Materiovigilance Programme of India: Current status and way forward.

Postmarketing vigilance system for medical devices in India is not as vigorous as of drugs. W Materiovigilance involves post marketing surveillance of adverse events caused by medical devices. As per directive of WHO, many countries including India have established their own post marketing surveillance system. In India it is known as Materiovigilance Programme of India (MvPI). This article reviews the current state of MvPI, compares it with developed countries, identifies gaps, and recommends specific measure to strengthen the existing program.

Introduction

Materiovigilance is defined as a combined system of performance characterization, monitoring, identifying, collecting, reporting, and analyzing any untoward occurrence caused by medical devices. While pharmacovigilance deals with postmarketing surveillance of medications, materiovigilance deals with postmarketing surveillance of medical equipment including in vitro diagnostics. India is a USD 3.1 billion medical device market. However, for a long period, there was no proper vigilance system that monitors the adverse events related to medical devices.[1] Initially, the marketed medical devices were regulated according to the Drugs and Cosmetics Act, 1940 and Rules 1945. Later in 2017, an exclusive rule was framed to regulate the medical devices available in the Indian market known as Medical Device Rules, 2017.[2] The term medical device can be designated as any contrivance or device, machine, tool, grafting material, or tangible item used to help individuals or animals for the purpose of diagnosis, treatment, prevention, and disability management. In 2010, a major medical device adverse event occurred that forced well-known medical device manufacturer to withdraw all their medical device from the market that was being used for hip replacement. These devices were causing malfunctioning and threat to the life of patients. This happened because of the discharge of metallic particles into the blood circulation, and patients had to endure many operations, especially when metal implants were used. Other than this there are multiple incidences of serious adverse events reported from India. A patient received electrical burn injury as a result of defibrillator failure;[3] metal ions were found in the blood and soft tissue of patients following hip replacement surgery;[4] and a newborn died following overheating of the incubator.[5] Hence, it has become imperative to develop a surveillance system to identify any unwanted or unpredictable, undesirable, and unintended events related to medical device use. To overcome all these events, a necessary step was needed to be taken, for which the Materiovigilance Programme of India (MvPI) was launched by the Government of India.

Materiovigilance Programme of India

In the wake of the need to regulate the safety surveillance of medical devices in India, under the umbrella scheme of the Pharmacovigilance Programme of India (PvPI), the Ministry of Health and Family Welfare has authorized the MvPI, a system for monitoring the safety of medical equipment affiliated from the Government of India in 2013. The MvPI was formally launched on July 6, 2015, with the support of Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) as the National Coordinating Center (NCC). Among the increasing cases of malfunctioning in many medical devices and several other cases of device-related adverse events, leading to complications in patients and in most severe cases death, the importance and need of MvPI are escalating with each passing day. Later, in 2018 onward, the Indian Pharmacopoeia Commission (IPC) functions as NCC for MvPI besides as NCC for PvPI. This decision was essential to utilize the optimum resources, workforce, and other logistics for both the programs. As the infrastructure and capacity building in MvPI are one of the challenges, unlike drugs, the reporting tools, data collection, and assessment are different in nature. To ensure effective implementation of MvPI, it is recognized that the integration of biomedical engineering department at the hospitals/institutions is pivotal besides coordination with other departments. Therefore, the priority has been given to the institutes with biomedical/clinical engineering department (BMED) to function as medical device adverse event monitoring centers (MDMCs). Furthermore, preference is given to other departments also if they are intact with BMED. Involvement of BMED in MvPI is pivotal because most of the medical devices are designed/manufactured with engineering technology.

The MvPI aims at:

Creating a countrywide plan for monitoring patient safety

Examining the benefit–risk ratio related to a medical device

Creating evidence-based data for medical equipment associated with adverse events

Supporting the Central Drugs Standard Control Organisation (CDSCO) in making decisions about medical device regulation in the country

Exchanging safety-based information with various stakeholders in the industry

Collaborating with other health-care organizations and international agencies for information exchange and data management.

The IPC as NCC for MvPI currently manages 150 such MDMCs, pan India, besides soliciting the Adverse Drug Reaction Monitoring Centers under PvPI for adverse events reporting.[6] Both the stakeholders of PvPI and MvPI are being regularly trained for reporting through various tools available for reporting. The NCC aggressively works with the stakeholders to enhance the culture of adverse events (medical devices) reporting. Through education and advocacy, it is sensitized that reporting of adverse events is our professional and ethical duty by focusing on patient's safety at large. As per the Medical Devices Rules 2017, the Marketing Authorization Holder shall submit all medical device adverse events to Central Licensing Authority, i.e. CDSCO. Meanwhile, they submit a copy of such adverse events to MvPI also. The MvPI perform an initial assessment of the reported adverse events and perform a root cause analysis of the required adverse event to find out if any temporal relationships exist between reported adverse event and malfunction of the medical device. Then if any meaningful conclusion has arrived the NCCMvPI submits reports to CDSCO. In addition to this NCC-MvPI issues medical device alerts to all MDMCs for active surveillance of suspected medical devices. Also, NCCMvPI educates the general public to be aware of medical device safety and to report adverse events caused by household medical devices.

Different Centers under the Materiovigilance Programme of India

Under MvPI, initially, 10 MDMCs have been identified nationwide that work to report medical device-related adverse events (MDAEs) whose number has been increased to 150. Since the launch of the Programme, the reporting rate has also increased. More than 7000 reports have been submitted to IPC through MvPI. The MDMCs are responsible for proper identification, collection, and reporting of any suspected or confirmed MDAEs that come into five categories: not related, unlikely, possible, probable, and causal relationship, respectively. MDMCs should send the reported cases to NCC-IPC every month for review and analysis. The time frame set to report an MDAE after becoming aware of it is within 5 working days, and 30 calendar days is given to report the event after assessing its root cause.[7] IPC is the sole custodian of MvPI database. NCC is responsible to coordinate with all MDMCs in India and communicates all concerned issues to the CDSCO. In addition, they collaborate with international authorities as well and provide financial support to SCTIMST, the National Health Systems Resource Centre (NHSRC), and MDMCs. SCTIMST functions as the National Collaboration Centre and provides support in all technical matters. NHSRC works as a technical support partner in the Programme. It provides technical support and guidance on preparation of standard operating procedures, guidance documents, newsletters, training manuals, etc. Finally, all the issues are conveyed to the CDSCO, i.e., a national regulatory authority ensuring safety. It is responsible for taking all desired actions on recommendations by the NCC-MvPI. The organizational structure of MvPI is presented in Figure 1.

Figure 1

Organizational structure of MvPI. MvPI=Materiovigilance Programme of India

Global Postmarketing Surveillance Approaches

The United States of America, Canada, Japan, Australia, the United Kingdom, and Europe all have set up their own surveillance systems for active and passive monitoring of MDAEs. The USA has set up a worldwide recognized system called Food and Drug Administration (FDA) for the regulation of food, pharmaceuticals, vaccines, and medical devices. In the United States (US), a mandatory and voluntary scheme of reporting has also been suggested. Other countries such as the United Kingdom have their adverse event database and monitoring and reporting schemes.[8] All these countries have a recognized system and databases for medical devices which are listed in Table 1.

Table 1

Medical device regulatory bodies

Country	Medical device regulatory authority/database
USA	FDA MAUDE
Japan	PMDA
UK	MHRA
Australia	TGA
Europe	EMA
India	CDSCO

FDA=Food and Drug Administration, MAUDE=Manufacturer and User Facility Device Experience, PMDA=Pharmaceuticals and Medical Device Agency, MHRA=Medicines and Healthcare Products Regulatory Agency, TGA=Therapeutic Goods Administration, EMA=European Medicines Agency, CDSCO=Central Drugs Standard Control Organisation

In the United States of America, medical devices are needed to be authorized and approved by the FDA for their effective and safe use before getting introduced into the market. Device and radiological health center, an integral part of FDA, oversees medical device relabeling, manufacturing, and export and import all around the globe.[9] In Europe, the scenario is different as all medical device-related complaints are directly handled by the National Competency Authority (NCA) from the manufacturer, whereas it is mandatory for general practitioners, doctors, and nurses to report the event to both manufacturer and NCA. The manufacturers are required to submit an initial report of the serious adverse event within 2 calendar days. After this, if the manufacturer finds any relation between a medical device and death or any health problem, the assessment is needed to be appraised within 10 days. Any miscellaneous incident which is nonserious can be reported within 30 calendar days.[10] In Japan, medical devices are being supervised by the Pharmaceutical and Medical Device Agency which comes under certain rules and regulations that are needed to be fulfilled for certification, quality assurance, and licensing including Japanese medical products.[11] In Australia, while introducing any product in the market, the sponsor is required to submit all records of medical devices such as batch number, information on ingredients and a well-maintained sample of the life-threatening compound to the Therapeutic Goods Administration (TGA) to keep it as a record up to 5 years.[12] In Canada, “Health Canada” Regulatory Authority controls and makes sure that all medical devices are safe and rational for use by inspecting, evaluating, and investigating them in both phases: pre- and postmarketing surveillance. Moreover, Health Canada also regulates license application for both new and modified devices. In premarketing phase, the regulatory authority makes sure that all of the criteria that are required for filling license are up to the mark.

Indian Postmarketing Surveillance Approach

Postmarketing surveillance done by an Indian regulatory authority (MvPI) is gradually attaining momentum par with global regulatory authorities. Although the total number of reported adverse events is increasing yearly, from 40 events in 2015 to 897 in 2019,[13] [Figure 2] these are still less compared to other countries, not only in cumulative number but also in other safety factors including recall. In 2017, the USFDA recalled 30 medical devices and, in 2018, recalled 32 marketed medical devices for multiple reasons.[14] During the period 2017–2018, an Australian regulatory authority (TGA) received 5348 adverse event reports. A review of these incidences resulted in a recall of 27 products and communication of 41 hazard alerts.[15] In 2018–2019, TGA received 5874 adverse events and generated 5129 signals which resulted in recall of 55 products and generation of 68 hazard alerts.[16] Health Canada also reported a higher number of recalls during this period [Table 2]. However, throughout this period, the recall action or safety signals generated by MvPI from reported adverse events were negligible [Table 2]. It emphasizes that MvPI has a major step forward for data collecting and processing of adverse events and signal generation for recall action. Data collection is still limited to recognized medical colleges and hospitals, autonomous institutes, and importers. Larger involvement of private hospitals, nursing homes, and laboratories has to be promoted. Moreover, the data generated by MvPI are not available in the public domains which edge the manufacturers’ and stakeholders’ real-time aware of adverse events and delay corrective action.[1718]

Figure 2

Adverse events reported to MvPI on a yearly basis. MvPI=Materiovigilance Programme of India

Table 2

Trends in recall of medical devices in abroad and India

Country	2017	2018	2019	2020
Australia	N/A	27	55	614
US	30	32	49	32
Canada	1422	1549	1355	1301
India	N/A	N/A	N/A	N/A

N/A=Not available

Regulatory Gap

India does not have specific guidelines for MvPI as are available in the EU and the US for their post-marketing surveillance programmes on medical device safety. The tools and guidelines for signal detection are to be developed, and causality assessment should be validated. MvPI appears to be robust on paper, yet the annual performance report of MvPI and monitoring centers regarding collection and submission of data is not published. The analysis of reported adverse events and action taken toward reported adverse events is not in public domain. Many devices are still out of notified list.

Penalties for Device Failure

In the US, the top 10 big medical device firms have paid more than $600 million dollars to medical practitioners and their clinics as it is vital for pharmaceutical manufacturer/medical equipment manufacturer to pay the liabilities. In 2016, a firm known as Olympus Corporation of America had to pay around $623.2 million dollars as legal action against them from court in which they were alleged to bribe doctors and all hospital staffs. Another company under the name of Medtronic Inc. was engaged to pay $2.8 million dollars as compensation to a patient as health-care system was bribing the doctors by giving monthly bonus to use faulty and malfunctioned medical equipment making the treatment way too expensive.[19]

Way Forward

If the MvPI has to flourish, the participation at grass root level has to be escalated. For that, the awareness among health-care professionals and the public about MvPI has to be amplified. Potential barriers in reporting MDAEs such as lack of awareness of reporting systems and not knowing what exactly to report and the fear of impact on reputation and medicolegal issues are to be managed. Academic curricula for all health-care and paramedical courses should be updated to incorporate MvPI, and the practice of reporting MDAEs should be instilled during internship and postgraduate programs to provide solid foundational training. The Medical Council of India should make MvPI a compulsory learning for all doctors to renew their licenses. Collaboration with medical institutions and corporate hospitals will increase MDAE reporting culture and practice. Keeping implant registry at hospital level and pasting information of implanted device at patient outpatient department card need to bring as routine practice. The capability of clinician's suspicion level that adverse events happened might correlate to a medical device used is warranted. At present, pharmacovigilance is incorporated into NABH; similarly, the incorporation of MvPI to NABH fulfillment criteria is also suggested.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.