Safety Of Medical Devices Research Articles

A fast in silico model for preoperative risk assessment of paravalvular leakage.

In silico simulations can be used to evaluate and optimize the safety, quality, efficacy and applicability of medical devices. Furthermore, in silico modeling is a powerful tool in therapy planning to optimally tailor treatment for each patient. For this purpose, a workflow to perform fast preoperative risk assessment of paravalvular leakage(PVL) after transcatheter aortic valve replacement (TAVR) is presented in this paper. To this end, a novel, efficient method is introduced to calculate the regurgitant volume in a simplified, but sufficiently accurate manner. A proof of concept of the method is obtained by comparison of the calculated results with results obtained from in vitro experiments. Furthermore, computational fluid dynamics (CFD) simulations are used to validate more complex stenosis scenarios. Comparing the simplified leakage model to CFD simulations reveals its potential for procedure planning and qualitative preoperative risk assessment of PVL. Finally, a 3D device deployment model and the efficient leakage model are combined to showcase the application of the presented leakage model, by studying the effect of stent size and the degree of stenosis on the regurgitant volume. The presented leakage model is also used to visualize the leakage path. To generalize the leakage model to a wide range of clinical applications, further validation on a large cohort of patients is needed to validate the accuracy of the model's prediction under various patient-specific conditions.

Proof of concept testing of a positive reference material for in vivo and in vitro sensitization testing of medical devices.

In vivo skin sensitization tests are required to evaluate the biological safety of medical devices in contact with living organisms to provide safe medical care to patients. Negative and positive reference materials have been developed for biological tests of cytotoxicity, implantation, hemolysis, and in vitro skin irritation. However, skin sensitization tests are lacking. In this study, polyurethane sheets containing 1 wt/wt % 2,4-dinitrochlorobenzene (DNCB-PU) were developed and evaluated as a positive reference material for skin sensitization tests. DNCB-PU sheet extracts prepared with sesame oil elicited positive sensitization responses for in vivo sensitization potential in the guinea pig maximization test and the local lymph node assay. Furthermore, DNCB-PU sheet extracts prepared with water and acetonitrile, 10% fetal bovine serum-containing medium, or sesame oil elicited positive sensitization responses as alternatives to animal testing based on the amino acid derivative reactivity assay, human cell line activation test, and epidermal sensitization assay, respectively. These data suggest that the DNCB-PU sheet is an effective extractable positive reference material for in vivo and in vitro skin sensitization testing in medical devices. The formulation of this reference material will lead to the development of safer medical devices that contribute to patient safety.

Testing a Cloud-Based Model for Active Surveillance of Medical Devices with Analyses of Coronary Stent Safety Using the Data Extraction and Longitudinal Trend Analysis (DELTA) System.

To demonstrate the use of the Data Extraction and Longitudinal Trend Analysis (DELTA) system in the National Evaluation System for health Technology's (NEST) medical device surveillance cloud environment by analyzing coronary stent safety using real world clinical data and comparing results to clinical trial findings. Electronic health record (EHR) data from two health systems, the Social Security Death Master File, and device databases were ingested into the NEST cloud, and safety analyses of two stents were performed using DELTA. This is an observational study of patients receiving zotarolimus drug-eluting coronary stents (ZES) or everolimus eluting coronary stents (EES) between July 1, 2015 and December 31, 2017. After exclusions, 3334 patients receiving EES and 1002 receiving ZES were available for study. Analysis using inverse probability weighting showed no significant difference in one-year mortality or major adverse cardiac events (MACE) for EES compared to ZES [Mortality Odds Ratio 0.94 (95% CI 0.81-1.175); p = 0.780] [MACE Odds Ratio 1.04 (95% CI 0.92-1.16; p = 0.551]). Analysis using propensity matching showed no significant difference in EES one-year mortality (547 of 992 alive and available after censoring) compared to ZES (546 of 992) [Log-Rank statistic 0.3348 (p = 0.563)]. Automated cloud-based medical device safety surveillance using EHR data is feasible and was efficiently performed using DELTA. No statistically significant differences in 1-year safety outcomes between ZES and EES were identified using two statistical approaches, consistent with randomized trial findings.

Exploration of Application of Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices: Take Artificial Joint Products as Example

Through the effective application of Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices (EP), to continuously improve the corresponding management tools to ensure the safety and effectiveness of medical device in the quality management system, risk management system, evaluation of safety and effectiveness for the supervision departments and manufacturers. The current status of the application of EP and the application issues are analyzed in the study. Take artificial joint products for example, the idea of using EP in quality management system, risk management system and evaluation of safety and effectiveness is investigated, and several thoughts are proposed. Supervision departments should strengthen the unified understanding of EP, develop requirements according to the classification of medical device，and refine specific execution requirements.

Ala®sil chemical characterization and toxicity evaluation: an example of the need for the Medical Device Regulation 2017/745.

Introduction: Ala®sil infusion was on the market for clinical use under the Medical Devices Directive (MDD) 93/42/EEC as an irrigating solution based on polydimethylsiloxane (PDMS). The product was withdrawn in 2016, and to the best of our knowledge, it did not cause any health damage. Methods: A bibliographic review and experimental analysis were conducted to evaluate whether this CE-marked product could have been used in patients under the current Medical Device Regulation (MDR) 2017/745. Analytical results from gas chromatography-mass spectrometry (GC-MS) and matrixassisted laser desorption ionization (MALDI) were performed. Citotoxicity studies were also carried out. Results: Only one study related to Ala®sil clinical use was found, describing a pilot series of five patients. The authors rated the product as not helpful in three out of the five cases for internal searching of retinal breaks and in four out of the five cases for drainage of subretinal fluid. No other scientific papers or documentation was found regarding Ala®sil's safety. Nevertheless, the product was introduced in the market after achieving the CE marking. GC-MS and MALDI showed that the polymer has a low molecular weight of 1,000g/mol. Several linear and cyclic low-molecular-weight components (LMWCs) were identified as impurities ranging from L3 to D8, with a molecular weight below 600g/mol. The Ala®sil sample was found to be cytotoxic after 24h of cell culture but non-cytotoxic after 72h, probably due to the cellular regeneration capacity of an immortalized cell line. Tissular cytotoxicity revealed an increased apoptosis rate but without morphological modifications. Discussion: Although Ala®sil cannot be classified as cytotoxic, this substance appears to increase retinal cell death processes. This study supports the notion that the MDDwas not functioning adequately to ensure the safety of medical devices. However, the current MDR 2017/745 imposes stricter standards to prevent the commercialization of medical devices without high-quality preclinical and clinical information, as well as precise clinical verification for their use, information not available for Ala®sil infusion.

The "Big Three" in biocompatibility testing of medical devices: implementation of alternatives to animal experimentation-are we there yet?

Biocompatibility testing ensures the safety of medical devices by assessing their compatibility with biological systems and their potential to cause harm or adverse reactions. Thus, it is a critical part of the overall safety evaluation process for medical devices. Three primary types of biocompatibility tests-cytotoxicity, irritation, and sensitisation assessment-are standard for nearly all medical devices. However, additional biocompatibility tests, such as genotoxicity, systemic toxicity, hemocompatibility, and implantation studies, may also be necessary, depending on the device's nature and intended use. The testing is partly conducted in vitro, but the industry still heavily relies on animal experiments. Compared to other industrial sectors, implementing alternatives in medical device biocompatibility testing has been notably slower. This delay can be attributed to the absence of specific validation processes tailored to medical devices and the resulting hesitation regarding the predictive capacity of these alternative methods despite their successful applications in other domains. This review focuses on the progress and obstacles to implementing new approach methodologies in the areas of cytotoxicity, irritation and sensitisation testing of medical devices. While challenges persist in adopting these innovative methods, the trend towards embracing alternatives remains robust. This trend is driven by technological advancements, ethical considerations, and growing industrial interest and support, all collectively contributing to advancing safer and more effective medical devices.

A Brief Review on Pharmacovigilance

Clinical Research: Clinical research refers to the scientific investigation conducted to understand, prevent, diagnose, or treat human diseases and conditions. It involves the systematic study of individuals, often through clinical trials, to generate evidence-based knowledge that can advance medical understanding and improve patient care. Clinical research plays a crucial role in the development of new medical interventions, therapies, and healthcare strategies. Clinical Trials: Clinical trials are a specific form of clinical research designed to evaluate the safety and efficacy of medical interventions, including drugs, devices, treatments, and preventive measures. These trials are conducted in phases, each serving a distinct purpose in the research process.

Development of a Comprehensive Regulatory Model for Medical Devices

Abstract Background: The development of a comprehensive regulatory model for medical devices is essential to ensure the safety, efficacy, and quality of medical devices throughout their lifecycle, from design and development to post-market surveillance. This paper outlines a robust framework for such a regulatory model, detailing key components and processes necessary for effective regulation. Methods: The data and literature were collected from various databases including Springer, Science Direct, Taylor and Francis, Wiley, Bentham Science, and websites of different regulatory agencies. The collected data were utilized in the research work to formulate the new regulatory model. Results: Different guidelines represent acceptable regulatory practices for all medical items. There are four risk classification levels of the medical devices (class I–IV, based on the risk level). For every country, the regulatory requirements are different. Global regulations for medical device approval are essential to guaranteeing their quality, safety, efficacy, and performance before they can be put on the market to safeguard, prevent, enhance, and maintain public health. Different classes have different regulatory steps for approval of the devices, which varies from region to region. The World Health Organization’s Department of Essential Health Technologies’ Diagnostic Imaging and Medical Devices team has developed and implemented the Baseline Country Survey on Medical Devices. The proposed model includes the establishment of a clear legislative and regulatory framework, featuring a risk-based classification system aligned with international standards. It emphasizes rigorous pre-market requirements, including design controls, clinical evaluation, quality management systems, and technical documentation. Market authorization processes are described, highlighting pathways such as Premarket Notification (510(k)), Premarket Approval (PMA), and De Novo Classification, supported by thorough scientific review and expert advisory panels. The present study is all about the global requirements of the regulation of the medical devices and it was concluded that overall, a global comprehensive regulatory model for medical devices aims to strike a balance between ensuring patient safety, facilitating innovation, and enabling timely access to life-saving medical technologies around the world. Conclusion: The model advocates for international harmonization and collaboration, promoting regulatory convergence and the adoption of global standards. It also supports innovation through accelerated approval pathways and regulatory sandboxes, alongside continuous improvement driven by regulatory science research and stakeholder engagement. By integrating these elements, the comprehensive regulatory model aims to protect public health while fostering medical device innovation and ensuring global regulatory compatibility.

Navigating regulatory landscape: A qualitative exploration of medical devices and in vitro diagnostic medical devices oversight in Zimbabwe through key stakeholder perspectives.

Medical devices and In Vitro Diagnostics (IVDs) are vital for public health and accessible healthcare. Still, there is an imbalance in high-quality products in Low and Middle-Income Countries (LMICs). Zimbabwe's regulatory framework for medical devices and IVDs is unclear, leading to ineffective compliance and surveillance. As a result, there are knowledge gaps regarding pre-market and post-market regulatory elements to ensure the safety, quality and performance of medical devices and IVDs used in Zimbabwe. Our study aimed to explore the current status of medical devices and IVD regulations in Zimbabwe. Semi-structured interviews were conducted with 12 regulators from the Medicines Control Authority of Zimbabwe (MCAZ) National Microbiology Reference Laboratory (NMRL), Medical Laboratory and Clinical Scientists Council (MLCScCZ) to understand the current status of medical devices and IVD regulations in Zimbabwe. Three participants completed a questionnaire to understand the regulatory landscape in Zimbabwe. Three key informant interviews were conducted with three regulators from the South African Health Products Regulatory Authority (SAHPRA), Tanzanian Medicines and Medical Devices Authority (TMDA), and World Health Organization Regulatory Systems Strengthening (WHO RSS) to learn best practices to create a roadmap for Zimbabwe. We analyzed qualitative data using a thematic analysis. The findings reveal significant deficiencies and gaps in the legal framework for regulating medical devices and IVDs, highlighting the need for a legal framework and the absence of more comprehensive regulations. Regulatory entities face capacity limitations, especially in regulating medical devices and IVDs. Conformity assessment processes, medical devices, IVD classification criteria, and post-market surveillance also represent challenges, highlighting the need for a well-defined framework and regulatory procedures. The Zimbabwean regulatory system pathway is reactive, prompting several regulatory initiatives to address needs. Despite facing challenges, there is recognition of the importance of collaboration among regulatory authorities, emphasizing a shared commitment to improving and strengthening medical devices and IVD regulations for improved patient safety. By advocating for a proactive, comprehensive, and legally sound approach, indicating the potential for collaboration and synergy, this study provides a foundation for well-informed policy recommendations to guide enhancements and build a framework for a resilient, efficient, and transparent regulatory environment in the Zimbabwe and African regions as a whole.

Advancing In Silico Clinical Trials for Regulatory Adoption and Innovation.

The evolution of information and communication technologies has affected all fields of science, including health sciences. However, the rate of technological innovation adoption by the healthcare sector has been historically slow, compared to other industrial sectors. Innovation in computer modeling and simulation approaches has changed the landscape in biomedical applications and biomedicine, paving the way for their potential contribution in reducing, refining, and partially replacing animal and human clinical trials. In Silico Clinical Trials (ISCT) allow the development of virtual populations used in the safety and efficacy testing of new drugs and medical devices. This White Paper presents the current framework for ISCT, the role of in silico medicine research communities, the different perspectives (research, scientific, clinical, regulatory, standardization, data quality, legal and ethical), the barriers, challenges, and opportunities for ISCT adoption. In addition, an overview of successful ISCT projects, market-available platforms, and FDA- approved paradigms, along with their vision, mission and outcomes are presented.

Application of Global Trigger Tools in University Hospital and Comparison to Volunteer Adverse Events Reporting System.

A voluntary reporting system (VRS) is still used to detect adverse events (AEs) in health-care services in many countries. We attempted to apply the Global Trigger Tool (GTT) for the first time in our country and searched for an answer to the question of whether there could be new triggers. Two hundred and forty inpatient records were selected from total of 1,807 inpatient files in the university obstetrics and gynecology clinic between 2018 and 2020. Twenty files per month were reviewed retrospectively using GTT, an approach developed by the American Institute for Health Development. VRS records of the same period were examined. The data were evaluated according to the National Coordinating Council for Medication Error Reporting and Prevention scale and those in the E, F, G, H, I categories were included. The number of AEs per 1,000 patient days was 47.81, AEs per 1,000 patient hospitalizations was 95.83, and hospitalizations with AEs was 9.58%. In the VRS data, 10 of 85 reporting cases were listed in the E category (Damage is temporary and requires intervention), 6 of them were related to fall of the patient, and 4 of them were related to medical device and material safety. By applying GTT, 45 cases in category E and 35 cases in category F (Damage is temporary and requires hospitalization or prolonged hospitalization) AEs were detected in 23 patients (9.58%). The number of AEs reported was 8.3 times higher in the GTT than with VRS. Healthcare related infection, development of complications from any procedure, APTT>100 Seconds, INR>6, Organ Injury - Repair or Removal, All Kinds of Operative Complications were found to be the most sensitive triggers (PPV = 100). There was no difference between the patients with and without AEs in terms of age and number of hospitalization days (p: 0.707, p: 0.618). The sensitivity rate of vaginal dinoprostone use and CRP elevation (30% and 22%, respectively) was higher than the mean sensitivity rate of GTT triggers (15.6%). The GTT is more effective than VRS in detecting AEs. Using vaginal dinoprostone (propess) and high CRP levels could be used as a trigger. The GTT is a credible and fruitful instrument for determining AEs when adapted to the departmental practices.

On the Relationship Between Impedances of Active Implantable Medical Devices and Device Safety Under MRI RF Emission

Impedances of different portions of active implantable medical devices (AIMDs) can influence its magnetic resonance imaging (MRI) radio-frequency (RF) safety dramatically. To better understand this behavior, in this article, we analytically derive relationships between the impedances of AIMDs and the MRI RF safety. Numerical simulations and measurements are performed to validate the proposed relationships. In addition, effective measurement setups for the AIMD impedances are proposed. The analysis in this article gives a clear design strategy for MR-conditional safe AIMDs.

Temporal trends in medical device implant procedures in Australia 2008-22: evidence from the Australian Institute of Health and Welfare National Hospital Morbidity database.

ObjectiveExamine the temporal trends in medical device implant procedures in the Australian population.MethodsWe used data from the Australian Institute of Health and Welfare from the financial years 2007-08 to 2021-22 and chose the most frequently performed medical device implant procedures. We estimated the annual change in volume of procedures and age-standardised rates by calculating the compound annual growth rate (CAGR), and used regression with the Newey-West robust variance estimator to examine whether there was a linear trend in the age-standardised rates for each procedure.ResultsFor procedures including cardiac pacemakers, heart valves, hip and knee arthroplasties, and intraocular lenses, the crude CAGR was over 3%. For the age-standardised rates, the CAGR was largest for cardiac pacemaker, followed by heart valve replacement and hip arthroplasty procedures. For some procedures, the growth was more than in the Australian population, including cardiac pacemakers (β=1.00; 95% CI: 0.14-1.86), heart valve replacements (β=0.41; 95% CI: 0.28-0.54), hip arthroplasty (β=3.50; 95% CI: 1.61-5.38), and knee arthroplasty (β=4.31; 95% CI: 0.54-8.09) procedures. The trend of standardised rates of procedures, including incisional hernia with mesh, breast implants, coronary stents, and cardiac defibrillators, grew at the same rate as the population, whereas the rate for gastric banding procedures decreased (β=-3.14; 95% CI: -4.92 to -1.34).ConclusionThe findings from the current study, showing a large increase in medical device implant procedures, will assist in future healthcare planning and efforts in post-market surveillance of safety of medical devices.

Comparison of Excipients in Approved Parenteral Products and Their Maximum Daily Exposure Values.

The following article analyses the excipients used in the parenteral formulations registered by the U.S. Food and Drug Administration (FDA) in the years 2011 and 2021. It adds real-word data for parenteral excipients in approved products from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) and the Irish Health Products Regulatory Authority (HPRA) in 2021. Maximum daily exposures (MDEs) for all parenteral excipients that had their amount listed either in the Medsafe or HPRA database are presented. Altogether, there were 355 excipients found in the parenteral dosage forms across all markets (US, New Zealand, and Ireland). Only 90 excipients (25.3%) were found in all three markets. In contrast, there were 187 (52.7%) excipients found in only one market. The MDE values of parenteral excipients from New Zealand and Ireland are frequently higher than the values found in the FDA inactive ingredients database (IID), adding important new information when the toxicity of these excipients is considered. There is a heterogenicity between the markets in use of parenteral excipients, with the US market leading in the number of total excipients as well as excipients present only in the US market. Nevertheless, there are several excipients not found in the US market that are registered in other markets. The comprehensive listing of parenteral excipients used worldwide presented in this article enables formulation scientists to quickly reference all potential parenteral excipients that are already proven safe and acceptable when designing a new parenteral formulation. Further, a list of new values for the MDE, often higher than those listed in the IID, provides important information for formulation scientists and toxicologists about the potential toxicity of these excipients.

Risk Management in Medical Device Maintenance Workshops

Risk management is a critical aspect of medical device maintenance workshops, as it plays a crucial role in ensuring the safe and reliable operation of medical equipment. This paper examines the significance of incorporating effective risk management strategies in medical device maintenance workshops to minimize potential risks and harm to patients and healthcare workers. The study highlights the importance of understanding regulations, adopting best practices, and providing continuous training to effectively manage risks. By incorporating risk management into the business strategy and involving all members of the organization, potential hazards can be identified and mitigated through appropriate controls. The research objectives include identifying potential risks, developing effective risk management strategies, evaluating current practices, assessing the impact on patient outcomes and healthcare costs, and contributing to the existing body of knowledge on medical device safety and maintenance. The research methodology employed a descriptive-analytical approach, utilizing questionnaires as a data collection tool from specialists and technicians working in medical device maintenance workshops. The findings emphasize the need for comprehensive risk management practices to ensure patient safety, improve equipment functionality, and comply with regulatory requirements. By implementing these strategies, medical device maintenance workshops can protect patients from harm, reduce downtime, and enhance overall healthcare outcomes.

The Independent Medicines and Medical Devices Safety Review: Regulatory Reform and Remedies

For years, groups of patients and their families in the United Kingdom raised their concerns about three medical interventions. The first was a possible link between hormone pregnancy tests and fetal malformations and deaths; the second was the physical and neurodevelopmental impacts of in utero valproate exposure; and the third was life-changing adverse events caused by pelvic mesh implants for pelvic organ prolapse repair and stress urinary incontinence management. In response to their tireless campaigning, the Independent Medicines and Medical Devices Safety (IMMDS) Review was commissioned by the Secretary of State for Health and Social Care in 2018. The review, chaired by Baroness Cumberlege, found a catalogue of institutional, systems and structural failures within both the medical establishment and healthcare system more broadly. Drawing on the IMMDS Review findings on pelvic mesh, in this article, I consider the dire consequences when medical devices go wrong. Drawing on firsthand experience as lead researcher for the IMMDS Review, I examine some of the background, outline some key findings and reflect on the strategic changes recommended to medical device regulation and the redress prompted by the pelvic mesh scandal. In so doing, I contextualise and consider the relevant regulatory frameworks, the fundamental systems failures and the other issues identified. Three years on, this article also provides an opportunity to assess the extent to which the IMMDS Review recommendations have been successfully operationalised, as well as to take stock of the improvements that still need to be made.

A systematic review of the evidence supporting the use of surgical aortic and mitral valves: an update from the CORE MD consortium

Abstract Introduction The European Union (EU) Medical Device Regulation (MDR) 2017/745 challenges the medical community to engage with regulators, notified bodies and industry to develop transparent, rigorous and proportionate methods to evaluate the clinical safety and efficacy of medical devices and to monitor their performance. As part of the EU Horizon 2020 funded CORE-MD project, we performed a systematic review of the published scientific evidence available for surgical heart valve replacements for native aortic and mitral valve pathologies. Purpose The aim of this analysis is to review the scientific evidence available which supports the use of currently available surgical aortic and mitral valves. Methods A systematic literature review was conducted using Ovid, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). We included only surgical aortic and mitral valves that received CE Mark approval from the year 2000 onwards. We included any study of prospective design (randomised or non-randomised clinical trials of any design) in humans, published between 2000 and 2021. We excluded retrospective studies, case reports, reviews, systematic reviews, meta-analyses, and expert opinion documents. Title and abstract screening, full-text review, risk of bias evaluation and data collection were performed by two authors independently, with disagreements resolved by discussion with a third author. Results A total of 17 surgical aortic valves and 4 surgical mitral valves were identified based on the CE mark criterion (Figure 1). The initial literature search identified 4901 and 3696 potentially eligible papers in the aortic and mitral valve categories, respectively. Finally, 39 aortic and 3 mitral valve studies were included (Figure 2). The majority of included studies (90%) had a non-randomised, prospective, observational design, with 68% receiving industry funding. The median number of patients included was 295 [interquartile range (IQR): 153, 689] with a median maximum follow up of 24 months [IQR: 12, 60]. Only 50% of the identified studies had a pre-specified registered study protocol and only 5% included a power calculation to estimate the required study size. No study reported patient involvement in the study design and only 15% of studies had a comparator group. Using the ROBINS I AND II assessment tools, 90% of the included studies were classified as having a high or serious risk of bias. Conclusion The evidence available for currently used surgical aortic and mitral replacement heart valves is largely from small, industry funded, non-randomised controlled trials. The median duration of maximum follow up was only 24 months, the majority of studies were classed as having a high/serious risk of bias and only half had a pre-registered study protocol. These results highlight the limitations of the available scientific evidence supporting the surgical aortic and mitral valves used in current clinical practice.Surgical aortic and mitral valvesSummary of literature search results

Challenges Associated with Biological Safety Assessments for Drug-Device Combination Products.

Biological safety assessments for drug-device combination products involve evaluation of the drug container closure and the device constituent part. When the device constituent part is the drug delivery system as well as the drug container closure system, both device and drug-based packaging standards have been deemed applicable. Approaches used for the biological safety assessment of medical devices differ from those used for pharmaceutical packaging/delivery systems. One area of difference is the extent to which chemical characterization with toxicological assessment is used either in addition to, or in place of, biological in vivo or in vitro tests. Differences also exist in the way nonclinical studies are used to evaluate the safety of medical devices or drug delivery systems. The lack of alignment in standards and guidance has resulted in confusion over what combination of tests and methods of evaluation constitute a biological safety assessment that will meet regulatory expectations for a drug-device combination product. The intent of this article is to discuss the challenges created when the packaging or delivery system is also a device constituent part of a drug-device combination product. Suggestions are offered regarding approaches that may be useful for conducting suitable biological safety assessments for drug-device combination products.

Baseline measures for women with mesh complications accessing a pain service (as part of the London Complex Mesh Centre).

Pelvic mesh was first used for stress urinary incontinence in 1998 following which its usage rapidly expanded to include treatment of pelvic organ prolapse. Numerous complications relating to mesh insertion soon became apparent, culminating in the Independent Medicines and Medical Devices Safety: First Do No Harm Report published by Baroness Cumberlege in 2020. Following this report, the UCLH London Complex Mesh Centre funded by NHS England, was one of a small number of specialist centres set up for mesh-injured women. The Pelvic Pain service of the Pain Management Centre at UCLH provides a service for patients attending the London Complex Mesh Centre. The aim of our study was to distinguish the differing needs of mesh-injured women from those with chronic pelvic pain by comparing patient-reported outcome measures between these two cohorts. Distribution of data was calculated using the D'Agostino-Pearson normality test. Mann-Whitney tests were used to ascertain statistical difference between the two cohorts. Ethnicity was compared between groups using Fisher's exact test. Quantile regression models were used to assess whether differences in medians between groups remained after adjustment for age and ethnicity. Statistical significance was set at p < .05. Patients with mesh were significantly older than those with chronic pelvic pain and were more likely to be of white ethnicity. After adjustment for age and ethnicity, analysis revealed that bladder interference, sex interference and DAPOS A were significantly higher amongst mesh-injured women, whereas GP and hospital admissions were significantly lower. Our data shows the importance of mesh-injured women having access to pain management services with pathways of care integrated within women's and mental health services. It is essential that these programmes include support to discuss ways of returning to sexual relationships and have models to address anxiety such as graded exposure and psychological input.

The Importance of Medical Device Reporting by Health Technology Managers Before and After Recalls Are Posted

The Food and Drug Administration (FDA) performs postmarket surveillance of medical devices as part of its mission to ensure that devices remain safe and effective while they are on the market. Medical device reporting by manufacturers, user facilities, and the public plays an important role in the agency identifying and resolving medical device safety signals. User facilities are defined as a hospital, ambulatory surgical facility, nursing home, outpatient diagnostic facility, or outpatient treatment facility and do not include physician's offices. The Safe Medical Devices Act requires user facilities to report medical-device–related deaths to the FDA and the device manufacturer, to report device-related serious injuries to the manufacturer, and to submit an annual summary of all device reports to the FDA. If the manufacturer is unknown for a serious injury report, the user facility then submits the report to the FDA. Healthcare technology managers in user facilities use their expertise to recognize, communicate, and evaluate medical device concerns. This article highlights the importance of identifying and reporting medical device issues to the FDA to ensure continued safety and effectiveness of devices on the market.