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The recent passage of European Union (EU) Regulation 2017/745 on medical devices (MDs) has improved the classification of MDs and revised their approval process and the post-marketing evaluation of their safety and effectiveness, promoting transparency and post-marketing oversight in Europe. This new regulation can better ensure patient safety and provide new opportunities for therapeutic innovation. In addition, the new regulations include and define MDs made of substances or of combinations of substances (substance-based MDs: SBMDs). The impressive growth of the MD, including SBMDs, that have been marketed over the recent years has likely been a relevant factor fueling this change. MD regulation requires a major effort from both industry and regulatory bodies to comply with its provisions. Manufacturers should produce sufficient clinical evidence that an MD, under normal conditions of use, provides adequate performance and that the foreseeable risks and frequency of adverse events (AEs) have an acceptable minimum rate, taking into account the benefits provided. We describe how we implemented the post-marketing surveillance (PMS) system of SBMDs to properly deal with post-market monitoring and confirmation of safety and performance, including AEs and the benefit–risk evaluation, as required by the 2017/745 Regulation. The two pillars of this novel system are: 1) passive vigilance, i.e., spontaneous reporting and 2) active post-marketing clinical follow-up (PMCF) activities, which systematically gather, record, and analyze real-world data (RWD) on performance, quality, function, use, tolerability, and safety of an MD, collected through a dedicated, structured web platform. Active PMCF is achieved through a process of generation, validation, and administration of digital questionnaires to all stakeholders, i.e., patients, physicians, both general practitioners and specialists, and pharmacists. The technology, potential use, advantages, and limitations of this large source of RWD are also discussed. [ABSTRACT FROM AUTHOR]

Abstract Background The reporting of adverse events in medical devices (MD) is a starting point of post-market surveillance and the most common source of initial safety signals. Because MD adverse events (AE) occur globally and involve high-profile international public health crises, international regulators implanted standard codes for MDAE reporting. This study aimed to assess the application of MDAE terminology and codes by providing examples of virtual events. Methods An online survey was conducted among participants of the MD Training Program for Regulatory Authorities which provide International Medical Device Regulators Forum (IMDRF) adverse event terminology and codes, and six virtual MDAE cases. Results All 29 of the 72 participants were regulators. In all cases, most participants selected the broad (level 1) codes rather than the detailed (level 2 or level 3) codes. While responders selected a variety of codes for all annexes in case 1, over 50% of responders selected the intended codes in case 6. The codes for cause investigation were chosen more frequently than other annexes for device problem, components, and health effect. No differences were observed in code selection amongst different stakeholders. Conclusions We identified the diversification in terminology and code selection for reporting MDAEs.

Abstract Background Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils. Methods Through a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils’ use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana’s largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints. Results A total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method. Conclusions Generating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Abstract Poor-quality, substandard and falsified, medicines pose a significant public health threat, particularly in low-middle-income countries. A retrospective study was performed on Kenya's Pharmacovigilance Electronic Reporting System (2014–2021) to characterize medicine quality-related complaints and identify associations using disproportionality analysis. A total of 2767 individual case safety reports were identified, categorized into medicines with quality defects (52.1%), suspected therapeutic failure (41.6%), and suspected adverse drug reactions (6.3%). Predominantly reported were antineoplastic agents (28.6%), antivirals (11.7%), and antibacterial agents (10.8%) potentially linked to non-adherence to good manufacturing practices, inappropriate usage and supply chain degradation. Notably, analgesics (8.2%), and medical devices (3.5%) notified had quality defects, predominantly from government health facilities (60.0%). Antineoplastic agents (20.2%) and antivirals (3.7%) were frequently reported from suspected therapeutic failures and suspected adverse drug reactions, respectively, across both private for-profit facilities (26.5%) and not-for-profit facilities (5.4%). Underreporting occurred in unlicensed health facilities (8.1%), due to unawareness and reporting challenges. Pharmacists (46.1%), and pharmaceutical technicians (11.7%) predominantly reported quality defects, while medical doctors (28.0%) reported suspected therapeutic failures. Orally administered generic medicines (76.9%) were commonly reported, with tablets (5.8%) identified as potential sources of suspected adverse drug reactions, while quality defects were notified from oral solutions, suspensions, and syrups (7.0%) and medical devices (3.9%). The COVID-19 pandemic correlated with reduced reporting possibly due to prioritization of health surveillance. This study provides valuable evidence to supporting the use of medicine quality-related complaints for proactive, targeted regulatory control of high-risk medicines on the market. This approach can be strengthened by employing standardized terminology to prioritize monitoring of commonly reported suspected poor-quality medicines for risk-based sampling and testing within the supply chain.

Poor-quality, substandard and falsified, medicines pose a significant public health threat, particularly in low-middle-income countries. A retrospective study was performed on Kenya's Pharmacovigilance Electronic Reporting System (2014–2021) to characterize medicine quality-related complaints and identify associations using disproportionality analysis. A total of 2767 individual case safety reports were identified, categorized into medicines with quality defects (52.1%), suspected therapeutic failure (41.6%), and suspected adverse drug reactions (6.3%). Predominantly reported were antineoplastic agents (28.6%), antivirals (11.7%), and antibacterial agents (10.8%) potentially linked to non-adherence to good manufacturing practices, inappropriate usage and supply chain degradation. Notably, analgesics (8.2%), and medical devices (3.5%) notified had quality defects, predominantly from government health facilities (60.0%). Antineoplastic agents (20.2%) and antivirals (3.7%) were frequently reported from suspected therapeutic failures and suspected adverse drug reactions, respectively, across both private for-profit facilities (26.5%) and not-for-profit facilities (5.4%). Underreporting occurred in unlicensed health facilities (8.1%), due to unawareness and reporting challenges. Pharmacists (46.1%), and pharmaceutical technicians (11.7%) predominantly reported quality defects, while medical doctors (28.0%) reported suspected therapeutic failures. Orally administered generic medicines (76.9%) were commonly reported, with tablets (5.8%) identified as potential sources of suspected adverse drug reactions, while quality defects were notified from oral solutions, suspensions, and syrups (7.0%) and medical devices (3.9%). The COVID-19 pandemic correlated with reduced reporting possibly due to prioritization of health surveillance. This study provides valuable evidence to supporting the use of medicine quality-related complaints for proactive, targeted regulatory control of high-risk medicines on the market. This approach can be strengthened by employing standardized terminology to prioritize monitoring of commonly reported suspected poor-quality medicines for risk-based sampling and testing within the supply chain. [ABSTRACT FROM AUTHOR]

Background: Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils. Methods: Through a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils' use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana's largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints. Results: A total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method. Conclusions: Generating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems. [ABSTRACT FROM AUTHOR]

Real world healthcare data are commonly used in post‐market safety monitoring studies to address potential safety issues related to newly approved medical products. Such studies typically involve repeated evaluations of accumulating safety data with respect to pre‐defined hypotheses, for which the group sequential design provides a rigorous and flexible statistical framework. A major challenge in designing a group sequential safety monitoring study is the uncertainty associated with product uptake, which makes it difficult to specify the final sample size or maximum duration of the study. To deal with this challenge, we propose an information‐based group sequential design which specifies a target amount of information that would produce adequate power for detecting a clinically significant effect size. At each interim analysis, the variance estimate for the treatment effect of interest is used to compute the current information time, and a pre‐specified alpha spending function is used to determine the stopping boundary. The proposed design can be applied to regression models that adjust for potential confounders and/or heterogeneous treatment exposure. Simulation results demonstrate that the proposed design performs reasonably well in realistic settings [ABSTRACT FROM AUTHOR]

Introduction: Esophageal Stents are used to maintain esophageal lumen patency in esophageal strictures caused by intrinsic and/or extrinsic malignancies and the occlusion of concomitant esophageal fistulas. While data on the efficacy and safety of esophageal stents exist, comprehensive evaluation of adverse events is limited. The aim of this study is to investigate the reported adverse events and device failures associated with esophageal self-expandable metal stents (SEMS) using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. Methods: Post-marketing surveillance data for the esophageal SEMSs were analyzed using the FDA's MAUDE database from January 2014 to December 10, 2023. The outcomes of interest were patient-related adverse events and device failures. Statistical analysis was performed using Microsoft Excel 2010 and SPSS. Pooled numbers and percentages were calculated for each adverse event. Continuous variables underwent analysis using a two-tailed student t test, and significance was set to p ≤ 0.05. Results: During the study period, 548 MAUDE reports revealed 873 device failures and 186 patient-related adverse events. The most common device issues were stent activation, positioning, or separation problems (4 n = 403; 46.2%), followed by device detachment or migration (n = 109, 12.5%), and material problems (n = 93, 10.7%). Patient complications included dysphagia/odynophagia (10%), perforation, pain, and bleeding (each 7.6%). The most common device failures in over-the-wire (OTW) stents and through-the-scope (TTS) stents were activation, positioning, or separation problems (TTS: n = 183, 52.6% vs OTW: n = 220, 41.9%). Compared to OTW stents, TTS stents had higher migration and breakage (13.5% vs. 11.8%, p = 0.24), and (9.2% vs. 6.7%, p = 0.08) respectively, while OTW stents had more challenges with stent advancement or removal (5.1% vs. 0.3%, p < 0.001 and 4.6% vs 3.4%, p = 0.19, respectively) and material problems (14.7% vs. 4.6%, p < 0.001). Activation, positioning, and separation problems were the most frequent device failures in fully covered (FC) and partially covered (PC) stents (FC: n = 62, 32.8%, PC: n = 168, 43.5%). FC stents had higher migration rates (20.6% vs 9.8%, p < 0.001), while PC stents exhibited more material problems (17.4% vs. 5.8%, p < 0.001) and difficulties with advancing the stents (6.7% vs. 0%, p < 0.001). Conclusion: Our examination showed a prevalence of reported device complications associated with stent activation, positioning, and separation problems. Dysphagia or odynophagia emerged as the most frequently reported patient complication. Furthermore, our analysis, provides insights into TTS vs. OTW and FC vs. PC esophageal SEMSs, enabling endoscopists and manufacturers to better understand adverse events and potentially optimize device design for future iterations. [ABSTRACT FROM AUTHOR]

Purpose: The study objective is to document value created by real-world evidence from the Abdominal Core Health Quality Collaborative (ACHQC) for regulatory decisions. The ACHQC is a national effort that generates data on hernia repair techniques and devices. Methods: Two retrospective cohort evaluations compared cost and time of ACHQC analyses to traditional postmarket studies. The first analysis was based on 25 reports submitted to the European Medicines Agency of 20 mesh products for post-market surveillance. A second analysis supported label expansion submitted to the Food and Drug Administration, Center for Devices and Radiological Health for a robotic-assisted surgery device to include ventral hernia repair. Estimated costs of counterfactual studies, defined as studies that might have been done if the registry had not been available, were derived from a model described in the literature. Return on investment, percentage of cost savings, and time savings were calculated. Results: 45,010 patients contributed to the two analyses. The cost and time differences between individual 25 ACHQC analyses (41,112 patients) and traditional studies ranged from $1.3 to $2.2 million and from 3 to 4.8 years, both favoring use of the ACHQC. In the second label expansion analysis (3,898 patients), the estimated return on investment ranged from 11 to 461% with time savings of 5.1 years favoring use of the ACHQC. Conclusions: Compared to traditional postmarket studies, use of ACHQC data can result in cost and time savings when used for appropriate regulatory decisions in light of key assumptions. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic duct stents (PDS) are widely used for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, there is a paucity of data regarding the adverse events associated with PDS placement. This study aims to investigate the reported adverse events and device failures related to PDS, utilizing the Manufacturer and User Facility Device Experience (MAUDE) database maintained by the U.S. Food and Drug Administration (FDA). Methods: Post-marketing surveillance data from January 2013 to December 8, 2023, were extracted from the FDA's MAUDE database to analyze the reports pertaining to the use of commonly used PDS. The primary outcomes of interest were device issues and patient-related adverse events. Statistical analysis was performed using Microsoft Excel 2010, with the calculation of pooled numbers and percentages for each device and patient adverse event. Results: A total of 579 device issues and 194 patient-related adverse events were identified. Device issues were primarily attributed to stent deformation (n = 72; 12.4%), followed by migration of the device into the pancreatic duct or expulsion out of the duct (n = 60; 10.4%), and stent fracture/breakage (n = 55; 9.4%). Among the patient-reported adverse events, inflammation was the most common (n = 26; 13.4%), followed by reports of stents becoming embedded in tissue (n = 21; 10.8%) and stent occlusion/obstruction (n = 16; 8.2%). The most prevalent device failures associated with Advanix stents were material deformation, with perforation (n = 3, 30%) being the most frequently reported adverse event. Concerning Geenen stents, migration or expulsion of the device (n = 34, 16.9%) constituted the most common device-related adverse events, while inflammation (n = 20, 16.7%) was the most frequently reported patient-related issue. For Zimmon stents, migration or expulsion of the device (n = 22, 8.8%) were the most frequently reported device-related problems, whereas perforation (n = 7, 10.9%) and bleeding (n = 7, 10.9%) were the most frequent patient-related adverse events. Conclusion: Our findings highlight important device and patient adverse events that endoscopists and referring providers should be aware of before considering pancreatic stent placement. [ABSTRACT FROM AUTHOR]

ABSTRACT Post-market surveillance of test performance is a critical function of public health agencies and clinical researchers that ensures tests maintaining diagnostic characteristics following their regulatory approval. Changes in product quality, manufacturing processes over time, or the evolution of new variants may impact product performance. During the COVID-19 pandemic, a plethora of point-of-care tests (POCTs) was released onto the Canadian market. This study evaluated the performance characteristics of several of the most widely distributed POCTs in Canada, including four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT). All tests were challenged with 149 SARS-CoV-2 clinical positives, including multiple variants up to and including Omicron XBB.1.5, as well as 29 clinical negatives. Results were stratified based on whether the isolate was Omicron or pre-Omicron as well as by reverse transcriptase quantitative PCR Ct value. The test performance of each POCT was consistent with the manufacturers' claims and showed no significant decline in clinical performance against any of the variants tested. These findings provide continued confidence in the results of these POCTs as they continue to be used to support decentralized COVID-19 testing. This work demonstrates the essential role of post-market surveillance in ensuring reliability in diagnostic tools.IMPORTANCEPost-market surveillance of diagnostic test performance is critical to ensure their reliability after regulatory approval. This is especially critical in the context of the COVID-19 pandemic as the use of point-of-care tests (POCTs) became widespread. Our study focused on four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT) that were widely distributed across Canada, assessing their performance using many SARS-CoV-2 variants, including up to Omicron subvariant XBB.1.5. Overall, we found no significant difference in performance against any variant, reinforcing confidence in their use. As concerns in test efficacy have been raised by news outlets, particularly regarding the BTNX Rapid Response, this work is even more timely and crucial. Our research offers insights into the performance of widely used COVID-19 POCTs but also highlights the necessity for post-market surveillance.

The study compares an artificial intelligence technology with traditional manual search of literature databases to assess the accuracy and efficiency of retrieving relevant articles for post-market surveillance of in vitro diagnostic and medical devices under the Medical Device Regulation and In Vitro Diagnostic Medical Device Regulation. Over a 3-year period, literature searches and technical assessment searches were performed manually or using the Huma.AI platform to retrieve relevant articles related to the safety and performance of selected in vitro diagnostic and medical devices. The manual search involved refined keyword searches, screening of titles/abstracts / full text, and extraction of relevant information. The Huma.AI search utilized advanced caching techniques and a natural language processing system to identify relevant reports. Searches were conducted on PubMed and PubMed Central. The number of identified relevant reports, precision rates, and time requirements for each approach were analyzed. The Huma.AI system outperformed the manual search in terms of the number of identified relevant articles in almost all cases. The average precision rates per year were significantly higher and more consistent with the Huma.AI search compared with the manual search. The Huma.AI system also took significantly less time to perform the searches and analyze the outputs than the manual search. The study demonstrated that the Huma.AI platform was more effective and efficient in identifying relevant articles compared with the manual approach. • Post-market surveillance (PMS) is monitoring device safety and performance. • New EU in vitro diagnostic and medical device regulations impact PMS. • Searching the literature for safety signals is time-consuming. • AI assistance reduces human error, and increases search efficiency and precision. • These improvements are crucial for compliance. [ABSTRACT FROM AUTHOR]

Efficacy and safety data for ibrutinib in Japanese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) were limited at the time of its approval in Japan. All-case post-marketing surveillance was conducted in Japanese R/R MCL patients who began ibrutinib treatment between December 2016 and December 2017, and patients were followed until 30 June 2020. In the effectiveness analysis set (n = 202), the overall response rate was 59.9%, 52-week progression-free survival was 47.5%, and overall survival was 69.3%. Safety was assessed in 248 patients (median age 74.0 years). When ibrutinib treatment was started, patients had received a median of three prior lines of therapy. The overall incidence of adverse events (AE) was 74.6%, and AE frequency and severity grade distribution were similar between patients with 1 versus more than 1 prior line of therapy. The most common AE was platelet count decreased (all grades; 10.4%), similarly to previous observations in patients with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma. Five patients (2.0%) developed atrial fibrillation. The effectiveness and safety of ibrutinib were consistent with its known profile at approval in Japan. These results suggest that ibrutinib is effective and safe in Japanese R/R MCL patients in routine clinical practice. [ABSTRACT FROM AUTHOR]

Despite the acceleration in the use of digital health technologies across different aspects of the healthcare system, the full potential of real-world data (RWD) and real-world evidence (RWE) arising from the technologies is not being utilised in decision-making. We examine current national efforts and future opportunities to systematically use RWD and RWE in decision-making in five countries (Estonia, Finland, Germany, Italy and the United Kingdom), and then develop a framework for promotion of the systematic use of RWD and RWE. A review assesses current national efforts, complemented with a three-round consensus-building exercise among an international group of experts (n 1 = 44, n 2 = 24, n 3 = 24) to derive key principles. We find that Estonia and Finland have invested and developed digital health-related policies for several years; Germany and Italy are the more recent arrivals, while the United Kingdom falls somewhere in the middle. Opportunities to promote the systematic use of RWD and RWE were identified for each country. Eight building blocks principles were agreed through consensus, relating to policy scope, institutional role and data collection. Promoting post-market surveillance and digital health technology vigilance ought to rely on clarity in scope and data collection with consensus reached on eight principles to leverage RWD and RWE. [ABSTRACT FROM AUTHOR]

Total hip and knee replacement are effective operations for the management of end-stage arthritis. There are increasing numbers of these operations being performed, and the rate of increase is anticipated to continue into the future (1, 2, 3, 4). There is also a substantial rise in the lifetime risk of a person receiving a total hip or knee replacement and this has been shown in several countries (5, 6, 7, 8). There are a large number of joint replacement prostheses on the market available for use and not all perform the same. Many have no published outcomes. Joint replacement registries provide an appropriate way to monitor the real-world outcomes of these procedures and can provide comparative data on the rates of revision for specific prostheses. Revisions are generally defined in joint registries as a removal or exchange of a prosthesis or part thereof and provide an unambiguous record of a problem with the joint replacement. There are many factors that affect revision rates. Non-device-related issues may include patient factors, surgical technique, surgeon experience and volume of cases. Device-related factors may contribute to the variation in the rates of revision with individual prostheses.

Introduction: The EU Medical Device Regulation 2017/745 defines new rules for the certification and post-market surveillance of medical devices (MD), including an additional review by Expert Panels of clinical evaluation data for high-risk MD if reports and alerts suggest possibly associated increased risks. Within the EU-funded CORE-MD project, our aim was to develop a tool to support such process in which web-accessible safety notices (SN) are automatically retrieved and aggregated based on their specific MD categories and the European Medical Device Nomenclature (EMDN) classification by applying an Entity Resolution (ER) approach to enrich data integrating different sources. The performance of such approach was tested through a pilot study on the Italian data. Methods: Information relevant to 7622 SN from 2009 to 2021 was retrieved from the Italian Ministry of Health website by Web scraping. For incomplete EMDN data (68%), the MD best match was searched within a list of about 1.5 M MD on the Italian market, using Natural Language Processing techniques and pairwise ER. The performance of this approach was tested on the 2440 SN (32%) already provided with the EMDN code as reference standard. Results: The implemented ER method was able to correctly assign the correct manufacturer to the MD in each SN in 99% of the cases. Moreover, the correct EMDN code at level 1 was assigned in 2382 SN (97.62%), at level 2 in 2366 SN (96.97%) and at level 3 in 2329 SN (95.45%). Conclusion: The proposed approach was able to cope with the incompleteness of the publicly available data in the SN. In this way, grouping of SN relevant to a specific MD category/group/type could be used as possible sentinel for increased rates in reported serious incidents in high-risk MD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Monitoring cardiac parameters is the fundamental aspect of every diagnostic process and is facilitated by electrocardiography (ECG) devices. This way, continuous state-of-the-art performance of ECG devices can be ensured. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of ECG devices for post-market surveillance purposes. METHOD: The method was developed on the basis of International Organisation of Legal Metrology (OIML) guidelines and applied in healthcare institutions from 2018 to 2021. RESULTS: The developed method was validated in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of the ECG device as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of ECG devices during PMS, besides increasing reliability of the devices, is the first step in the digital transformation of the management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Defibrillators are medical devices (MDs) used in the most critical situations, hence their performance must be ensured at all times. This requires defibrillators to be subjected to regular performance assessments after they have been placed on the market. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel evidence-based method for conformity assessment testing of defibrillators. METHOD: The proposed method is developed in accordance with the International Organisation of Legal Metrology (OIML) guidelines and is intended to be used for conformity assessment testing of defibrillators for post-market surveillance purposes. RESULTS: The developed method was validated from 2018 to 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of defibrillators as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of defibrillators during PMS, besides increasing reliability of the devices, is the first step in the digital transformation of the management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patient monitors are medical devices used to monitor vital parameters such as heart rate, respiratory rate, blood pressure, blood oxygen saturation, and body temperature during inpatient treatment. As such, patient monitors provide physicians with information necessary to adjust the treatment as well as evaluate the overall status and recovery of the patient. Measurements made by intrinsic sensors of patient monitors must be compliant and provide reliable readings in order to ensure safety and optimal quality of care to the patients. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of patient monitors in healthcare institutions for post-market surveillance purposes. METHOD: The method was developed on the basis of metrology characteristics of sensors used to monitor vital parameters observed by patient monitors and evaluation of their vital safety and performance parameters. In addition to the evaluation of essential safety and visual integrity of patient monitors, their performance in terms of accuracy of the readings is evaluated. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of patient monitors as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of patient monitors during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Premature born infants or infants born sick require immediate medical attention and decreasing the stress imposed onto their body by the environment. Infant incubators provide an enclosed environment that can be controlled to fit the needs of the infant. As such, their performance must be consistent and without significant deviations. The only manner to ensure this is by post-market surveillance (PMS) focused on evaluation of both safety and performance. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of infant incubators for post-market surveillance purposes. METHOD: The method was developed based on guidelines for devices providing measurements laid out by the International Organisation of Legal Metrology (OIML). The methodology was validated during a four year period in healthcare institutions of all levels. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of infant incubators as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of infant incubators during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anaesthesia machines, as moderate to high-risk medical devices intended for use on patients during surgical procedures must be safe and reliable with traceable performance every time they are used in healthcare practice. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel evidence-based method for conformity assessment testing of anaesthesia machines for post-market surveillance purposes. METHOD: The novel method is developed according to the International Organisation of Legal Metrology (OIML) guidelines and is to be used for the purpose of conformity assessment testing of anaesthesia machines with respect to their technical and metrological characteristics during PMS. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of anaesthesia machines as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of anaesthesia machines during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mechanical ventilators are medical devices used in intensive care units when patients are in need of mechanical aid to facilitate the process of breathing. As the function of breathing is the exchange of gases, the mechanical ventilator takes over that function while the patient is incapable to spontaneous breathing. As these devices are used to maintain the life of patents, their performance must be ensured and there cannot be significant deviations in the volumes and pressure of gases they introduce to the patient. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of mechanical ventilators for post-market surveillance purposes. METHOD: The method was developed on the basis of metrology characteristics of mechanical ventilators and evaluation of their vital safety and performance parameters. In addition to the evaluation of essential safety and visual integrity of mechanical ventilators, their performance in terms of volume of oxygen delivered to the patient as well as the flow and pressure of the delivered gas is evaluated. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of mechanical ventilators as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of mechanical ventilators during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dialysis machines are used regularly in healthcare practice. They are classified as a type of medical device with moderate and high risk therefore significant requirements are placed on their safety and performance every time they are used on patients. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel evidence-based method for conformity assessment testing of dialysis machines for post-market surveillance purposes. METHOD: The novel method is developed according to the International Organisation of Legal Metrology (OIML) guidelines and is to be used for the purpose of conformity assessment testing of Dialysis machines with respect to their metrological characteristics during PMS. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of dialysis machines as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of dialysis machines during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Introduction of fluids, medicaments and nutrients into the human body during hospitalization is fundamental for treatment and healing of patients. Fluids are introduced by means of infusion pumps while nutrients and medicaments are introduced by perfusion pumps. It is of vital importance for these devices to deliver exact amounts of the aforementioned substances as significant deviations can result in severe patient harm. Therefore it is important to effectively monitor their performance and prevent failures. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of infusion and perfusion pumps for post-market surveillance purposes. METHOD: The method was developed on the basis of metrology characteristics of the devices. In addition to the evaluation of essential safety and visual integrity of infusion and perfusion pumps, their performance in terms of delivered volumes was assessed and monitored. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of infusion and perfusion pumps as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of infusion and perfusion pumps during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Therapeutic ultrasounds are medical devices used for treatment of conditions such muscle spasms, joint contractures or general muscle pain. Their function relies in the delivery of ultrasonic pulses that generate heat in tissue thus relieving the symptoms of aforementioned conditions. Accuracy of the delivered pulses directly affects the quality and effectiveness of the treatment and has to be ensured throughout the utilization of the therapeutic ultrasound in practice. The new Medical Device Regulation (MDR) defines medical device post-market surveillance (PMS) as performed by independent, third-party, notified bodies more strategically in hope to improve traceability of device performance. However, there is still an apparent gap in terms of standardised conformity assessment testing methods. OBJECTIVE: This paper proposes a novel method for conformity assessment testing of therapeutic ultrasounds for post-market surveillance purposes. METHOD: The method was developed based on metrology characteristics of therapeutic ultrasounds and includes visual, electrical safety and performance inspections of therapeutic ultrasounds to ensure that both safety and treatment reliability are achieved. RESULTS: The developed method was validated between 2018 and 2021 in healthcare institutions of all levels. The results obtained during validation suggest that conformity assessment testing of therapeutic ultrasounds as a method used during PMS contributes to significant improvement in devices' accuracy and reliability. CONCLUSION: A standardized approach in conformity assessment testing of therapeutic ultrasounds during PMS, besides increasing reliability of the devices, is the first step in digital transformation of management of these devices in healthcare institutions opening possibility for use of artificial intelligence. [ABSTRACT FROM AUTHOR]

With the advancement of Artificial Intelligence (AI), clinical engineering has witnessed transformative opportunities, enabling predictive maintenance of medical devices, optimization of healthcare workflows, and personalized patient care. Respiratory equipment plays a vital role in modern healthcare, supporting patients with compromised or impaired respiratory capacities. However, ensuring the reliability and safety of these devices is crucial to prevent adverse events and ensure patient well-being.This study aims to explore machine learning techniques to enhance predictive maintenance for mechanical ventilators.The dataset used for this study contains information about 1350 entries of mechanical ventilators, made by 15 different manufacturers and available in 30 distinct models. Different machine learning algorithms, including Logistic Regression, Decision Trees, Random Forest, K-nearest Neighbors, Support Vector Machines, Naive Bayes, and XG Boost are developed and tested in terms of their performance in predicting mechanical ventilator failures.The ensemble methods, particularly Random Forest and XGBoost, have proven to be more adept at handling the complexities of the dataset. The Decision Tree and Random Forest models both showed remarkable accuracies of approximately 0.993, while K-Nearest Neighbors (KNN) performed exceptionally with near perfect accuracy.Adoption of automated systems based on artificial intelligence will help in overcoming challenges of ensuring quality of MDs that are already being used in healthcare institutions. Implementing machine learning-based predictive maintenance can significantly enhance the reliability of mechanical ventilators in healthcare settings. [ABSTRACT FROM AUTHOR]

Poorly regulated and insufficiently maintained medical devices (MDs) carry high risk on safety and performance parameters impacting the clinical effectiveness and efficiency of patient diagnosis and treatment. After the MD directive (MDD) had been in force for 25 years, in 2017 the new MD Regulation (MDR) was introduced. One of the more stringent requirement is a need for better control of MD safety and performance post-market surveillance mechanisms.To address this, we have developed an automated system for management of MDs, based on their safety and performance measurement parameters, that use machine learning algorithm as a core of its functioning.In total, 1997 samples were collected during the inspection process of defibrillator inspections performed by an ISO 17020 accredited laboratory at various healthcare institutions in Bosnia and Herzegovina. This paper presents solution developed for defibrillators, but proposed system is scalable to any other type of MDs, both diagnostic and therapeutic.Various machine learning algorithms were considered, including Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB) and Logistic Regression (LR). In addition, random forest regressor and XG Boost algorithms were tested for their predictive capabilities in the field of defibrillator output error prediction. These algorithms were selected because of their ability to handle large datasets and their potential for achieving high prediction accuracy. The highest accuracy achieved on this dataset was 94.8% using the Naive Bayes algorithm. The XGBoost Regressor with its r2 of 0.99 emerged as a powerful tool, showcasing exceptional predictive accuracy and the ability to capture a substantial portion of the dataset's variability.The results of this study demonstrate that clinical engineering (CE) and health technology management (HTM) departments in healthcare institutions can benefit from proposed automatization of defibrillator maintenance scheduling in terms of increased safety and treatment of patients, on one side, and cost optimization in MD management departments, on the other side. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medical devices (MDs) represent the backbone of the modern healthcare system. Considering their importance in daily medical practice, the process of manufacturing, marketing and usage has to be regulated at all levels. Harmonized evidence-based conformity assessment of MDs during PMS relying on traceability of medical device measurements can contribute to higher reliability of MD performance and consequently to higher reliability of diagnosis and treatments. OBJECTIVE: This paper discusses issues within MD post-market surveillance (PMS) mechanisms in order to set a path to harmonization of MD PMS. METHODS: Medline (1980-2021), EBSCO (1991-2021), and PubMed (1980-2021) as well as national and international legislation and standard databases along with reference lists of eligible articles and guidelines of relevant regulatory authorities such as the European Commission and the Food and Drug Administration were searched for relevant information. Journal articles that contain information regarding PMS methodologies concerning stand-alone medical devices and relevant national and international legislation, standards and guidelines concerning the topic were included in the review. RESULTS: The search strategy resulted in 2282 papers. Out of those only 24 articles satisfied the eligibility criteria and were finally included in the review. Papers were grouped per categories: medical device registry, medical device adverse event reporting, and medical device performance evaluation. In addition to journal articles, national and international legislation, standards, and guidelines were reviewed to assess the state of PMS in different regions of the world. CONCLUSION: Although the regulatory framework prescribes PMS of medical devices, the process itself is not harmonized with international standards. Particularly, conformity assessment of MDs, as an important part of PMS, is not measured and managed in a traceable, evidence-based manner. The lack of harmonization within PMS results in an environment of increased adverse events involving MDs and overall mistrust in medical device diagnosis and treatment results. [ABSTRACT FROM AUTHOR]

Purpose: Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients.Methods: In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients.Results: A total of 654 patients (51.73 ± 15.12 years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6 mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment.Conclusion: The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens.Trial Registration: Clinicaltrials.gov identifier: NCT04460079. [ABSTRACT FROM AUTHOR]

The recent passage of European Union (EU) Regulation 2017/745 on medical devices (MDs) has improved the classification of MDs and revised their approval process and the post-marketing evaluation of their safety and effectiveness, promoting transparency and post-marketing oversight in Europe. This new regulation can better ensure patient safety and provide new opportunities for therapeutic innovation. In addition, the new regulations include and define MDs made of substances or of combinations of substances (substance-based MDs: SBMDs). The impressive growth of the MD, including SBMDs, that have been marketed over the recent years has likely been a relevant factor fueling this change. MD regulation requires a major effort from both industry and regulatory bodies to comply with its provisions. Manufacturers should produce sufficient clinical evidence that an MD, under normal conditions of use, provides adequate performance and that the foreseeable risks and frequency of adverse events (AEs) have an acceptable minimum rate, taking into account the benefits provided. We describe how we implemented the post-marketing surveillance (PMS) system of SBMDs to properly deal with post-market monitoring and confirmation of safety and performance, including AEs and the benefit–risk evaluation, as required by the 2017/745 Regulation. The two pillars of this novel system are: 1) passive vigilance, i.e., spontaneous reporting and 2) active post-marketing clinical follow-up (PMCF) activities, which systematically gather, record, and analyze real-world data (RWD) on performance, quality, function, use, tolerability, and safety of an MD, collected through a dedicated, structured web platform. Active PMCF is achieved through a process of generation, validation, and administration of digital questionnaires to all stakeholders, i.e., patients, physicians, both general practitioners and specialists, and pharmacists. The technology, potential use, advantages, and limitations of this large source of RWD are also discussed.

Both Artificial Intelligence ('AI') and genome editing are technologies that on their own promise to revolutionise healthcare. But their common application can facilitate progress in the field even more. Multiplied benefits go along with increased risks. In this article, I identify and analyse legal challenges associated with applying AI facilities in medicinal products based on somatic genome editing. These challenges are caused by several factors. First, the two technologies share the characteristics that create and facilitate common risks. Second, each of the technologies is subject to very complex regulatory frameworks. These frameworks are not substantially connected to control the safety and quality of the common product. The main argument of this paper is that the management of common risks is only possible through common procedures. I discover the gaps in the current legislation that prevent from establishing these common procedures and provide recommendations to fill them in. [ABSTRACT FROM AUTHOR]

Background: Monitoring for substandard medicines by regulatory agencies is a key post‐market surveillance activity. It is important to prioritise critical product defects for review to ensure that prompt risk mitigation actions are taken. Methods: A regulatory risk impact prioritisation model for product defects (RISMED) with 11 factors considering the seriousness and extent of impact of a defect was developed. The model generated an overall score that categorised cases into high, medium or low impact. The model was further developed into a statistical risk scoring model (stat‐RISMED) using multivariate logistic regression that classified cases into high and non‐high impact. Both models were evaluated against an expert‐derived gold standard annotation corpus and tested on an independent dataset. Results: Product defect cases received from January 2011 to June 2020 (n = 660) were used to train stat‐RISMED and cases from July 2020 to June 2021 (n = 220) for validation. The stat‐RISMED identified four factors associated with high impact cases, namely defect classification based on MedDRA‐HSA terms, therapeutic indication of product, detectability of defect and whether any overseas regulatory actions were performed. Compared to RISMED, stat‐RISMED achieved an improved sensitivity (94% vs 42%) and positive predictive value (47% vs 43%) for the identification of high impact cases, against the gold standard labels. Conclusions: This study reported characteristics that predicts cases with high impact, and the use of a statistical model to identify such cases. The model may potentially be applied to prioritise product defect issues and strengthen overall surveillance efforts of substandard medicines. [ABSTRACT FROM AUTHOR]

Over the last several years, the recommended use of the live-attenuated influenza vaccine (LAIV) for children has evolved in the United States (US) in response to evidence of a potential decrease in LAIV effectiveness based on post-market monitoring. These issues were not observed in Canada or elsewhere; consequently, recommendations from Canada’s National Advisory Committee on Immunization (NACI) and the US Advisory Committee on Immunization Practices (ACIP) on whether to use LAIV differed for two influenza seasons (2016–2017 and 2017–2018). This retrospective describes how NACI arrived at its recommendations in response to post-market signals of reduced LAIV performance from the US in 2013–2014 and again in 2015–2016. NACI’s experience with LAIV marks the first time in Canada where a preferential recommendation on the use of an influenza vaccine in a routine immunization program was reversed. This experience highlights the importance of ongoing post-market monitoring of vaccines, international collaboration and careful consideration of local context to inform vaccine recommendations. NACI’s capacity for timely responses to post-market vaccine performance signals will facilitate responsiveness to similar post-market monitoring signals from the coronavirus disease 2019 (COVID-19) vaccines.

Josep Pane,1,2 Katia MC Verhamme,1 Dorian Villegas,2 Laura Gamez,3 Irene Rebollo,3 Miriam CJM Sturkenboom4 1Department of Medical Informatics, Erasmus Medical Center, University of Rotterdam, Rotterdam, Netherlands; 2Alcon, Fort Worth, USA; 3Novartis, Barcelona, Spain; 4Julius Global Health, University Medical Center Utrecht, Utrecht, NetherlandsCorrespondence: Josep PaneDepartment of Medical Informatics, Erasmus Medical Center, University of Rotterdam, Rotterdam, 3000, CA, NetherlandsEmail jpanesalvado@gmail.comBackground: Previous safety issues involving medical devices have stressed the need for better safety signal detection. Various European Union (EU) national competent authorities have started to focus on strengthening the analysis of vigilance data. Consequently, article 90 of the new EU regulation states that the European Commission shall put in place systems and processes to actively monitor medical device safety signals.Methods: A systematic literature review was conducted to synthesize the current state of knowledge and investigate the present tools used for medical device safety signal detection. An electronic literature search was performed in Embase, Medline, Cochrane, Web of science, and Google scholar from inception until January 2017. Articles that included terms related to medical devices and terms associated with safety were selected. A further selection was based on the abstract review. A full review of the remaining articles was conducted to decide on which articles finally to consider relevant for this review. Completeness was assessed based on the content of the articles.Results: Our search resulted in a total of 20,819 articles, of which 24 met the inclusion criteria and were subject to data extraction and completeness scoring. A wide range of data sources, especially spontaneous reporting systems and registries, used for the detection and assessment of product problems and patient harms associated with the use of medical devices, were studied. Coding is remarkably heterogeneous, no agreement on the preferred methods for signal detection exists, and no gold standard for signal detection has been established thus far.Conclusion: Data source harmonization, the development of gold standard signal detection methodologies and the standardization of coding dictionaries are amongst the recommendations to support the implementation of a new proactive approach to signal detection. The new safety surveillance system will be able to use real-world evidence to support regulatory decision-making across all jurisdictions.Keywords: signal detection, safety surveillance, post-market surveillance, post-market data sources, coding dictionaries, medical devices

Background: The oral cavity harbors many microbes that may cause diseases, including dental caries and periodontal diseases. Progressive inflammation from periodontal diseases may lead to gum detachment from the teeth. Povidone-iodine and chlorhexidine mouth rinses and gargles are broad-spectrum antimicrobial products that effectively manage dental caries and periodontal diseases and eliminate plaques. This study was conducted in Nairobi County, Kenya to establish the quality of povidone-iodine and chlorhexidine oral care products by determining the content of the active pharmaceutical ingredient and compliance with labeling requirements. Methods: A total of 34 samples (from 15 brands) of povidone-iodine and 15 samples (from nine brands) of chlorhexidine were collected from retail pharmacies using convenience sampling. All samples were subjected to labeling analysis, identity, and assay tests. Potentiometric titration was used to assay povidone-iodine in the samples, while chlorhexidine was assayed using high-performance liquid chromatography (HPLC) according to British Pharmacopeia 2017 specifications. Results: All samples complied with identification tests. Moreover, 47.1% of povidone-iodine and 66.7% of chlorhexidine products complied with pharmacopoeial assay specifications. Five povidone-iodine (14.7%) and four chlorhexidine (26.7%) samples had missing label information on the storage conditions and the address of the manufacturer. Conclusions: Strict adherence to current Good Manufacturing Practices (cGMP) by manufacturers of povidone-iodine and chlorhexidine mouthwashes/gargles is necessary to guarantee quality assured products in the market. Regular post-market surveillance and regulatory enforcement of standards are instrumental in minimizing the circulation of poor-quality products.

Abstract Background The production and use of malaria rapid diagnostic tests (RDTs) has risen dramatically over the past 20 years. In view of weak or non-existing in vitro diagnostics (IVD) regulations and post-marketing surveillance (PMS) systems in malaria endemic countries, the World Health Organization, later joined by the Foundation for Innovative New Diagnostics, established an independent, centralized performance evaluation and Lot Testing (LT) programme to safeguard against poor quality of RDTs being distributed through the public health sector of malaria endemic countries. RDT performances and manufacturer quality management systems have evolved over the past decade raising questions about the future need for a centralized LT programme. Results Between 2007 and 2017, 6056 lots have been evaluated, representing approximately 1.6 Billion RDTs. A total of 69 lots (1.1%) failed the quality control. Of these failures, 26 were detected at receipt of the RDT lot in the LT laboratory, representing an estimated 7.9 million poor quality RDTs, and LT requesters were advised that RDTs were not of sufficient quality for use in patient management. Forty-three were detected after long-term storage in the laboratory, of which 24 (56%) were found to be due to a major issue with insufficient buffer volume in single use buffer vials, others predominantly showing loss of sensitivity. The annual cost of running the programme, based on expenses recorded in years 2014–2016, an estimated volume of 700 lots per year and including replenishment of quality control samples, was estimated at US$ 178,500 ($US 255 per lot tested). Conclusions Despite the clear benefits of the centralized LT programme and its low cost compared with the potential costs of each country establishing its own PMS system for RDTs, funding concerns have made its future beyond 2020 uncertain. In order to manage the risks of misdiagnosis due to low quality RDTs, and to ensure the continued safety and reliability of malaria case management, there is a need to ensure that an effective and implementable approach to RDT quality control continues to be available to programmes in endemic countries.

Abstract Background For novel tobacco products that potentially reduce the risk of tobacco harm, post-market surveillance is important to observe population usage and behaviours associated with everyday use. This pilot study was performed to examine the use of tobacco products in three Japanese urban regions. Methods This study was a cross-sectional epidemiological survey administered in Sendai, Tokyo and Osaka, Japan, from May 19th to June 25th, 2018. Participants were selected with a three-stage probability random sampling process that first identified primary sampling units, then households and finally individuals. Eligible participants were aged at least 20 years who were willing to participate after information about the study was provided. People younger than 20 years and those living in institutions were excluded. Questionnaires were paper based and administered door to door. Results Responses were obtained from 4154 participants. Sixty-five percent self-reported being never, 19% current and 16% former users of any tobacco product at the time of the survey. Combustible tobacco products (almost all being cigarette) were used most (16%) followed by HTPs (5%). In the categories of combustible tobacco users and HTP users, 70% and 16%, respectively, used these products exclusively. Dual use was reported by 11% of respondents. Compared with 12 months before the survey, 12% of sole combustible tobacco products users were using HTPs exclusively or as dual users and 6% had quit tobacco products completely; 94% of sole HTP users remained sole users and 4% had quit tobacco products completely; and amongst dual users 12% had reverted to exclusive use of combustible tobacco products, 14% had switched to sole use of HTPs and 4% had quit tobacco products completely. Conclusion HTPs seem to be accepted as an alternative tobacco product amongst combustible tobacco users. Given complex findings for dual use, improved understanding of the motivations underlying this behaviour would be of interest.

Background: Good Manufacturing Practices (GMP) is the bedrock of quality assurance in the pharmaceutical industry that ensures that products are consistently produced and controlled according to quality standards. This study compared the GMP conformance of pharmaceutical facilities across two fiscal years, 2018/2019 and 2019/2020, using the East African GMP Compendium on Good Manufacturing Practices, 2014, as a benchmark., Methods: We analyzed the proportion of conformance of foreign pharmaceutical industries to GMP standards and reported the aggregated data over a two-year period., Results: Inspected facilities had notable non-conformances, most commonly related to laboratory quality control and premises. We noted a downward trend in conformance in 2019/2020 compared with 2018/2019, with only 32.9% of facilities adhering to EAC GMP requirements, down from 50% in the previous year. The COVID-19 pandemic has affected the ability to conduct on-site inspections, and may have contributed to the lower conformance rate., Conclusions: These findings underscore the crucial need to continue GMP inspections and the importance of taking corrective actions to ensure adherence to the quality standards for products marketed in Tanzania. The study further revealed the significance of desk reviews in assisting regulatory authorities in facing unforeseen challenges such as pandemics., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To compare relative risk (RR) of central line-associated bloodstream infection (CLABSI) between hospitals using Clave needleless connector technologies (NCT) and comparator hospitals using non-Clave NCT. And, to estimate avoided CLABSIs, mortality, and cost savings., Background: Needleless connectors, while protective against needlestick injury, have long been implicated as a potential risk for CLABSI. Significant RR reduction of CLABSI among the many NCT has not been clinically demonstrated., Methods: The U.S. Healthcare-Associated Infections database was accessed for CLABSI data for calendar year 2019 via the Centers for Medicare and Medicaid Services website. This dataset was merged with the Clave NCT manufacturer's 2019 database to identify hospitals purchasing Clave NCT (MicroClave™, NanoClave™, Clave Neutron™, Clave™, Microclave™ Clear) and non-Clave NCT comparator hospitals. Sub-analysis of Clave NCT hospitals included: (1) Clave NCT mixed-use and (2) Clave high-volume use hospitals. The standardized infection ratio (SIR) was generated to estimate CLABSI RR after adjusting for intern/resident-to-bed-ratio (IRB), care location, and hospital demographics. Using the RR, avoided CLABSIs, mortality, and cost savings were calculated., Results: A total of 2987 eligible hospitals (1288 Clave NCT, 1699 non-Clave NCT) with 17,452,575 central line-days were evaluated. All three Clave NCT hospital groups showed a statistically significant reduction in RR compared to the non-Clave NCT hospitals. The RR in Clave NCT hospitals was 0.93, a 7% decrease in CLABSI risk ( p  = 0.02). In the Clave NCT subgroups, mixed-use hospitals RR was 0.93, a 7% reduction ( p  = 0.04), while the Clave NCT high-volume hospitals experienced a 19% reduction, RR 0.81 ( p  = 0.04). An estimated 563 CLABSIs and 84 related deaths were avoided with use of Clave NCT and $27,095,231 in cost savings., Conclusion: The use of the Clave NCT, in and of itself, is an effective risk reduction strategy for CLABSI prevention, reduced mortality, and substantial cost savings., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author JB is an employee of ICU Medical. Author MR has received consultancy fees from ICU Medical.

Post-market surveillance of test performance is a critical function of public health agencies and clinical researchers that ensures tests maintaining diagnostic characteristics following their regulatory approval. Changes in product quality, manufacturing processes over time, or the evolution of new variants may impact product performance. During the COVID-19 pandemic, a plethora of point-of-care tests (POCTs) was released onto the Canadian market. This study evaluated the performance characteristics of several of the most widely distributed POCTs in Canada, including four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT). All tests were challenged with 149 SARS-CoV-2 clinical positives, including multiple variants up to and including Omicron XBB.1.5, as well as 29 clinical negatives. Results were stratified based on whether the isolate was Omicron or pre-Omicron as well as by reverse transcriptase quantitative PCR Ct value. The test performance of each POCT was consistent with the manufacturers' claims and showed no significant decline in clinical performance against any of the variants tested. These findings provide continued confidence in the results of these POCTs as they continue to be used to support decentralized COVID-19 testing. This work demonstrates the essential role of post-market surveillance in ensuring reliability in diagnostic tools.IMPORTANCEPost-market surveillance of diagnostic test performance is critical to ensure their reliability after regulatory approval. This is especially critical in the context of the COVID-19 pandemic as the use of point-of-care tests (POCTs) became widespread. Our study focused on four rapid antigen tests (Abbott Panbio, BTNX Rapid Response, SD Biosensor, and Quidel QuickVue) and two molecular tests (Abbott ID NOW and Lucira Check IT) that were widely distributed across Canada, assessing their performance using many SARS-CoV-2 variants, including up to Omicron subvariant XBB.1.5. Overall, we found no significant difference in performance against any variant, reinforcing confidence in their use. As concerns in test efficacy have been raised by news outlets, particularly regarding the BTNX Rapid Response, this work is even more timely and crucial. Our research offers insights into the performance of widely used COVID-19 POCTs but also highlights the necessity for post-market surveillance., Competing Interests: The authors declare no conflict of interest.

• How to select QC rules and frequency based on σ metric. • The requirements of EQA. • How EQA and QC can be integrated. • Processes to deal with failed QC or EQA. • What future laboratory activities will become EQA programs. Effective management of clinical laboratories relies upon an understanding of Quality Control and External Quality Assurance principles. These processes, when applied effectively, reduce patient risk and drive quality improvement. In this Review, we will describe the purpose of QC and EQA and their role in identifying analytical and process error. The two concepts are linked, and we will illustrate that linkage. Some EQA providers offer far more than analytical surveillance. They facilitate training and education and extend quality improvement and identify areas where there is potential for patient harm into the pre-and post-analytical phases of the total testing process. [ABSTRACT FROM AUTHOR]

Abstract Background The vigilant observation of medical devices during post-market surveillance (PMS) for identifying safety-relevant incidents is a non-trivial task. A wide range of sources has to be monitored in order to integrate all accessible data about the safety and performance of a medical device. PMS needs to be supported by an efficient search strategy and the possibility to create complex search queries by domain experts. Results We use ontologies to support the specification of search queries and the preparation of the document corpus, which contains all relevant documents. In this paper, we present (1) the Search Ontology (SON) v2.0, (2) an Excel template for specifying search queries, and (3) the Search Ontology Generator (SONG), which generates complex queries out of the Excel template. Based on our approach, a service-oriented architecture was designed, which supports and assists domain experts during PMS. Comprehensive testing confirmed the correct execution of all SONG functions. The applicability of our method and of the developed tools was evaluated by domain experts. The test persons concordantly rated our solution after a short period of training as highly user-friendly, intuitive and well applicable for supporting PMS. Conclusions The Search Ontology is a promising domain-independent approach to specify complex search queries. Our solution allows advanced searches for relevant documents in different domains using suitable domain ontologies.

Post market examination is to safeguard end users through the close watch of IVDs offered for sale or distribution in the country. Through this action product owner must aware of the problems arises with the IVD in use and analysis the risk associated with the problem reported and take appropriate action to avoid repetition and ensure quality of the IVDs in the market. Rigorous pre-market assessment of IVDs is done by the regulatory authorities; however, there is no enough system and guidance in place for the monitoring of the post-marketing phase of IVDs in most countries including India. This article has been prepared to facilitate and strengthen the reporting of Events attributable to in-vitro diagnostic medical devices in India, harmonized with WHO, National and International best practices. This article suggested the various stakeholders follow this guidance involved in the post market phase of IVDs relates to monitoring of adverse events, reporting of adverse events, reporting timeline, examination of the complaint to determine source, and the subsequent suitable action. This article also aims to create awareness among users about the importance of reporting adverse events relating to the IVDs in India. In order to monitor the quality of the IVDs available in the country and encourage the reporting, this article also urges the central government to make online portal under respective authorities for mandatory reporting, report suspected counterfeit IVDs, for voluntary reporting serious adverse event, product quality problem, product use/medication error, or/failure that is associated with the use of an IVDs. [ABSTRACT FROM AUTHOR]

We aimed to determine the reporting trends and characteristics of Individual Case Safety Reports (ICSRs) from the Zimbabwean national pharmacovigilance system. ICSRs submitted to VigiBaseTM, the World Health Organisation's ICSR database between January 1993 and December 2017 were retrospectively reviewed with respect to the suspected medicine, System Organ Class (SOC), adverse drug reaction (ADR) type and seriousness, Anatomic Therapeutic Chemical (ATC) group, age, and gender. In total, 4071 ICSRs were submitted to VigiBaseTM from targeted spontaneous reporting (n = 2909; 71.5%), vaccine surveillance (n = 679; 16.7%), and passive spontaneous reporting (n = 483; 11.9%), respectively. The median age, ICSR completeness score and timeliness of reporting were 34.0 years (IQR: 14.0; 43.0), 0.90 (IQR: 0.70; 1.00), and 548.0 days (IQR: 266:1131), respectively. More than half of the ICRS were from female patients (n = 2233; 54.9%). Antiretrovirals, antibiotics, vaccines, and anti-tubercular medicines were reported in 62.9%, 27.9%, 16.7%, and 13.3% of submitted ICSRs, respectively. The most frequent ADRs involved the skin and subcutaneous systems (n = 1111; 20.5%), nervous system (n = 733; 13.5%), and gastrointestinal disorders system (n = 654; 12.1%). The number of ADRs reported for each patient was significantly related to the reported medicine's ATC category (P = .001. The number of ADRs was significantly related to the use of antiretroviral agents. In conclusion, Zimbabwe has made significant progress in establishing a functional pharmacovigilance system. However, the present system reports on a limited therapeutic spectrum of medicines and potentially underestimates the national ADR burden. Further work is required to strengthen the more sustainable spontaneous reporting system which potentially captures a variety of therapeutic classes. [ABSTRACT FROM AUTHOR]