Materiovigilance in Perspective: Understanding Its Concept and Practice in the Global Healthcare System

Materiovigilance (Mv) has the same purpose and approach in ensuring patient safety as pharmacovigilance but deals with medical devices associated with adverse events (MDAEs) and their monitoring. Mv has been instrumental in recalling many defective or malfunctioning devices based on their safety data. All MDAEs, such as critical or non-critical, known, or unknown, those with inadequate or incomplete specifications, and frequent or rare events should be reported and evaluated. Mv helps to improve medical devices’ design and efficiency profile and avoid device-related complications and associated failures. It alerts consumers and health professionals regarding counterfeit or substandard devices. Common events reported through Mv are device breakage and malfunction, entry- and exit-site infections, organ perforations or injuries, need for surgery and even death, and life cycle assessment of devices. Health authorities globally have developed reporting frameworks with timeframes for MDAEs, such as MedWatch in the USA, MedSafe in New Zealand, and others. Health professionals and consumers need to be made aware of the significance of Mv in ensuring the safe use of medical devices and getting familiar with the reporting procedures and action plans in case of a device-induced adverse event.


Introduction
Technological advances have significantly influenced healthcare practices, resulting in improved healthcare outcomes. Many technological advancements in recent times, such as drug device-combined modalities, automation and robotics, sophisticated devices, and others, caused a rapid upsurge in the applications of medical devices in healthcare facilities (HCFs) [1]. Medical devices are widely used to diagnose, prevent, and treat different diseases [2] and range from simple meter dose inhalers to complicated operation theater and radiology devices. The global demand for medical devices has risen exponentially and reached 380 billion USD in 2016 from 260 billion USD in 2006, with the burgeoning incidence of stroke, obesity, diabetes, cancer, and many other chronic diseases [1,3]. Hence, with each new product being launched into the market, practitioners, policymakers, regulators, and patients must become aware of their safety, effectiveness, quality assurance, and other essential parameters, which long-term pharmacovigilance (Pv) activities can explore. A similar concept and approach of Pv have been incorporated in medical devices, termed materiovigilance (Mv).
While the use of medical devices is increasing, the concerns regarding their safety are also rising. Like medicines, the post-marketing data of the applications and effects of medical devices on healthcare are also vital sources of evidence to ensure their safety and performance characteristics [4]. It is usual to report adverse events during phases mandatorily I to III of clinical trials and only voluntarily during post-marketing periods (i.e., phase IV clinical trials), but under-reporting is still common during the post-marketing stage [5]. Moreover, as all adverse events cannot be reported during the product development and launch phase due to several inherent limitations of clinical trials, practitioners and regulators must rely on long-term spontaneous reporting by health professionals and patients [6]. Many device manufacturing industries have also started the concept of living data mining techniques to make the regulatory authorities sure that no new device-induced signals arise as with the device use [5].

Pharmacovigilance and Emergence of Materiovigilance
Pharmacovigilance (Pv) is a science dealing with the continuous identification, assessment, evaluation, and prevention of acute and chronic adverse reactions caused by newly launched and already marketed medicines [5][6][7][8][9][10]. Pv these days also covers drug therapy-related problems (DTRPs) shown by herbals, traditional, complementary, and alternative medicines (TCAMs), biologicals and blood products, medical devices, and vaccines [6,11,12]. Pharmacoepidemiologic studies are popular these days to evaluate the safety and effectiveness of medicines in clinical practice [13]. Materiovigilance (Mv) has similar reporting purposes and approaches as that of Pv but deals with adverse reactions caused by medical devices and their prevention strategies [2-4, 8, 14, 15]. For example, devices may lead to adverse events due to their design or manufacturing problems, inadequate maintenance, irrational storage and logistics, poor user instructions or training leading to incorrect use, off-label or unapproved use, and many other context-specific issues [16]. Thus, like all medicines, all medical devices may also have certain risks. Therefore, monitoring the safety of these devices helps withdraw dangerous or potentially dangerous devices from the market and eliminate defects to improve their quality and performance standards [8,15].

Global Materiovigilance Initiatives
The International Medical Device Regulators Forum (IMDRF), comprising 10 countries, such as the USA, Japan, EU, China, South Korea, and India, was set up in 2011 to introduce the concept and implementation of the Mv program to monitor medical devices associated adverse events (MDAEs) and to harmonize international medical device regulation via Mv [8]. The materiovigilance program of India (MvPI), launched on July 6, 2015, helps to systematically collect safety data on device use from Indian population, to monitor MDAEs, to raise awareness among health professionals on their reporting, to monitor benefits versus risks, to generate evidence-based suggestions on safety, and to communicate findings to the stakeholders and regulatory authorities [2,14,15,17]. Table 1 shows Mv initiatives in some countries.

Significance of Materiovigilance
Mv emerged as a modified novel branch of Pv to improve patients' health and safety by reducing the incidence of MDAEs, developing a framework and mechanism for nationwide patient safety monitoring, generating evidencebased data related to medical devices' safety, analyzing their risk-benefit ratio, and disseminating the information to the stakeholders. Mv also assists the regulatory authorities in making decisions related to medical devices, such as collaborating with national and international agencies on MDAEs reporting and investigation to prevent potential adverse events in future. It helps practitioners diagnose, monitor, manage, or mitigate disease or injury. In addition, Mv allows manufacturers to improve design and efficiency profiles of medical devices [1-3, 14, 18] and to perform life cycle assessments of devices and report adverse events to avoid complications of counterfeit or substandard devices, such as device breakage and malfunction, entry-and exit-site infections, organ perforations or injuries, need for surgery, and even death [19].

Search Strategy
Four electronic databases (i.e., PubMed/MEDLINE, Scopus, Science Direct) were searched for medical devices-related studies published in English until October 31, 2022. The following search strategies were used to explore and extract relevant articles: • "Materiovigilance" OR "Pharmacovigilance" OR "Adverse event* report*" OR "Adverse effect* report*" OR "Adverse outcom* report*" AND (Global healthcare" OR "Global healthcare system") • "Medical devices" OR "Medical devices associated adverse events" OR "Medical device recall" AND ("Regulation" OR "Reporting guidelines")

Data Synthesis and Analysis
Information related to materiovigilance was extracted from research articles and review papers and interpreted as tabular forms and figures.

Safety Specifications to be Considered During Materiovigilance Execution
The safety specifications related to devices can be divided into three risk categories like in case of medicines-identified risks (i.e., prominent and relevant evidence-based adverse events), potential risks (i.e., prominent or suspicious adverse events but without sufficient clinical data), and missing information (i.e., critical for estimating postmarketing safety but not available during risk management plan (RMP) phase) [20]. Some risks caused by devices may be life-threatening to patients, users, and even health professionals due to their interactions with other substances, contraindications, malfunctions, falsifications, technical defects, and compromised efficacy [14]. Hence, the USA, European Union, Japan, and Canada agreed upon the joint medical device regulatory landscape to ensure that safe, effective, and innovative devices are used in health care like in diabetes care in these countries [21].

Medical Devices Associated Adverse Events Reporting
Important concerns to be addressed in the case of devices are the global consistency in their classification and approval processes, if not possible, at least transparency [22]. All MDAEs such as critical or non-critical, known or unknown, those related to inadequate or incomplete specifications, and frequent or rare events should be reported [5,14,15] and evaluated case by case and on an aggregate level [5]. The descriptions of devices and their hazards or suspected risks with previous usage experience can also be reported [15]. Table 2 depicts the information required for the reporting of MDAEs. The adverse events reporting system serves as an essential tool whereby all types of MDAEs can be reported to protect users from unforeseen or unexpected effects and to improve their health and safety. The Global Harmonization Task Force (GHTF) provides the manufacturers' guidance in reporting MDAEs and information on handling the same and in deciding whether an event is reportable. In the USA, the FDA requires that manufacturers and importers report serious adverse events (SAEs) or malfunctions of medical devices [14].

Reporting of Medical Devices Associated Adverse Events in Some Countries
The FDA requires that MDAEs must be reported by their manufacturers and importers, including quality problems, defects, and performance errors. Similarly, patients, users, and health professionals can voluntarily report the same in case of treatment failures to improve patient safety [21]. Similarly, manufacturers report the MDAEs to the National Competent Authority (NCA) in Europe within two days, death reports and other deteriorating health problems within ten days, and other non-serious incidents within 30 days. In contrast, health professionals report these to the NCA and the manufacturers [23]. Health Canada reviews applications of new and remodeled or redesigned devices in Canada and requires that deformities be reported by the manufacturers and the consumers on their respective forms, depending on the device category. A potential death case should be Investigation or action taken, root cause analysis (RCA) of problem, challenge, and dechallengerelated information Manufacturer's investigation and action taken Devise risk analysis report, corrective/preventive action taken, device history review reported to Health Canada within ten days, whereas a noncritical case should be within 30 days [24].
Manufacturers and sponsors report per the guidelines set by the Therapeutic Goods Act (TGA) in Australia, and TGA maintains records containing a detailed history of all lots, components, and potential health hazards for a maximum of five years [25]. The MDAEs are reported by the marketing authorization holder (MAH) within two weeks, and any death events or critical cases are reported within 30 days in Japan [26]. Likewise, China Food and Drug Administration (CFDA)'s National Center for ADR Monitoring collects adverse event reports and manages post-approval surveillance in China, even at regional and provincial levels. Injury-related events should be reported to the local ADR monitoring centers within 15 days and death events to the National Center. However, manufacturers and distributors can also directly submit the reports to the National Center in the country [27]. In India, health professionals, manufacturers or importers, and consumers can voluntarily report MDAEs to date. However, manufacturers and importers should mandatorily report any serious events to the Central Drugs Standard Control Organization (CDSCO), which then takes the necessary regulatory decisions on the safety of devices as per the established procedures of MvPI [3,17]. Figure 1 gives the reporting framework for devicesrelated concerns, and Table 3 details reporting guidelines for MDAEs in some countries.

Reporting Framework for Medical Devices-Related Issues
A simple and brief schematic representation of medical devices-related reporting can be explained below:

Not-Reportable Incidents
As every adverse event cannot necessarily be documented, some regulatory authorities define not-reportable events as adverse events caused by patients' pre-existing health conditions. Similarly, events cannot be reportable if the shelf life expires before its use by the patients. Also, if the manufacturers mentioned the expected side effects in their product labeling, these cannot be considered reportable events. Above all, if the patients' abnormal use pattern of behavior    induced any untoward events, these can also not be reportable [14].

Social Media and Their Role in Materiovigilance
Social media, like LinkedIn, Facebook, Twitter, YouTube, help to provide users with rapid and up-to-date information on rational selection and undesired events and promote health-and science-related developments and issues [28,29]. They also contribute to sharing information related to medical device recalls if any defects are reported. This will ultimately make the users and practitioners aware of the latest regulatory actions or provisions related to the device. However, over-reliance on information disseminated on social media platforms for every piece of information may create havoc for users, especially physical hazards, and mental distress. Hence, critical analysis of information shared on social media with its source verification is essential to avoid potential misinformation because misinformation may be even worse than no information [28].

Recall of Devices
Devices are recalled for multiple reasons, some of which are defects in the products or their potential impacts on morbidity and mortality to the users [2]. The guidelines of Medicine and Healthcare Product Regulatory (MHRA) and GHTF stated that devices could be returned to their manufacturers or vendors as primary methods. Also, these can be alternatively subject to modification, remodeling, substituting of newer ones, or dismantling as part of a regular device recall [30]. Regulatory authorities like the FDA or device manufacturers can recall the products when deemed to pose any health complications to the patients. Whenever the manufacturers even voluntarily recall the products, they should notify the FDA immediately. The FDA may recall devices based on their categories or severity of harm and may update its website with reasons of such recalls [31]. Class I recalls apply to the highest risks to patients, Class II recalls refer to those with a moderate risk, whereas Class III recalls meaning those with low-risk profiles [32]. Since the recall list is quite comprehensive, a brief account of some medical devices recalled from the market within the last ten years has been presented in Table 4.

Role of Health Professionals in Reporting Device-Related Issues
Health professionals such as surgeons, physicians, nurses, and pharmacists can report medical device-related concerns by building and enhancing individual and institutional capacity to report and tackle the device-related adverse effects. This can be achieved with the database information system that generates signals for medical devices. They can also educate and train colleagues and patients to raise their awareness of the importance of Mv in device recalls if a fault should appear in practice since the main thing is the initiation and development of an institutional culture for reporting MDAEs for their future prevention [33].

Role of Consumers in Reporting Device Failures
Consumers in the USA are somewhat aware of reporting MDAEs like quality issues and administration errors experienced with devices and filling the Form FDA 3500B and reporting via MedWatch voluntary reporting system [34]. In Australia, the Therapeutic Goods Administration (TGA) has developed a website to empower the users' reporting practice [35]. Similarly, in New Zealand, the MedSafe system developed a form for the consumers to be filled in the Word document format and send via email on its website [36]. The reporting by the consumers helps practitioners, pharmacists, and policymakers to know the users' perspectives and concerns on devices in strengthening the reporting systems and ultimately in focusing on the quality products.

Challenges and Solutions Associated with Materiovigilance
As in the case of Pv programs, Mv also faces similar challenges to getting implemented up to the practitioners' and consumers' level. The consumers and practitioners generally perceive reporting as tedious and lack awareness on the significance and procedures of reporting (e.g., what, how, where and when to report the incidents). In addition, the lack of stringent regulatory mechanisms to make the reporting mandatory makes its implementation challenging in real practice settings. The practitioners' negative perception of MDAEs reporting as if these are being directed at reporting their mistakes has also become a significant barrier. Moreover, a lack of trained reporters and conducive facilities are also hindering the successful implementation of Mv [37]. Regulatory authority's initiation in affixing the mandatory package inserts and summary product characteristics (SPC) of the devices may help tackle some hindrances in implementing Mv.

Conclusion
Developed countries like the UK, the USA, New Zealand, Australia, and some developing countries like China and India have developed materiovigilance (Mv) mechanisms in reporting medical device-associated adverse events (MDAEs). Still, many developing countries lack such manufacturing facilities, rely on imports, and lack stringent Mv programs. Hence, policymakers must develop Mv programs to empower health professionals and consumers to report the MDAEs to prevent a recurrence. The package insert of medical devices must include a section highlighting the potential risks with their prevalence pattern. While the pharmacovigilance programs globally are taking good shape, much more must be done to initiate and strengthen Mv programs, at least in the countries reviewed in the present study but preferably globally.

Open Access
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