Premarket Submissions Research Articles

Premarket and postmarket regulatory challenges for mechanical ventilators: scenario in Brazil and comparison with other countries

BackgroundThis study critically assesses the regulatory challenges faced in Brazil for mechanical ventilators amid the COVID-19 pandemic. It evaluates the effectiveness of expedited regulatory actions, compares strategies with other countries, and proposes future optimization in emergency conditions. Methods: Premarket submissions of mechanical ventilators were surveyed, involving accompanying certification documentation, rejections, approvals, and cancellations. Postmarket occurrences were surveyed until June 2023, evaluating their incidence and presence of certifications. Regulatory pathways in other countries were reviewed for comparison. Results: Brazil’s regulatory strategy increased its ventilator supply capacity 17 times in 10 months. However, the absence of essential certifications in 95.52% of the premarket submissions, such as the Certificate of Conformity issued by the Brazilian Conformity Assessment System (CC-SBAC), raised safety and performance concerns. Among temporarily approved ventilators, the main cause of cancellation (76.92%) was the absence of certifications after the temporal approval, notwithstanding the already installed devices maintaining authorization for use in health services. Postmarket alerts lacked CC-SBAC issuance in 75% of the cases when sponsors reported the occurrences. It highlighted the importance of ongoing technical assistance and monitoring, particularly for devices lacking proper certifications. Conclusions: The extraordinary regulatory conditions in Brazil significantly impacted ventilator premarket evaluation. However, lacking essential certifications led to post-approval cancellations. Postmarket occurrences emphasized necessary vigilance, with most alerts involving uncertified devices. Improved premarket evaluation, considering component shortages and real-world usage scenarios, as collaborative efforts from other countries and international bodies, is crucial for ensuring the safety and effectiveness of ventilators in public health emergencies.

An FDA Guide on Indications for Use and Device Reporting of Artificial Intelligence-Enabled Devices: Significance for Pediatric Use

Radiology has been a pioneer in adopting artificial intelligence (AI)-enabled devices into the clinic. However, initial clinical experience has identified concerns of inconsistent device performance across different patient populations. Medical devices, including those using AI, are cleared by the FDA for their specific indications for use (IFUs). IFU describes the disease or condition the device will diagnose or treat, including a description of the intended patient population. Performance data evaluated during the premarket submission support the IFU and include the intended patient population. Understanding the IFUs of a given device is thus critical to ensuring that the device is used properly and performs as expected. When devices do not perform as expected or malfunction, medical device reporting is an important way to provide feedback about the device to the manufacturer, the FDA, and other users. This article describes the ways to retrieve the IFU and performance data information as well as the FDA medical device reporting systems for unexpected performance discrepancy. It is crucial that imaging professionals, including radiologists, know how to access and use these tools to improve the informed use of medical devices for patients of all ages.

Development of a Patient Preference Survey for Wearable Kidney Replacement Therapy Devices.

Recent innovations have the potential to disrupt the current paradigm for kidney failure treatment. The US Food and Drug Administration is committed to incorporating valid scientific evidence about how patients weigh the benefits and risks of new devices into their decision making, but to date, premarket submission of patient preference information (PPI) has been limited for kidney devices. With input from stakeholders, we developed a survey intended to yield valid PPI, capturing how patients trade off the potential benefits and risks of wearable dialysis devices and in-center hemodialysis. We conducted concept elicitation interviews with individuals receiving dialysis to inform instrument content. After instrument drafting, we conducted two rounds of pretest interviews to evaluate survey face validity, comprehensibility, and perceived relevance. We pilot tested the survey with in-center hemodialysis patients to assess comprehensibility and usability further. Throughout, we used participant input to guide survey refinements. Thirty-six individuals receiving in-center or home dialysis participated in concept elicitation (N=20) and pretest (N=16) interviews. Participants identified reduced fatigue, lower treatment burden, and enhanced freedom as important benefits of a wearable device, and many expressed concerns about risks related to device disconnection-specifically bleeding and infection. We drafted a survey that included descriptions of the risks of serious bleeding and serious infection and an assessment of respondent willingness to wait for a safer device. Input from pretest interviewees led to various instrument modifications, including treatment descriptions, item wording, and risk-level explanations. Pilot testing of the updated survey among 24 in-center hemodialysis patients demonstrated acceptable survey comprehensibility and usability, although 50% of patients required some assistance. The final survey is a 54-item web-based instrument that will yield estimates of the maximal acceptable risk for the described wearable device and willingness to wait for wearable devices with lower risk.

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

The U.S. Food and Drug Administration (FDA) has been concerned with minimizing the unnecessary radiation exposure of people for half a century. Manufacturers of medical X-ray imaging devices are important partners in this effort. Medical X-ray imaging devices are regulated by FDA under both its electronic product regulations andits medical device regulations. FDA also publishes guidance documents that represent FDA's current thinking on a topic and provide a suggested or recommended approach to meet the requirements of a regulation or statute. FDA encourages manufacturers to develop medical devices that conform to voluntary consensus standards. Use of these standards is a central element of FDA's system to ensure that all medical devices marketed in the U.S. meet safety and effectiveness requirements. FDA staff participate actively in the development and maintenance of these standards, often advancing or introducing new safety and dose management requirements. Use of voluntary consensus standards reduces the amount of time necessary to evaluate a premarket submission and reduces the burden on manufacturers. FDA interacts with industry and other stakeholders through meetings with industry groups, public meetings, public communications, and through the development of voluntary consensus standards. In these interactions, FDA staff introduce new concepts for improving the safety of these devices and provide support for similar initiatives from professional organizations. FDA works with all stakeholders to achieve its mission of protecting and promoting the public health.

Regulation of orthopaedic devices: Future implications for research and innovation.

The conception-to-market development of orthopaedic devices occurs across the total product life cycle including device design and preclinical testing, clinical investigations to support marketing applications, and monitoring of device performance after market introduction. This process involves industry, regulatory agencies, health care providers, engineers, scientists, and patients. The Food and Drug Administration (FDA) is responsible for regulating medical devices in the United States, and uses a 3-tier classification system based on the level of control necessary to provide reasonable assurance of safety and effectiveness. Classification directs the required regulatory pathway and premarket submission type. Variations in global regulations, particularly between the United States, European Economic Area (EEA), and the United Kingdom (UK), may impact industry response to orthopaedic device development. Changing device innovation and reimbursement models have led to the consolidation of market share among larger companies. Although larger companies are better able to cope with more rigorous regulatory requirements, this leads to decreased competition and increased upward price pressure. To assist with the complex regulatory processes, the FDA offers pre-submission assistance as an opportunity for early collaboration and discussion about the medical device or device-led combination product submissions. Orthopaedic organizations, such as the Orthopaedic Trauma Association (OTA), may assist in postmarket device surveillance through the coordinated development and maintenance of clinical data registries. Such registries can longitudinally follow patients with a specific orthopaedic pathology or device usage, and monitor outcomes towards improvements in next-generation device development. As technology evolves, the nexus of regulation, industry, and patient outcome monitoring will continue to support safe and effective device innovation.

ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices): The evolution of a collaborative regional CTSA-funded forum and website for regulatory support.

Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.

Qualification of a non-animal vaginal irritation method admitted as nonclinical assessment model (NAM) in the Incubator Phase of the United States Food and Drug Administration (US FDA) Medical Devices Development Tool (MDDT)

The U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) classifies personal lubricants as Class II medical devices. Because of this status and the nature of body contact common to personal lubricants, CDRH reviewers routinely recommend a standard biocompatibility testing battery that includes: an in vivo rabbit vaginal irritation (RVI) test; an in vivo skin sensitization test, such as the guinea pig maximization test (GPMT); and an in vivo acute systemic toxicity test using mice or rabbits. These tests are conducted using live animals, despite the availability of in vitro and other non-animal test methods that may be suitable replacements. The only test included in the biocompatibility battery currently conducted using in vitro assay(s) is cytotoxicity. FDA's recently launched Predictive Toxicology Roadmap calls for the optimization of non-animal methods for the safety evaluation of drugs, consumer products and medical devices. In line with these goals, a Consortium comprising the Institute for In Vitro Sciences, Inc. (IIVS), industry, the Consumer Healthcare Products Association (CHPA), and the PETA International Science Consortium (PETA-ISC) is qualifying the use of an in vitro testing method as replacement for the RVI test. Participating companies include manufacturers of personal lubricants and those interested in the advancement of non-animal approaches working collaboratively with the FDA CDRH to develop an in vitro testing approach that could be used in place of the RVI in pre-market submissions. Personal lubricants and vaginal moisturizers with diverse chemical and physical properties (e.g., formulation, viscosity, pH, and osmolality) in their final undiluted form will be the focus of the program. In vitro vaginal irritation data generated using commercially available human reconstructed vaginal tissue model(s) will be paired with existing in vivo RVI data and analyzed to develop a Prediction Model for the safety assessment of these products. This research plan has been accepted into the FDA CDRH Medical Device Development Tools (MDDT) program as a potential non-clinical assessment model (NAM). The proposed NAM aligns with the goals of the recently launched FDA Roadmap to integrate predictive toxicology methods into safety and risk assessment with the potential to replace or reduce the use of animal testing.

Considering the Dynamics of FDA Human Factors ValidationRequirement: Implications of Failure and Need to Ensure ProjectSuccess - A Conceptual Framework

Recognizing the role of human factors engineering (HFE) in the development of medical devices and combination products that involve devices, the Food and Drug Administration (FDA) now requires human factors (HF) validations before market approval. Manufacturers are responsible for ensuring their products are safe and effective through the application of HFE. However, key stakeholders are still learning and developing capabilities to adapt to the regulatory component. Nonetheless, the lack of the corresponding HF capabilities hinders compliance with the FDA’s expectations, and though ultimate success. No known previous work has looked into FDA HF validation projects to assess the underlying factors and implications of failed submissions. Applying system dynamics (SD), a causal loop diagram (CLD) was developed. CLDs are useful for the exploration of the causal interactions among factors or variables, as well as the underlying feedback structure of a complex system. This work can serve to help manufacturers better understand the FDA’s HF requirement to enable overall product success. Further, with patient safety as a common goal, HF service providers (HFSPs) and regulators should be aware of the need to ensure the consistent quality of the HF element in premarket submissions.

Statistical Methods for Clinical Study Site Selection

The US Food and Drug Administration conducts on-site inspections and data audits through Bioresearch Monitoring program for assurance of the quality and integrity of data in the pre- and postapproval processes. It is important to inspect the study sites that are different compared with other sites in clinical studies and identify the problems related to those sites. Usually one cannot inspect all the sites in a clinical study because of limited resources, and statistical tools are needed to help in selecting sites for inspection. We propose two technical approaches, namely Fisher combination approach and likelihood ratio test (LRT) approach, for site selection, with each approach integrating the information obtained from a P value matrix. The proposed approaches produce site rankings, and the sites with highest rankings may be selected for inspection. The application of the approaches is demonstrated through a hypothetical data set reflecting the pattern of the real data in a premarket approval submission for a diagnostic device. The proposed methods are shown, through extensive simulations, to control false discovery rate, while maintaining good sensitivity. The proposed approaches will be useful for site selection process. However, limitations exist when only using the statistical approaches proposed here. In practice, investigators will select the site for inspection by considering the outputs from the statistical approaches along with other important factors. Future research topic is discussed to facilitate practical application of the approaches.

Over-the-counter light therapy for acne: a cross-sectional retrospective analysis

Acne vulgaris affects a large portion of the population and drives many patients to seek over-the-counter (OTC) treatments. Light-emitting diode (LED) therapy has recently emerged as a potential therapeutic option for inflammatory acne. We used the U.S. Food and Drug Administration (FDA) 510(k) premarket submission database to assess the growth in OTC LED therapy devices for treatment of acne. We also used Google Trends data in searches for "acne light therapy mask" to characterize growth in consumer interest in these devices. Overall, 35 LED devices received pre-market approval from 2000 to 2018, with a peak in approvals in 2016. Similarly, there was a dramatic increase in public interest in these devices in 2016. Only two devices were associated with company-approved trials. The current regulatory process requires little evidence to substantiate specified uses and a better understanding of practice guidelines and the efficacy of this treatment modality is required.

Under-Reporting of Patient Reported Outcome (PRO) in Clinical Trials

Introduction: Clinically relevant outcomes as improvements in overall survival (OS) or quality of life (QOL) should guide decision-making. The FDA encourages the implementation of patient-centric PRO measures in clinical trials. In the recent decade there have been a growing number of protocols including PROs in their outcome measures, and an increase in pre-market submissions including those measures. We aimed to evaluate the frequency at which PRO measures, incorporated into clinical trials, are made publicly available, when trial results are published.Methods: We searched Citeline® Trialtrove database, a registry of clinical trials, for randomized phase 2/3 and 3 clinical trials including patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), initiated between the years 2005-2015, with PRO endpoints listed. We excluded trials involving patients with acute leukemia or involving stem cell transplantation. For these trials we recorded the following data: indication, treatment and comparator, phase, primary endpoint, type of scale or questionnaire used for PRO endpoint. We then identified all available publications associated with the trial, and recoded type of publication (abstract or full text), year, number of randomized patients, reported outcomes.Results: 120 CLL and NHL trials were identified through our search. 44 trials (23 CLL, 21 NHL) were listed with at least one PRO endpoint. Eleven trials were excluded (1 extension of an included trial, 4 not completed, 4 not published, 2 cancelled with little or no recruitment). PRO endpoints were assessed utilizing - EORTC-QLQ30 QoL, QLQ-CLL16, FACIT-fatigue, FACT-leu, FACT-lym, EQ-5D, Skindex-29, and Rituximab Administration Satisfaction Questionnaire as relevant per indication. PRO was the primary outcome in two trials, and secondary in the other 31. Study sponsor was industry-only in 27 trials, and industry-academic in five. Of the 33 trials analyzed, 14 (42%) published results of the PRO endpoint - 6/17 (35%) of CLL trials, and 8/16 (50%) of NHL trials. 26/33 of the trials were published as full-text, 6/33 as abstract, and 1 published on clinicaltrials.gov. Of the 26 full text publications, 12 (46%) reported PRO. In 8 of full-text PRO were reported as part of the primary publication or published within 6 months. Nine of all trials provided a comprehensive report of PRO endpoints. Of the 33 trials, only 2 provided information about missing PRO data. 54% of trials in which primary endpoint was reached, and 12.5% of trials in which it was not reached, were published listing PRO results. Of the trials that showed PFS benefit, with no OS benefit, 9/15 (60%) published the results of the PRO endpoints.Conclusions: Despite a growing emphasis on QOL and use of PROs in oncology clinical trials, and despite patient and health provider efforts to record PRO data, most CLL and NHL randomized trials still do not report the PRO endpoints. In several cases they were published later and in a partial manner, minimizing their impact on treatment decisions. This may indicate a disregard to PRO data collected, incomplete collection or methodological flaws in data analysis. Regardless of the reason, PRO data should be routinely included in study publications to allow for a complete assessment of investigational treatment outcome - including disease related outcomes, as well as those reported by the patients themselves. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

FDA-CMS Parallel Review – a failed attempt at spurring innovation

Purpose The purpose of this paper is to analyze the Parallel Review program that offers simultaneous review of the Food and Drug Administration premarket approval submissions and the Centers for Medicare and Medicaid Services (CMS) national coverage determinations (NCDs) of medical devices. Design/methodology/approach The paper analyzes the impact of Parallel Review on medical device innovation, focusing in particular on the causes for low popularity of the program among medical device manufacturers. Program outcomes are evaluated in the light of its intended goals. Findings The paper identifies four reasons for the program’s limited impact. First, few devices are eligible to participate. Second, most manufacturers prefer to seek Medicare reimbursement at the local level as less risky than the CMS NCDs. Third, participation in the Parallel Review might actually delay the marketing of the device. Fourth, the program does not address numerous obstacles that device sponsors currently encounter. While giving the appearance of support for the medical device innovation, the policy falls short on its intended goals. Originality/value This paper elucidates the challenges to internal reform and serves as a reminder to political economists and health care researchers that to make disruptive innovation possible, we must continue to illuminate the otherwise unseen cost of marketing delays and document the ability of emergent market mechanisms to protect consumer safety.

Retrospective analysis of RF heating measurements of passive medical implants.

The test reports for the RF-induced heating of metallic devices of hundreds of medical implants have been provided to the U.S. Food and Drug Administration as a part of premarket submissions. The main purpose of this study is to perform a retrospective analysis of the RF-induced heating data provided in the reports to analyze the trends and correlate them with implant geometric characteristics. The ASTM-based RF heating test reports from 86 premarket U.S. Food and Drug Administration submissions were reviewed by three U.S. Food and Drug Administration reviewers. From each test report, the dimensions and RF-induced heating values for a given whole-body (WB) specific absorption rate (SAR) and local background (LB) SAR were extracted and analyzed. The data from 56 stents were analyzed as a subset to further understand heating trends and length dependence. For a given WB SAR, the LB/WB SAR ratio varied significantly across the test labs, from 2.3 to 11.3. There was an increasing trend on the temperature change per LB SAR with device length. The maximum heating for stents occurred at lengths of approximately 100 mm at 3 T, and beyond 150 mm at 1.5 T. Differences in the LB/WB SAR ratios across testing labs and various MRI scanners could lead to inconsistent WB SAR labeling. Magnetic resonance (MR) conditional labeling based on WB SAR should be derived from a conservative estimate of global LB/WB ratios.

Translational research of one dynamic hip screw system—from the SCI to the FDA

SummaryBackground/objectiveWhen researchers or developers wish to apply their findings to clinical usages, it must be approved by public authorities such as the US Food and Drug Administration (FDA). In addition to the development records and risk control documents, all of the materials and testing must be completed by laboratories or manufacturers with good quality controls in accordance with related regulations or standards. The Orthopaedic Device Research Center dynamic hip screw system (ODRC-DHS system), which was developed by the ODRC, National Yang-Ming University, Taipei, Taiwan, obtained FDA 510(k) clearance in 2011.MethodsThe application process was divided into five steps: (1) make sure that the product is a medical device and classify it; (2) find the predicate devices cleared by the FDA; (3) research any standards and/or guidance documents; (4) prepare the appropriate information for premarket submission to the FDA; and (5) send premarket submission to the FDA and interact with the FDA staff.Results and ConclusionThe relevant regulations, guidelines, and strategies were detailed by step-by-step demonstration so that readers can quickly understand the requirements and know-how of a translational research.

Point-Counterpoint: The FDA Has a Role in Regulation of Laboratory-Developed Tests.

Since the Food and Drug Administration (FDA) released its draft guidance on the regulation of laboratory-developed tests (LDTs) in October 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. The FDA defines an LDT as an "in vitrodiagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory." The draft guidance outlines a risk-based approach, with oversight of high-risk and moderate-risk tests being phased in over 9 years. High-risk tests would be regulated first and require premarket approval. Subsequently, moderate-risk tests would require a 510(k) premarket submission to the FDA and low-risk tests would need only to be registered. Oversight discretion would be exercised for LDTs focused on rare diseases (defined as fewer than 4,000 tests, not cases, per year nationally) and unmet clinical needs (defined as those tests for which there is no alternative FDA-cleared or -approved test). There was an open comment period followed by a public hearing in early January of 2015, and we are currently awaiting the final decision regarding the regulation of LDTs. Given that LDTs have been developed by many laboratories and are essential for the diagnosis and monitoring of an array of infectious diseases, changes in their regulation will have far-reaching implications for clinical microbiology laboratories. In this Point-Counterpoint, Angela Caliendo discusses the potential benefits of the FDA guidance for LDTs whereas Kim Hanson discusses the concerns associated with implementing the guidance and why these regulations may not improve clinical care.

Special Commentary: Food and Drug Administration and American Glaucoma Society Co-sponsored Workshop: The Validity, Reliability, and Usability of Glaucoma Imaging Devices

of optic nerve structure and function is the basis for the diagnosis and management of glaucoma. 2,3 Advances in computerized imaging devices to assess the anatomy of the optic nerve complex (retinal ganglion cell layer, retinal nerve fiber layer [RNFL], optic disc, and parapapillary region) are improving our understanding of glaucomatous neurodegeneration and may ultimately be shown to result in improved outcomes for patients. Over the past decade, there has been a significant increase in the number of premarket submissions for imaging devices received by the US Food and Drug Administration (FDA), which has been accompanied by a dramatic rise in the use of ocular imaging devices in the management of glaucoma. 4 As with any diagnostic device, appropriate use can enhance patient care, and inaccurate classification or misinterpretation of results can lead to a delay in diagnosis or unnecessary treatment and associated patient anxiety, increased costs, and risks associated with unnecessary treatments. In light of these concerns about the appropriate use of these devices in ophthalmic care, the FDA and the American Glaucoma Society sought expert opinions on ways to facilitate the correct use of these devices and to promote innovation in this device area. OnOctober5,2012,theFDAandtheAmericanGlaucoma Society co-sponsored a workshop at the FDA’s Silver Spring campus to discuss imaging devices used in the diagnosis and management of glaucoma with an emphasis on optical coherence tomography (OCT) devices. 5 The specific goals of the workshop were to provide a platform for physicians, researchers, and FDA colleagues interested in the field of imaging devices for glaucoma to discuss the construction, reliability, and usability (what to convey to the user) of normative databases; to enhance the proper use of these databases and imaging technologies in clinical practice; to elucidate approaches to evaluate the accuracy, agreement, and precision of measurements; and to advance and clarify the regulatory science in the field of imaging devices. The workshop agenda with links to the speaker’s slides, a transcript of the workshop proceedings, and the Webcast of the workshop are available online at the FDA website (available at: http://www.fda.gov/MedicalDevices/ NewsEvents/WorkshopsConferences/ucm318305.htm# agenda).

Challenges in the characterization of high intensity therapeutic ultrasound devices and fields and regulatory guidance development

As part of its regulatory responsibility for medical devices, the US Food and Drug Administration (FDA), Center for Devices and Radiological Health, reviews pre-clinical and, if necessary, clinical data submitted by device applicants relevant to safety, effectiveness, and accurate labeling. For HITU devices, pre-clinical testing can include ultrasound power measurement, pressure/intensity mapping, temperature field characterization (in vitro and in vivo), acoustic and thermal simulations, and demonstration of the targeting accuracy and treatment monitoring. To assist manufacturers and third parties in the submission process, the FDA provides pre-market submission guidance that often relies on technical standards and specifications such as published by the International Electrotechnical Commission (IEC). IEC documents for HITU are currently nearing completion. However, even with these documents, technical challenges remain because of the focused, large amplitude pressure fields encountered in HITU. Measurement and modeling issues include using radiation force balances at HITU power levels, the need for complex deconvolution with some hydrophone types, validation of simulation models, tissue-mimicking material development for temperature measurements, and cavitation detection and quantification. These challenges along with current FDA guidance efforts will be discussed.

How Does Medical Device Regulation Perform in the United States and the European Union? A Systematic Review

Policymakers and regulators in the United States (US) and the European Union (EU) are weighing reforms to their medical device approval and post-market surveillance systems. Data may be available that identify strengths and weakness of the approaches to medical device regulation in these settings. We performed a systematic review to find empirical studies evaluating medical device regulation in the US or EU. We searched Medline using two nested categories that included medical devices and glossary terms attributable to the US Food and Drug Administration and the EU, following PRISMA guidelines for systematic reviews. We supplemented this search with a review of the US Government Accountability Office online database for reports on US Food and Drug Administration device regulation, consultations with local experts in the field, manual reference mining of selected articles, and Google searches using the same key terms used in the Medline search. We found studies of premarket evaluation and timing (n = 9), studies of device recalls (n = 8), and surveys of device manufacturers (n = 3). These studies provide evidence of quality problems in pre-market submissions in the US, provide conflicting views of device safety based largely on recall data, and relay perceptions of some industry leaders from self-surveys. Few studies have quantitatively assessed medical device regulation in either the US or EU. Existing studies of US and EU device approval and post-market evaluation performance suggest that policy reforms are necessary for both systems, including improving classification of devices in the US and promoting transparency and post-market oversight in the EU. Assessment of regulatory performance in both settings is limited by lack of data on post-approval safety outcomes. Changes to these device approval and post-marketing systems must be accompanied by ongoing research to ensure that there is better assessment of what works in either setting.

Meet the Human Factors Pre-Market Review Team from FDA (HFES'11 Healthcare Technical Group Invited Address)

The session will introduce you to FDA’s process, priorities, and rationale for reviewing human factors content in pre-market submissions for new medical devices. Critical components of the review process will be highlighted: 1) the types of information FDA needs to see in a successful device submission in order to ensure prompt reviews, and 2) the types of data that provide sufficient evidence of reasonably safe and effective device use for the intended users, uses, and use environments. The presenters will also discuss FDA guidance documents, including the new and updated human factors guidance document and the human factors content contained in the new infusion pump guidance, as well as relevant national and international standards that can assist manufacturers in performing effective human factors design, evaluation and testing to ensure devices are optimally safe and effective during their use, and will also in assist in preparing the human factors component of new device submissions. The speakers wil...

Regulatory perspective on translating proteomic biomarkers to clinical diagnostics

Issues associated with the translation of complex proteomic biomarkers from discovery to clinical diagnostics have been widely discussed among academic researchers, government agencies, as well as assay and instrumentation manufacturers. Here, we provide an overview of the regulatory framework and type of information that is typically required in order to evaluate in vitro diagnostic tests regulated by the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) at the US Food and Drug Administration (FDA), with the focus on some of the issues specific to protein-based complex tests. Technological points pertaining to mass spectrometry platforms and assessment of potential concerns important for assurance of safety and effectiveness of this type of assays when introduced into clinical diagnostic use, as well as general approaches for evaluating the performance of these devices, are discussed.