When medical device manufacturers are considering placing devices on the market, they face the challenge of understanding the regulatory environment in different jurisdictions and the regulatory requirements that apply to them and their devices. Medical device regulators, as they evolve their regulatory frameworks in a particular jurisdiction, look for solutions to challenges they face from other countries and regions. Groups of countries in different parts of the world have looked to reduce barriers to trade by establishing a single market with common regulatory requirements.
Regional Comparison
Critical differences in the EU and ASEAN structure and mode of operation affect the regulatory frameworks for medical devices in the respective regions. Structurally, the EU member nations have conceded some degree of sovereignty to the EU, with mutual acceptance of regulatory decisions, whereas the ASEAN is structured as an intergovern-mental organization. The EU has a parliament, while the ASEAN has an inter-parliamentary assembly that does not have authority over member nations. Several member states in the EU have adopted a common currency, whereas the ASEAN maintains separate currencies, preferring to encourage coordination and cooperation among financial ministers. The EU has 23 official languages, while the ASEAN has agreed to use English for meetings and correspondence.
Evolution of Regulations for Medical Devices
An analysis of the regulations for medical devices in the EU and ASEAN reveals considerable similarities in both structure and content.Regulators from these regions interact and share experiences, best practices, and ideas, learning from each other’s work. Different regions update their regulatory framework at different times and in the context of their experience up to that point. Updates in one region become informative to the other region. This interaction can be seen in the timeline shown in Figure 1 and is evidenced by matching text found in many parts of the ASEAN MDD and EU Regulation. As illustrated in Figure 1, the EU published its new regulations for medical devices and in vitro diagnostics in 2017 and is in the process of transitioning to full implementation.
European Union (EU) and Association of Southeast Asian Nations (ASEAN) medical device directives and regulations: timeline of key milestones. Abbreviations used: AHWP, Asian Harmonization Working Party; GHTF, Global Harmonization Task Force; IMDRF, International Medical Device Regulators Forum; AMDD, ASEAN Medical Device Directive.
The Association for the Advancement of Medical Instrumentation (AAMI) advocates that regulators work regionally and globally. This work is resource intensive, and no one country on its own can afford to create and maintain the structure to regulate devices in today’s global marketplace. Furthermore, harmonizing standards is critical. Harmonization helps to provide market access for all manufacturers and increases the likelihood that safe and effective devices are accessible to patients.
Three key sources have influenced the development of regulations for medical devices:
- The Global Harmonization Task Force (GHTF), which has encouraged a convergence in standards and regulatory practices related to the safety, performance, and quality of medical devices and has promoted technological innovation and international trade.
- The International Medical Device Regulators Forum (IMDRF), which took over the GHTF’s mission in 2012, provides a means for discussing future direction in medical device regulatory harmonization.
- The Asian Harmonization Working Group, which studies and recommends ways to harmonize medical device regulations in Asia Pacific (including ASEAN) and other regions.
Directives and Regulations
Directives are legislative acts that set goals for member nations to achieve. Directives are not binding restrictions, and member nations decide how the directive is achieved. As such, the ASEAN MDD allows each member country to execute provisions of the directive independently.
Harmonization helps to provide market access for all manufacturers and increases the likelihood that safe and effective devices are accessible to patients.
The EU 2017/745 is a regulation, which is an act that is binding upon all member countries of the union. This regulation supersedes national laws of member nations.
Both directives and regulations have the impact of leading to greater harmonization across the respective region. Regulations tend to accelerate this harmonization and address both the outcome and methods.
Essential Principles
Both the ASEAN and EU recognize that devices must achieve the performance intended by manufacturers, that they should be designed in a way that is suitable to that purpose, and that they should be safe and perform as intended.
The ASEAN has developed the Common Submission Dossier Template, which requires manufacturers, in all ASEAN jurisdictions, to share the relevant Essential Principles (EPs) and methods used to demonstrate conformity.
The EU 2017/745 Regulation stipulates General Safety and Performance Requirements (GSPRs) that devices must meet; these can be used as inputs to the design and development process. The outputs of design and development can be verified and validated, as appropriate, against the GSPRs, thereby providing evidence and documentation to demonstrate compliance.
EPs and GSPRs have much in common; however, in some instance, GSPRs have additional detail or more specificity compared with EPs.
Collecting and sharing evidence regarding marketplace acceptance supports regulators and standards developers and ultimately enhances the safety and effectiveness of devices.
Role of Standards
International standards are building blocks for harmonized regulatory processes to ensure the safety, quality, and performance of medical devices. Regulations tell manufacturers what to do, while consensus standards tell them how to do it. Compliance with recognized standards may be used by a medical device manufacturer to demonstrate compliance with the relevant EPs/GSPRs of medical devices. Both the EU 2017/745 Regulation and ASEAN MDD stipulate a role for standards as a voluntary means by which a manufacturer can demonstrate conformance with regulatory requirements. In the EU, if the manufacturer does not use harmonized standards, then they have to justify this technically, scientifically, and clinically to the notified body.
AAMI prefers global solutions, embracing the philosophy of “One standard, one test worldwide.” The association stresses openness, transparency, and due process, with representation from all stakeholders in standards development. Unless specific national conditions demand divergent national safety standards, they should be avoided. AAMI promotes safety and effectiveness of health technology, as well as access for care providers and patients. Standards promote regulatory, clinical, and patient acceptance of new technologies and reduce technical barriers to trade.
Standards supporting regulation across the medical device life cycle are important. Collecting and sharing evidence regarding marketplace acceptance supports regulators and standards developers and ultimately enhances the safety and effectiveness of devices.
Competent Authorities
The ASEAN and EU require member states/countries to select and identify Legal Information Authorities and Competent Authorities for Medical Devices (CAMDs), respectively (Table 1). This authority usually is the individual member state’s ministry of health or an agency connected to the ministry of health. In the EU, the European Commission is responsible for properly executing regulations and for coordinating the activities of the member states.
Member countries/states: Association of Southeast Asian Nations (ASEAN) Legal Information Authorities and European Union (EU) Competent Authorities for Medical Devices.
Stakeholders
The ASEAN and EU recognize similar parties in the supply chain for medical devices. Both entities recognize the importance of organizations involved in the life cycle of a device—starting with its design and moving through manufacturing, distribution to the user, and monitoring for safety and performance. Although they use somewhat different terminology, both the ASEAN and EU recognize the pivotal role and responsibilities of the organization whose name is on the product. This organization has overall responsibility for the life cycle of the product, whether it performs the activities itself or has other organizations undertake some or all of the activities on its behalf (Table 2).
Terminology used for parties in the supply chain in the Association of Southeast Asian Nations (ASEAN) Medical Device Directive (MDD) and European Union (EU) 2017/745 Regulation
Defining Medical Devices
The ASEAN MDD and EU 2017/745 Regulation define medical devices similarly, with both drawing from past versions of EU directives and GHTF documents. Standards from the International Organization for Standardization and AAMI also use the same sources for defining medical devices. The definitions capture the purposes of diagnosis, prevention, monitoring, treatment, and alleviation of disease or compensation for an injury; investigation, replacement, or modification of the anatomy or physiological processes; or control conception.
The EU 2017/745 Regulation definition includes, for the first time, equipment for sterilization of medical devices as devices in their own right. Prior to this, sterilization devices fell outside of the definition of medical devices. With this change, sterilization equipment falls into the category of a medical device rather than accessories under the EU Medical Device Regulation.
Items and equipment with features that are characteristic of medical devices but don’t have specific medical purposes, having only cosmetic purposes (e.g., liposuction equipment, nonprescription contact lenses), are listed in an annex in the EU 2017/745 Regulation and regulated as if they are medical devices.
Classification of Medical Devices
As shown in Table 3, risk is classified similarly in the ASEAN MDD and EU 2017/745 Regulation. The level of rigor and third-party oversight increases with risk level. In addition, within each classification level, additional oversight can occur for various types of devices for both the ASEAN MDD and EU 2017/745 Regulation. The differences that do exist may create restrictions to trade and increased cost to manufacturers. The ASEAN MDD risk classification appears to be based on the IMDRF model (former GHTF model and Food and Drug Administration classifications).
Risk classification in the Association of Southeast Asian Nations (ASEAN) Medical Device Directive (MDD) and European Union (EU) 2017/745 Regulation
The EU has groups of devices within a classification that have additional levels of oversight, such as reusable surgical instruments, Class I devices that are sterile or have a measuring function, Class IIb implants, and custom-made Class III implants. In the EU, as oversight increases, it does so consistently across the EU member states. Historically, the EU has faced challenges of uniformed interpretation of medical device relations by member states. This latest set of regulations attempts to address these issues.
Regulatory Authorities and Notified Bodies
The ASEAN Regulatory Authorities have broad responsibilities. The ASEAN requires manufacturers to have devices assessed by each member state in which a device is marketed. Member states have the authority to control the import, manufacture, export, distribution, transfer, use, and sale of medical devices within that member state’s jurisdiction.
In the EU, conformity assessment activities have been delegated by CAMDs to designated organizations called notified bodies. A manufacturer can select a notified body in any member state, and after a manufacturer’s systems and, where applicable, its devices have been assessed by one notified body, it can be marketed throughout the EU. As required by the classification of the device, notified bodies are responsible for checking the design of devices, reviewing clinical evidence, and auditing the effective implementation of the quality management system.
Medical Device Registration
Each ASEAN member state retains regulatory authority over medical device registration. Manufacturers register with each member state’s regulatory authority.
Under the EU Medical Device Regulation, the EU legal manufacturer or authorized representative is required to register each medical device with the national competent authority in certain member states. The new EU 2017/745 Regulation is much more directive. As part of the regulation, a single database, called Eudamed, that includes the following systems will be implemented:
- Registration of devices
- Unique device identification database
- Registration of economic operators
- Notified bodies and on certificates
- Clinical investigations
- Vigilance and postmarket surveillance
- Market surveillance
Of note, both the ASEAN MDD and EU regulations provide for exemptions for custom-made devices.
Conformity Assessment
The ASEAN MDD requires manufacturers to have medical devices assessed by each member state in which they market the device.
In the EU, once a device has been assessed by one notified body, it can be marketed throughout the EU. Significant structure has been developed to ensure agreement among member countries in how to consistently conduct these assessments. As described earlier, each risk level receives a different treatment.
Clinical Evidence
A device requires clinical evidence to demonstrate conformance with certain EPs/GSPRs. Clinical evidence comes from the critical evaluation of clinical data, which in turn is generated from clinical investigations or review of scientific literature (Figure 2).
Clinical evidence comes from the critical evaluation of clinical data, which in turn is generated from clinical investigations or literature reviews
The ASEAN MDD requires manufacturers to conduct clinical evaluations and investigations (depending on risk category) for each member state where the device will be marketed. The EU works as one market, requiring manufacturers to have sufficient clinical evidence to support the intended use of their medical devices. The new EU 2017/745 Regulation establishes a single system for the oversight of clinical investigations across the EU.
Labeling
Both the ASEAN MDD and EU 2017/745 Regulation address device labeling and use of symbols. The EU regulation requires manufacturers to deliver medical devices with accompanying information written in official EU languages, as determined by the member states. The ASEAN MDD states that members states may set the requirements for having the label of a medical device in their national languages. Differences in each ASEAN member state’s claims for device labeling may create additional requirements for medical device manufacturers.
AAMI recognizes the need to have internationally harmonized standards on label content and use symbols to overcome language differences. To address these concerns, plans exist to revise ISO 15223-1:2016. It is important that different countries do not use different symbols to represent the same thing or, even more problematic, that they do not use the same symbol to represent different things. Global acceptance of symbols will require addressing cultural differences that affect symbol interpretation and even what constitutes a symbol (e.g., a word or acronym in a square box).
Market Surveillance
Both the ASEAN MDD and EU 2017/745 Regulation recognize the importance of market surveillance. The ASEAN MDD requires member states to take steps to record and, where required, evaluate malfunctions, deteriorations, technical or medical issues, or labeling inadequacies. The EU 2017/745 Regulation requires CAMDs to perform checks, devise annual surveillance activity plans, and coordinate surveillance activities across member states.
The ASEAN’s MDD includes less specificity than the EU 2017/745 Regulation. As a gross measure, the EU 2017/745 is 175 pages in length, whereas the ASEAN MDD is 99 pages. In part, this is a result of the ASEAN and EU differing in their systematic application of these regulations and directives, degree of implementation, and compliance. This difference also may correlate with the regional safety and effectiveness of medical devices.
Source: 7th ASEAN Medical Device Committee Annual Meeting in Bangkok, Thailand, in December 2018. Regulation (EU) 2017/745. The ASEAN Medical Device Directive. BI&T
