA-determined cause for recall, number of recalled units, distribution, product classification, and method of approval [510(k), PMA, or unspecified]. In total, 774 orthopedic hip devices were recalled between Jan. 1, 2007, and Dec. 31, 2017. The 510(k) approval process constituted 85% of hip device recalls. The most common FDA-determined cause of hip device recalls was device design, which constituted 37% of 510(k)-approved device recalls but only 6% of PMA-approved device recalls. The most recalled hip devices were hip prostheses. Orthopedic hip device recalls have shown a decrease of about 10 recalls per year during the 11-year period of analysis. Devices approved through the 510(k) process, compared with the PMA process, were more likely to be recalled for design defects. Although device design is the most common reason for device recall, many recalls are due to suboptimally standardized processes (e.g., packaging, process controls, device labeling). Overall, orthopedic hip device recalls decreased during the period of analysis (2007-17).

Translating Observational Research into Regulatory Science: The Role of U.S. EPA's Office of Pesticide Programs in Evaluating Epidemiologic Evidence

The U.S. Environmental Protection Agency’s Office of Pesticide Programs (OPP) is a licensing program that regulates pesticides in the U.S under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). As part of this program, OPP has a regulatory mandate to evaluate a substantial body of health effect and exposure data in order to assess the effects of pesticides on human health. Through this evaluation, OPP plays a critical role in translating observational research into regulatory science and aims to ensure that pesticide risk assessments incorporate epidemiologic evidence on the potential adverse effects on people that may result from pesticide exposure through dietary, environmental, and occupational exposure pathways. The thematic poster will provide background on OPP’s regulatory requirements and then describe the systematic review methodology used to evaluate epidemiologic evidence based on a scientifically robust and transparent approach. This description will emphasize key regulatory considerations and outline elements of OPP’s 2016 framework for incorporating epidemiological data into risk assessments for pesticides. The 2016 framework may be of interest to a range of stakeholders in the scientific community and characterizes OPP’s “fit-for-purpose” approach to systematic review. OPP uses this approach to define to the scope and complexity of reviews and integrate epidemiologic findings into OPP’s overall risk assessment process.

Dissemination of CATCH My Breath, a middle school E-Cigarette prevention program

ObjectivesIn 2016, the US Surgeon General issued a Call to Action to address adolescent e-cigarette use and school-based prevention interventions are an effective component of comprehensive tobacco control. This study describes the development and dissemination of CATCH My Breath, an e-cigarette prevention program for middle and high school students. MethodsStarting in 2014, a university and nonprofit collaboration designed, formatively evaluated, pilot tested, and disseminated the CATCH My Breath Program (CMB). The team used Social Cognitive Theory to develop the program and Diffusion of Innovations Theory to disseminate the program. Dissemination strategies were applied beginning in 2016. This paper describes the application of both theories and the resulting reach of CMB. ResultsSince dissemination began, CMB has been rapidly adopted, following the typical diffusion normal curve. As of June 2020, approximately 4,000 schools in the United States have adopted the program, 70,000 teachers have taught the program, and 1,400,000 students have been exposed to program materials. ConclusionThe application of Social Cognitive Theory and Diffusion of Innovation Theory resulted in effective prevention results and rapid, widespread adoption of the CMB. This level of adoption and implementation represents 25% of the school marketplace. CMB should be considered as the school component of the recommended combustible and e-cigarette prevention and control toolkit, alongside mass media, marketing restrictions, retail access, taxation, flavor ban, and FDA premarket approval. Other public health interventions seeking rapid adoption should consider applying principles of Diffusion of Innovation as a guide for development and dissemination.

Weak and fragmented regulatory frameworks on the accuracy of blood pressure-measuring devices pose a major impediment for the implementation of HEARTS in the Americas.

Global HEARTS is a WHO initiative for cardiovascular disease prevention and control. Accurate blood pressure (BP) measurement is an essential component of the initiative. This study aimed to determine the regulatory frameworks governing the accuracy of BPMDs in countries of the Americas participating in the HEARTS initiative. Quantitative and qualitative analysis of the laws and regulations relevant to ensuring the accuracy of BPMDs were determined from the Ministries of Health/Regulatory Agencies among 13 countries in Latin America and the Caribbean. Analysis included characterizing the scope of regulations (ie, pre-market approval, sales and promotion, labeling, cuff sizes, and procurement), information systems for monitoring the models of BPMDs used in primary health care (PHC), and systems to enforce compliance with regulations. Ten of the 13 countries had medical device laws, but regulations that specifically address BPMDs only existed in three countries. Only one country (Brazil) had regulations for mandatory accuracy validation testing and only two countries regulated internet sales of BPMDs. Labeling and cuff size regulations existed in four and two countries, respectively. Less than half the countries reported having a data repository on the BPMD models being used in PHC facilities (four countries) or sold (five countries). Weak and fragmented regulatory frameworks on the accuracy of BPMDs exist among countries of the Americas. This will adversely affect the accuracy of blood pressure assessment and hence poses a major impediment for successful implementation of HEARTS initiative.

The state of artificial intelligence-based FDA-approved medical devices and algorithms: an online database

At the beginning of the artificial intelligence (AI)/machine learning (ML) era, the expectations are high, and experts foresee that AI/ML shows potential for diagnosing, managing and treating a wide variety of medical conditions. However, the obstacles for implementation of AI/ML in daily clinical practice are numerous, especially regarding the regulation of these technologies. Therefore, we provide an insight into the currently available AI/ML-based medical devices and algorithms that have been approved by the US Food & Drugs Administration (FDA). We aimed to raise awareness of the importance of regulatory bodies, clearly stating whether a medical device is AI/ML based or not. Cross-checking and validating all approvals, we identified 64 AI/ML based, FDA approved medical devices and algorithms. Out of those, only 29 (45%) mentioned any AI/ML-related expressions in the official FDA announcement. The majority (85.9%) was approved by the FDA with a 510(k) clearance, while 8 (12.5%) received de novo pathway clearance and one (1.6%) premarket approval (PMA) clearance. Most of these technologies, notably 30 (46.9%), 16 (25.0%), and 10 (15.6%) were developed for the fields of Radiology, Cardiology and Internal Medicine/General Practice respectively. We have launched the first comprehensive and open access database of strictly AI/ML-based medical technologies that have been approved by the FDA. The database will be constantly updated.

Postmarket Clinical Evidence for High-Risk Therapeutic Medical Devices Receiving Food and Drug Administration Premarket Approval in 2010 and 2011

This cross-sectional study provides a 5-year update on the status and availability of postmarket evidence for high-risk medical devices that received FDA premarket approval in 2010 and 2011.

Recall Rates of Total Knee Arthroplasty Devices Are Dependent on the FDA Approval Process.

IntroductionThe medical device industry has grown substantially in recent years. There is limited research examining orthopedic subspecialties and the recall of orthopedic devices. We hypothesize that knee arthroplasty devices cleared through the Food and Drug Administration (FDA) 510(k)-notification process would have a higher recall rate than the premarket approval (PMA) process.MethodsThe FDA database was thoroughly queried for all knee arthroplasty surgical devices from January 1, 2007 through December 31, 2017. Recalled devices were analyzed by manufacturer, type of implant, recall class, manufacturer-determined reason, FDA-determined reason, quantity affected, submission type, and distribution within the United States or internationally.ResultsOut of over 30,000 medical devices on the market, a total of 300 knee arthroplasty devices from 18 different companies were recalled during the time frame of this study. Tibial components accounted for 35.33% of devices, polyethylene implants for 38.67%, and femoral components for 15%. The most common reason for recall was device design (n = 134, 44.67%), followed by process control (n = 32, 10.67%). Of the 300 knee arthroplasty devices recalled, 267 (89.0%) were cleared through the 510(k) premarket notification process and 33 (11.0%) devices were approved through the PMA process.ConclusionsA larger proportion of knee arthroplasty surgical devices cleared through the 510(k) process were recalled compared to implants approved through the stricter PMA process. Changing the 510(k) process may enable manufacturers to improve upon the safety of their devices.

To CBD or not to CBD?: What pharmacists need to know

To CBD or not to CBD?: What pharmacists need to know

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.

Establishment of a Serological Panel for In Vitro Diagnostics of Severe Acute Respiratory Syndrome

Severe acute respiratory syndrome (SARS) is an infectious disease with a high mortality rate. Because SARS suddenly disappeared after an approximately 1-year-long pandemic period (November 2002 to July 2003), insufficient data was available for the development of in vitro diagnostics for SARS (SARS IVD). To rapidly identify cases in the event of future epidemics, it is necessary to establish a SARS serological panel. In this study, 20 SARS convalescent sera and 20 normal sera from the Taiwan CDC were used to establish a SARS serological panel. This can be used as a standard for the Taiwan FDA to evaluate the effectiveness of SARS IVDs during the premarket approval process. To characterize the immunological activity, protein extracts containing SARS coronavirus (SARS-CoV) proteins, synthetic viral peptide fragments and recombinant viral proteins, were used to detect antibody reactivity. Results demonstrated that synthetic S, M, N peptide fragments and whole SARS-CoV protein extracts had stronger antigenicity than individual recombinant viral proteins. Moreover, results of the ELISA and the immunofluorescence assay indicated that our SARS panel had no cross-reactivity with the human coronavirus 229E, and displayed weak cross-reactivity with human coronavirus OC43. These findings suggested that our SARS serological panel is suitable for evaluating SARS IVDs.

The Use of a Synthetic Cartilage Implant for Hallux Rigidus: A Systematic Review.

Background. Hallux rigidus is a common pathology afflicting the foot, for which various joint salvage techniques have been described with a multitude of different implants. Recently, a synthetic cartilage implant composed of polyvinyl alcohol (PVA) received FDA premarket approval for the treatment of arthritis of the great toe. The purpose of this study was to (1) systematically review the clinical evidence supporting the use of a PVA implant in hallux rigidus and (2) determine the strength of the recommendation that can be made supporting the use of a PVA implant by evaluating the quality of evidence available. Methods. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Using the terms "cartiva OR polyvinyl alcohol OR synthetic cartilage OR hemiarthroplasty AND hallux rigidus OR great toe arthritis OR first toe arthritis" we searched the PubMed/Medline database. The quality of the included studies was evaluated using the American Academy of Orthopaedic Surgeons Clinical Practice Guideline and Systematic Review Methodology. Results. Seven studies met the inclusion criteria, 6 of these were derived from a single randomized controlled trial. A moderate recommendation can be given for the use of a PVA implant for hallux rigidus based on short-term outcomes. A limited recommendation can be given for the use of a PVA implant for hallux rigidus based on mid-term outcomes. Conclusion. There are limited studies available detailing the outcomes of a PVA implant for hallux rigidus; however, the results that are available demonstrate a high level of evidence.Levels of Evidence: Level I: Systematic review.

Probiotics: Promise, Evidence, and Hope

Probiotics: Promise, Evidence, and Hope

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-gene blood-based comprehensive genomic profiling assay.

e13685 Background: As the availability of precision therapies expand, a well-validated blood-based comprehensive genomic profiling (CGP) assay has the potential to provide considerable value as a complement to tissue-based testing to ensure that potentially life-extending therapies are administered to the patients most likely to benefit. Comprehensive clinical and analytical validity data for blood-based assays are crucial to enabling physicians to understand the true performance of available testing options. Methods: The FoundationOne Liquid CDx assay is a blood-based CGP assay that has been validated for a Premarket Approval (PMA) submission to the Food and Drug Administration (FDA). Validation studies included > 9,000 tests and > 30,000 unique variants across > 300 genes and > 50 cancer types, allowing for a comprehensive assessment of performance. Results: The results of these extensive studies demonstrate a 95% limit of detection (LoD) of 0.40% variant allele fraction (VAF) for select short variants (subs and indels), 0.37% VAF for select rearrangements, 21.7% tumor fraction (TF) for select copy number amplifications, and 30.4% TF for copy number losses. LoD for complex biomarkers such as microsatellite instability (MSI) and blood tumor mutational burden (bTMB) were also determined. The limit of blank (LoB) was shown to be the ideal value of zero. Reproducibility of variant calling was determined to be 99.59% with two-sided exact CI of (99.58%, 99.60%). In comparison with an orthogonal method, an overall PPA (95% CI) of 96.3% (94.8, 97.4%) and NPA (95% CI) of > 99.9% (99.9%, 100.0%) was observed. Critically, clinical validity and concordance with tissue-based CGP results across multiple tumor types were also evaluated. Conclusions: The results of these studies demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations (short variants, rearrangements, and copy number alterations), as well as complex biomarkers, such as MSI, bTMB, and tumor fraction. These data demonstrate that the assay can identify genomic variants that may inform therapeutic decisions for cancer patients with any solid tumor using a single blood sample. Additionally, clinical validation results establish FoundationOne Liquid CDx as an additional tool for physicians in the therapeutic management of cancer patients.

Governmental Regulations and Increasing Food and Drug Administration Oversight of Regenerative Medicine Products: What’s New in 2020?

The United States Food and Drug Administration (FDA) is responsible for protecting and promoting public health through rules and regulations. Over the past few years, the field of regenerative medicine and cell therapy have garnered significant interest, and this evolving new biology is changing fast and challenging regulatory bodies. The FDA has published a series of guidance documents outlining steps to protect consumers against potentially dangerous and unproven treatments. The agency has offered a grace period for “stem cell clinics” until November 2020 to come into compliance by obtaining Investigational New Drug applications and working to secure premarket approval of their products. With the documentation of hundreds of “stem cell clinics,” the FDA needs to enforce the adherence to their outlined standards to protect patients. The aim of this review was to provide an overview of these FDA regulations and some current issues within the industry. The purpose is to educate and inform the musculoskeletal community about the current government regulations of this new expanding biology. Level of EvidenceLevel V, expert opinion.

Risk Analysis and Countermeasures Investigating Based on Medical Device Registration Review Process

In order to strengthen the supervision and management of medical devices, China implements pre-market registration and approval system for medical device. Technical evaluation is a key point of Chinese medical device registration management system. This study, by process-oriented, systematically sorts out the risks existing in each part of the review process. The countermeasures for risk prevention are proposed, hoping to strengthen the quality control of the whole process of review, improve the quality and efficiency of the review effectively, and ensure the various reform measures of the medical device review and approval system effectively.

MP30-05 TRENDS IN INNOVATION IN THE SURGICAL MANAGEMENT OF STRESS INCONTINENCE AND PELVIC ORGAN PROLAPSE: A “DEEP DIVE” INTO THE FDA 510(K) AND PREMARKET APPROVAL DATABASES

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I (MP30)1 Apr 2020MP30-05 TRENDS IN INNOVATION IN THE SURGICAL MANAGEMENT OF STRESS INCONTINENCE AND PELVIC ORGAN PROLAPSE: A “DEEP DIVE” INTO THE FDA 510(K) AND PREMARKET APPROVAL DATABASES Cristina Fox* and MD Debra FromerMD Cristina Fox*Cristina Fox* More articles by this author and Debra FromerDebra Fromer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000869.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In 2008, the FDA issued a landmark Public Health Notification (PHN) regarding adverse events of transvaginal mesh (TVM) for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). In 2011, the FDA update stated that serious adverse events of TVM for POP repair are not rare. This same year, an FDA Executive Advisory Panel considered reclassification of TVM for POP repair from Class II (low to moderate risk) to Class III (high risk), which mandated a more extensive and costly Premarket Approval (PMA). The FDA followed with 109 orders for device manufacturers to initiate post-market 522 studies of existing TVM for POP repair and single-incision slings by 2013. In early 2016, up-classification of TVM for POP repair to Class III was announced along with a deadline of mid-2018 for PMAs and 522s. In April 2019 all TVM for POP repair were withdrawn from the market as the FDA revoked their clearance based on 1-year data. This series of events brings to question: how are the FDA regulatory clearance processes affecting trends in surgical innovation in the management of SUI and POP? METHODS: Utilizing the FDA 510(k) and PMA databases on the FDA website, we analyzed the trends of devices granted clearance for POP and SUI between 1999 and 2018. This included both modifications to existing devices and novel devices. Quantification of the number of novel device submissions during this study period was correlated to the FDA issued communications to estimate trends in device innovation. RESULTS: From 1999 to 2018, there were 127 total Cleared 510(k) Premarket Notifications, 48 for POP and 79 for SUI. Of the total submissions, there were 29 novel devices for POP and 40 for SUI. Figure 1 demonstrates a temporal analysis of submissions, correlating to a peak from 2004 to 2008, and accounting for 56% of all submissions. Conversely, post-2008, there is a precipitous drop in novel submissions, resulting in a literal flatline. CONCLUSIONS: The declining trend in device manufacturer innovation correlates with increasing demands from the FDA involving intensive premarket approval processes. Such a trend limits surgical options for women with POP and SUI and threatens the quality, evidence-based care that our patients deserve. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e439-e440 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cristina Fox* More articles by this author Debra Fromer More articles by this author Expand All Advertisement PDF downloadLoading ...