INTRODUCTION:

As per World Health Organization (WHO) definition “Medical device” means any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purposes of:¹

· Diagnosis, prevention, monitoring, treatment or alleviation of disease

· diagnosis, monitoring, treatment, alleviation of or compensation for an injury

· the investigation, replacement, modification, or support of the anatomy or a physiological process

· supporting or sustaining life

· control of conception

· disinfection of the medical device

· Providing information for medical purposes using in vitro examination of specimens derived from the human body and which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means”.¹,²

Transformation in the medical device industry is ongoing and is more required, in such a way that innovative information technology, Artificial Intelligence (AI), networking and other biomedical and engineering principles are incorporated.²

The global market of medical devices has a value of $456.9 billion estimated in 2019. This market has seen annual compound growth of 4.4% since 2015. The expected growth by 2023 is around 6.1%.³

Due to technological advancement and improving facilities, the medical device market has seen exponential growth. It is due to the spread of infectious diseases and the continued prevalence of chronic conditions amongst the population.³

In the year 2014, the World Health Assembly (WHA) considered a resolution for the strengthening of the regulatory system for medical devices, named WHA 67.20. In the resolution, it is mentioned that “effective regulatory systems are an essential component of the health system and their strengthening contributes to better health outcomes”.⁴

According to WHO Global Model Regulatory Framework, it is clear that many countries don’t have the financial resources and technical expertise to transition from the unregulated market into a regulated environment in a single go or single programme. Therefore, WHO recommends a progressive, stepwise approach for regulating medical devices.⁴

As suggested by WHO there is a need for law, rule or act for a medical device. It further elaborates the fact that the regulation and governance of medical devices should be in coordination with the regulation of other medical products like medicines and vaccines.⁴

The thalidomide tragedy paved the way to Pharmacovigilance.⁵ Many developed countries have recognized the global need for regulating medical devices to ensure access to safe, effective, and quality medical devices, and have introduced new or amended their existing regulation in such a way that it provides necessary provisions in effective implementation of medical devices manufacture, sale, quality, efficacy etc.^4,6

Glancing at the developed nations:

In the developed nations like the United States (US), they have a separate program called ‘Center for Devices and Radiological Health (CDRH)’.⁷ This holds the authority for regulating all activities like manufacturing, repackaging, relabeling, and/or import of medical devices to be sold in the United States.⁶ 510(K), also known as premarket clearance, is used for notifying the Food and Drug Administration (FDA) before marketing devices in the states.⁸ In addition to the medical devices, the CDRH also regulates the non-medical device including electronic devices like X-ray machines, toasters, or microwave ovens. Similarly, the devices to be used in the ‘European Union’ undergo a ‘conformity assessment’ which means a regulatory check at the quality of the product. A passed device has a ‘CE (Conformité Européenne) mark’.⁹

About the SEARN (South-East Asian Regularity Network):

Taking hints and ideas from the developed countries, the mission of the SEARN lies mainly in strengthening the existing regulatory standards and collaborating for developing new ones. The convergence of the different countries allows the countries to share their burden and challenges, enabling their respective National Regulatory Authority in fulfilment and betterment of public health.¹⁰

The present article attempts to study such regulatory provisions for medical devices in South-East Asian countries and identify the gap. The SEAR (South-East Asia region) consists of countries such as Indonesia, Sri Lanka, Thailand, Timor Leste, Bangladesh, Bhutan, Democratic People’s Republic (DPR) of Korea, India, Maldives, Myanmar and Nepal. According to the strategic planning employed and cost-effectiveness that is being studied, WHO has divided the nations into two parts, namely SEAR B and SEAR D. The SEAR B includes Indonesia, Sri Lanka, Thailand and Timor-Leste whereas SEAR D includes Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Maldives, Myanmar and Nepal.¹¹

WHO SEARN is responsible for the regulations of the medical product. Herein, the medical product includes medicines, vaccines, biological, medical devices and diagnostics that are used for ‘humans’ in the eleven countries of the South-East Asia Region (SEAR)
. WHO South-East Asia Regulatory Network (SEARN) was established in April 2017, to enhance information sharing, collaboration and convergence of regulatory practices across these eleven countries for guaranteeing access to high-quality medical products. There is a WHO South-East Asian regional office that provides the secretariat support required by the network.¹²

Every individual requires timely access to both affordable and quality medical products that are both safe and effective. This is for all the countries in the South-East Asian region and beyond.¹⁰

Why is there a need for collaborations, when regulations exist at a national level?

The first and foremost thing that is exchanged is information. Communication regarding all the policies, guidelines, standards, procedures, and outputs regarding the regulated products between the Regulatory agencies of the nation, thereby creates a healthy environment. This will surely benefit when it comes to serious adverse events (SAE) and errors, along with detecting shared efficacy.¹⁰

The collaboration strengthens the system by facilitating and supporting regulatory improvement while providing competency to the regulatory authorities in the system. It also allows the regions in identifying and developing their potential. The collaboration promotes approaches based on international standards. Convergence allows for good regulatory practices as well.¹⁰

METHODOLOGY:

The relevant information was obtained from the official government websites of the respective country. Also, the published documents such as official gazette notification, guidelines were used for collecting the information. However, seldom review articles and editorials were also looked through. The authors have attempted to gather information on the medical device regulation available in these countries and whether they were act, rule or guideline under which devices are regulated. The information about the year since these regulations were effective, adverse event reporting authority, channels of reporting any adverse event related to the device, whether reporting of the adverse event if a volunteer or mandatory, Quality Management System followed and data management tool was also tried to obtain. All the available and accessible data from the web search was compiled. The collected information was collated, compared and analyzed, and is now presented as in table 1.

Table no. 1 The following table represents the comparison of the countries based on six parameters namely; medical device regulation, medical device standard and quality compliance, SAE reporting authority, whether reporting is voluntary or mandatory, AE reporting tool and data management too

Name of country	Medical device regulation	Medical device standard and quality compliance	SAE reporting authority
Bangladesh	Registration guideline for medical device, 2015 ¹³	International Organization for Standardization (ISO) 13485 ¹³	Directorate General of Drug Administration (DGDA) ¹³
Bhutan	Medicine Act of the Kingdom of Bhutan, 2003 ¹⁴	N/A	Drug Regulatory Authority (DRA) ¹⁴
Democratic People’s Republic of Korea	Medical Device Act, 2003 ¹⁵	ISO 13485¹⁵	Ministry of Food and Drug Safety ¹⁵
India	Medical Device Rule, 2017 ¹⁷	ISO- 13485 and Bureau of Indian Standards (BIS) ¹⁷	Central Drug Standards Control Organization (CDSCO) ¹⁷
Indonesia	Legal framework, the regulation regarding medical device and household products marketing, 1991 ¹⁹	ISO 13485²⁰	NRA (National Regulatory Authority) ¹⁹
Maldives	Medical Device Bill has been introduced. However, yet to be implemented ²¹	N/A	Ministry of Health/Maldives Food and Drug Authority ²²
Myanmar	N/A	N/A	Food and Drug Administration, Myanmar ²³
Nepal	N/A	N/A	Department of Drug Administration, Ministry of Health and Population ²⁴
Sri Lanka	Guideline under ‘The Cosmetics Device and Drug Act No. 27’, 1980 ²⁵	N/A	CDDA (Cosmetic Devices and Drug Regulatory Authority) ²⁵
Thailand	Medical Device Act B.E 2551 1988 and the B.E 2551 in 2008 ²⁷	ISO 13485 ²⁸	FDA (Thai Food and Drug Administration) ²⁷

Table 1 continued

Name of country	Reporting volunteer or mandatory	AE reporting tools	Data management tool
Bangladesh	N/A	N/A	N/A
Bhutan	N/A	N/A	N/A
Democratic People’s Republic of Korea	N/A	Medical Device Adverse Event Reporting Form No-01 ¹⁶	N/A
India	Mandatory ¹⁷	Medical Device Adverse Event Reporting Form can be sent to IPC ¹⁸ Email- mvpi.ipcindia@gmail.com Phone- 1800-180- 3024 ¹⁸	N/A
Indonesia	Mandatory for sponsor ¹⁹	N/A (we couldn't access any form of tool through online search)	N/A
Maldives	N/A	N/A	N/A
Myanmar	N/A	N/A	N/A
Nepal	N/A	N/A	N/A
Sri Lanka	N/A	e-Adverse Event Reporting Form is available ²⁶	N/A
Thailand	Mandatory ²⁹	Ror Mor Por-1 (consumer form), Ror Mor Por-2 (Field Safety corrective action form)To be emailed or handed in-person to 'Technical and Planning Division' of Health Product Vigilance Centre (HPVC) of Thai FDA ²⁹ Emailed as pdf at: adr@fda.moph.go.th²⁹ Uploaded as excel at: http://thaihpvc.fda.moph.go.th²⁹	N/A

Countries at a glance:

Bangladesh:

The manufacture, sale, import, and distribution of medical devices in Bangladesh are governed under the Drug Act, 1940 and the Drug (control) Ordinance 1982 rule.¹³ Bangladesh showed an annual growth of 10% in the last decade. The market size was around 1.6 billion in the year 2015. The best part is that most of the products like vaccines, hormonal and anti-cancer drugs are more locally manufactured than imported.³⁰ Bangladesh joined the WHO program in the year 2013 and started submission of ADRs to VigiBase around December 2014.³¹ In 2015, the regulatory system in Bangladesh harmonized and standardized their practice with the introduction of “Medical Device Registration Guideline”. The guideline in Bangladesh is based on the guidelines of the Global Harmonization Task Force (GHTF). They have formulated guidelines and standards for both medical device and their labelling. For labelling, they follow ISO and Global Harmonization Task Force Guidance document GHTF/SG1/N70:2011. And, for Clinical Investigation of Class B, C, and D, DGDA ensures that investigation is proceeded as per standards i.e. ISO-14155.¹³ The reporting period for an adverse event is within 10 working days.¹³

Bhutan:

According to Bhutan, a medical device is defined as “any article, device, instrument, machine used for diagnosis, prevention, measuring, restoring, or modifying the function of the body for some health purpose”. Currently, for the manufacturing of the device in the country, only a general administration document is needed, such as a “letter of authorization” or dealership certificate, and no regulatory approval from the DRA is needed. For strengthening the regulatory system, the DRA is continuously seeking technical assistance from SEARN. Both the Government of Bhutan and the health ministry are looking forward to efficiently establish medical device regulation in the country for effective and standard medical devices with lower safety issues.¹⁴

Democratic People’s Republic of Korea:

· In DPR Korea, there is a proper provision for the recall of medical devices causing serious harm to the patients. There are two types of recall, the firm initiated recalls which is voluntary and government-initiated recall.¹⁵

· On-site audits are mandatory in DPR Korea for class 2, 3, and 4 devices category but it is elective for class 1^st device category.¹⁵

· Death and life-threatening events should be reported within seven days and all other adverse events should be reported within fifteen days to the “Ministry of Food and Drug safety”.¹⁵

India:

In India, Medical Device Rule was introduced in the year 2017 and is effective since 2018. Before the Medical Device Rule, 2017; devices are regulated under the Drug and Cosmetic Act, 1940 and Rule 1945. In-depth risk-based classification is available in India for the devices.¹⁷ Unlike many other countries, India strictly follows this system.³²

All the devices sold should bear a general ICAC (Indian Conformity Assessment Certificate). ³³ Wherever this is unavailable, International Organization for Standardization (“ISO”) or the International Electro-Technical Commission (“IEC”), or any other Pharmacopoeial standards is used.³² In 2015, the Government of India (GOI) approved the Materiovigilance Program of India (MvPI) to monitor and assess the safety of medical devices.³⁴ The main aim of the program is the collection and analysis of the adverse event reports generated due to medical devices.¹⁸ It is a voluntary program and anyone can be a part of it. India has come forward in the COVID-19 times in regulation of PPE kits and masks, through an Adverse Event Reporting Form.³⁵ Within 15 days of an adverse event bought into notice it has to be reported to the authority.¹⁷ ‘SUGAM’ portal is available for registration of medical devices, drugs, vaccines, etc. It has paved the way for technology in the Indian pharmaceutical industry.³⁶

Adverse event monitoring for hospitals in India is done via the Intensive Event Monitoring (IEM) programme that allows the pharmacovigilance officer to collect the same from various hospitals.³⁷

An elaborate methodology for the required regulatory action has been stated in the guidance document for MvPI. Field safety corrective action form is designed for the manufacturer to submit the report of the devices that are being recalled from the market on the behalf of its safety profile.¹⁸

Indonesia:

The SAE reporting period for any sponsor with a marketing license is once per year.¹⁹

Nepal:

The Government of Nepal has approved a directive in 2017 which came into effect in November 2020. The “Directive on Health Technology Product and Equipment, 2074” discusses quality testing, import, export, records to be maintained, registration of products, monitoring, testing and inspection of products, maximum retail price along with the definition for everything. It provides the format for all the certificates necessary for approval.²⁴ Nepal’s medical equipment and drug supply are one of the industries for prospective development. Imports have improved in recent years and even the numbers of medical facilities have increased majorly. With this, there has been a good amount of sales. The majority of imported devices come from the U.S and India. X-ray machines, ultra-sonographic machines, electrocardiogram machines, and other testing equipment are the most common medical devices that are imported into the country. There are ample opportunities for development as the demand remains high.³⁸

Sri Lanka:

The ‘Guideline for registration of Medical Device’ document is provided by the “Cosmetic Device and Drug Regulatory Authority” (CDDA) and helps in guiding with purpose, background, scope, definition and even the registration procedures. In the registration procedure, the responsibility of the applicant, basic requirements are discussed. The labelling of the Product Information Leaflet (PIL) is provided in detail. There is also a provision mentioning the requirements for multiple devices. A clear and concise flow chart for validation of registration is provided in the guidelines.²⁵

Thailand:

For local reporting:

Fatal or life-threatening events must be reported within 24 hours of awareness.³⁹ Non-fatal or non-serious events must be reported within 7 days of awareness.³⁹

The Suspected Unexpected Serious Adverse Reactions (SUSARs) with life-threatening symptoms must be reported to Institution Review Board (IRB) using the Council for International Organizations of Medical Sciences (CIOMS) form, no later than 7 calendar days since awareness of the event.³⁹

SUSARs that are non-fatal must be reported to the IRB using the CIOMS form within 15 calendar days of awareness of the event.³⁹

The Market Authorization Holder or the Specification Provider is obliged to report problems related to medical devices including device defects or adverse effects and the corrective actions.²⁹

Timor Leste:

Timor Leste has a drug regulation that is seldom used for devices as well.⁴⁰ Their basic health facilities have improved but accessing medical devices and their benefits is still a major challenge. The World Bank has extended its support and helped in establishing a new system of an autonomous medical store called SAMES (Timor Leste’s Medical and Pharmaceutical Supply Agency). They have been actively working in national government hospitals and other sites for ensuring continuous medical supplies. Though slow in progress, the medical health facilities have improved tremendously from the last ten decades. They now have health facilities, doctors, nurses and midwives even in their villages. SAMES have a management system for pharmaceutical substances called mSupply.⁴¹

RESULT:

It was observed that for most nations, a separate Act does exist for medical devices. In this article; we have attempted to understand the varying contrast in guidelines across various countries of SEARN. Some of them have an elaborate set of rules/guidelines laid out for device regulation as in the case of India, Bangladesh, Thailand, and Sri Lanka. However, some of the nations like Timor Leste, Bhutan, and Nepal have a major gap area in this field as shown in Figure 1

DISCUSSION:

For drugs, the ‘Uppsala Monitoring Centre’ provides a web-based facility for member countries in Individual Case Safety Report (ICSR) management, analysis and signal detection. This facility is very well received and used by all the WHO member states for handling the AE of the drug.⁴² Whereas, for WHO SEARN countries no robust tool for analysis of medical device Adverse Event is present. These countries might be managing and analyzing the adverse events of the medical device on their own using in-house databases or excel or computer-based systems. Therefore, there is an urgent need for these kinds of tools for medical device management.

Through the article, it is understood that the nations across the SEAR have varying rules/guidelines/acts. Gap area in India, is also identified in the sense that there isn’t a clear distinction of SAE reporting according to medical device classification. This was, however, observed to be there in Thailand's Medical Device Act. The need of the hour suggests that all the nations should join together to implement the policy of separate rule for medical device regulation.

CONCLUSION:

Harmonization of the medical device regulation across the South-East Asian Region (SEAR) will help in providing a convergent standard for quality and safety guidelines across the entire region. This article will be also helpful for the policymakers as it provides a concise view of all data available.

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Received on 20.04.2021 Modified on 12.05.2021

Asian J. Pharm. Res. 2021; 11(3):173-179.

DOI: 10.52711/2231-5691.2021.00032