Drug-Device Combinations And Materiovigilance In The Cardiology Department Of A Tertiary Care Private Corporate Hospital (2024)

A combination product is a product composed of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product. These products are helpful for patients enduring with serious illnesses and conditions like cancer, cardiovascular disease, sclerosis, diabetes, etc. On the contrary, drug-device combination products have also brought forth a contemporary dimension in medical product development and regulatory approval [1]. Examples of combination products include prefilled syringes, pen injectors, auto-injectors, inhalers, transdermal pumps and patches, kits containing drug administration devices or components, drug-eluting pacemaker leads, antiretroviral-loaded intravagin*l rings, drug-coated balloon catheters, hormonal subcutaneous implants, etc [2]. As per section 62(4) of the Medical Devices Regulations, a medical device incident refers to an occurrence associated with a failure of a medical device or a deterioration in its effectiveness, or any inadequacy in its labelling or in its directions to be used that has led to the death or a consequential deterioration in the state of health of a patient, user, or another person. Drug- device combination products are of important role within the diagnosis, monitoring, and management of various diseases. While the employment of medical devices benefits patients immensely, they also carry possible threats and potential risks. So, it is important to make sure the safety and efficacy of the medical devices during each stage of their development [3]. This study focuses on materiovigilance program in assessing the benefits and risks related to medical devices and combination products. The thought of materiovigilance was first originated when Johnson & Johnson hip replacement system was withdrawn globally due to their complications and harmful effects. One of the important aspects of this program is to monitor medical device-associated adverse events (MDAE), and it also helps to generate awareness among the healthcare professionals about the importance of MDAE reporting. They also play a vital role in analyzing the risk-benefit ratio of medical devices and collaborating with other healthcare organizations and international agencies for the exchange of information and data management [3]. Materiovigilance includes the identification, collection, reporting, and analysis of any unwanted occurrences related to the use of medical devices and also the protection of a patient’s health by preventing its recurrences. Drugs Controller General of India established the Materiovigilance Program of India (MvPI) at Indian Pharmacopeia Commission (IPC), Ghaziabad on July 6, 2015. In 2017, the Government of India issued the Medical Device Rules for regulating medical devices used throughout the country and these rules came into effect on 1st January 2018. The government had regulated or notified 37 categories of medical devices as drugs until February 11, 2020. On February 11, 2020, the Government of India gazetted two important notifications – a new definition of medical devices and the Medical Devices (Amendment) Rules, 2020. These rules came into effect on April 1, 2020. As per this rule, all medical devices in India will be regulated as “drugs”. All medical devices which weren’t notified until February 11, 2020, will then be covered by the new definition of medical devices and can be observed as “Non- Notified Medical Devices”. The Central Drugs Standard Control Organisation (CDSCO) released two notices on September 3, 2020, including the classification of non-notified medical devices and in-vitro diagnostic devices (IVDs). The CDSCO has classified almost 1866 medical devices and 80 IVDs. There are 24 categories of medical devices and 3 Categories of Non-Notified In-Vitro Diagnostic Medical Devices defined by CDSCO. Materiovigilance Programme of India provides a robust, sustainable, and scaled surveillance of all medical devices, thereby encouraging patient safety related to medical devices employed within the healthcare industry in India [4]. Several serious medical devices associated adverse events (MDAE) were received by the Indian Pharmacopeia Commission till now. Numerous types of cardiac implants, including pacemakers, Implantable Cardioverter Defibrillators (ICDs), Left Ventricular Assist Devices (LVADs), Cardiac Resynchronization Therapy devices (CRTs), Transcatheter Aortic Valve Replacement (TAVR), cardiac monitoring devices, artificial heart valves etc. are widely being used for treating various cardiac disorders [5]. Devices such as drug-eluting stents and bioabsorbable stents incorporate drugs like sirolimus, everolimus, zotarolimus, pacl*taxel etc. in microfabricated drug reservoirs on the surface. These medications help to inhibit the growth of cells that can cause the artery to become narrowed or blocked again [6]. Various reports had shown possible hypersensitivity reactions related to the utilization of the sirolimus-eluting stent, a few of which are fatal and patients receiving the sirolimus-eluting stent should be monitored for hypersensitivity associated symptoms such as rash, hives, itching, fever, difficulty breathing, pain, and blood pressure change. Thrombosis, anxiety, and bronchospasm caused by drug eluting pacemaker lead, epinephrine autoinjector, and inhalers were also reported. In multiple instances, some devices were recalled due to the risks and damages they caused to users. Thus, drug-device combination products are not devoid of adverse events [7]. Therefore, strict vigilance of drug- device combination products used for diagnosis, monitoring or treatment of various cardiovascular diseases is the need of the hour in order to ensure health safety patients and reduce the recurrence of the events. Therefore, this study aimed to categorize the medical devices and collect, collate and analyse the data on medical device related adverse reactions in the Cardiology department, with special focus on drug-device combinations.

MATERIALS AND METHOD

A prospective observational study was carried out in the Cardiology department of a tertiary care private corporate hospital for a period of 6 months from July to December 2022. All medical devices and drug-device combinations for diagnostic, monitoring and therapeutic purposes, both external and implanted devices used in the Cardiology department were categorized into “notified medical devices” or “newly notified medical devices” using the CDSCO classification. All inpatients of the Cardiology department were closely monitored for any medical device associated adverse reactions and all types of adverse reactions, whether serious or non-serious, pre-known or unknown were recorded after confirming with the clinician’s report, irrespective of established causal relationship between event and medical device. The biomaterial used in each medical device and its safety profile was also thoroughly reviewed. Data on suspected adverse reactions related to medical devices were reported to the NCC-MvPI through the materiovigilance centre of the hospital using the Medical Device Adverse Event reporting form Version 1.1, a five-page editable form. Information such as the description of the suspected adverse reaction, details of the device, reporter, manufacturer and the regulator etc. were furnished through this form. The data thus collected were pooled and analyzed at the end of the study period. They were classified into serious, non-serious, preknown or unknown adverse reactions. Description of the device and associated risks to the users were studied thoroughly. The devices were also classified as Class A- Low risk devices; Class B- Low to moderate-risk devices; Class C- Moderate to high-risk and Class D- High-risk devices by following the CDSCO categorization.

RESULTS

One thousand and twenty-nine devices used in sixty patients of the Cardiology department were closely monitored during the study period for any possible medical device associated adverse reactions. The mean age of the study subjects was 53.47±21.83 years (range:1 to 85 years) and the mean duration of hospitalization was 4.97±2.28 days (range:2-7 days) Of these, 45 (75%) were male patients. The demographic details are presented in table 1.

Figure 2: Medical Devices Suspected With Adverse Reactions

DISCUSSION

The current study evidenced that the use of medical devices benefits patients immensely but they also carry significant risks to the patients. The use of cardiac devices including pacemakers, catheters, sheath, balloons, guidewires, drug eluting stents implantation are increasing in number (8). Today a number of different medical devices are available for various cardiac procedures. The MvPI had been established to ensure the safety of medical devices including cardiovascular devices. The US Food and Drug Administration (FDA) defines high-risk devices as those that “support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury” and include such products as pacemakers, defibrillators, implanted prosthetics, and high frequency ventilators (9).The high-risk medical devices used in the cardiology department during the current study include drug-eluting coronary stents, mechanical valves, pacemaker generators, and pulse generators. The most commonly used high-risk (Class D) medical devices in cardiac patients were permanent pacemakers and drug-eluting coronary stents. Eighteen suspected adverse reactions associated with Class C (moderate-high risk) and Class D (high risk) medical devices in the Cardiology department were identified and reported during the study period. Of these, only one was serious and the patient recovered after device removal and surgical intervention. The remaining were non-serious and does not produce any harm to the study population and the patients recovered within one to three days after exposure to the adverse reactions such as fever, headache, hematoma, blisters etc. The details are presented in Table 6.

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