Medical Device Regulation in China

Qin Sun explains the system of medical device regulation in China and compares it with the systems in the US and the EU.

Qin Sun is a senior officer and deputy section chief at the Shanghai Food & Drug Administration's Department of Medical Devices.

This article is the first of two on the regulation of medical devices in China. The first article examines the existing system of medical device regulation in China and compares and contrasts it with the systems in place in the United States (US) and the European Union (EU). The second article, which is due to appear in the November/December 2006 issue of RAJ Devices, suggests several areas where US and EU practice and experience might be adopted for use in China as it continues to develop its medical device regulatory system.

Around 1.3 billion people - almost one quarter of the world's population - live in China and so the potential demand for medical devices is huge. With large amounts of healthcare products being manufactured, distributed and used, the country needs a sound regulatory system to guarantee product safety and the safety of its citizens. China issued its core regulation for the control of medical devices and related provisions for medical device classification, registration and distribution, etc in 2000 (see Diagram 1). A three-tier institutional structure is responsible for medical device administration (see Diagram 2), and this is conducted via a traditional model of bureaucracy. All of these efforts to some extent regulate the device business and serve to improve the quality of domestic products. However, regulatory control of medical devices is still loose and ineffective, as evidenced by the large amount of counterfeit and poor quality devices existing in the Chinese market and in user facilities throughout the country. Recent examples include:

• in 2003-4, the Chinese government declaring that all domestic blood bags did not meet performance standard requirements and therefore were unsafe; and
• in 2004-6, hundreds of adverse events being reported by users of injectable polyacrylamide hydrogel for breast implants.

The current regulatory framework

The promulgation in 2000 of the Regulation for Administration and Supervision of Medical Devices (Regulation 2000) and its related provisions was a milestone in China's device regulatory history. The Chinese government had set up a basic regulatory framework for the administration of medical devices, establishing the market entry for safe and effective devices. However, the system is complex and, among other things, it varies considerably from what are already - or are becoming - international norms. In addition, there is little efficient postmarket control. There is therefore a need for reform of device regulation that will address all areas of concern, from access to high quality, affordable products, through to their safe and appropriate use and disposal.

Scope and definition

The definition of what constitutes a medical device in China as set out in Regulation 2000 is essentially identical to that in the European Medical Devices Directive (MDD). China's Medical Device Catalogue 2003 provides examples of products in 41 specialist groups. At the broadest level, there are two groups of products: electrical medical devices and non-electrical medical devices.

Notwithstanding the above, there are ambiguities when it comes to defining the scope of medical devices in China. For historical reasons, some conflict exists between the legal definition and the government's interpretation of what a medical device is. For example, glasses, prostheses and wheelchairs and other instruments for the alleviation or compensation of handicap, are not regulated as medical devices in China although they obviously fit the legal definition of medical devices. Moreover, the current regulatory framework gives rise to much controversy in defining whether in vitro diagnostics (IVDs), human plasma derivatives, human tissues and combination products are medical devices or medicines. This ambiguity in demarcating drugs and devices has become one of the obstacles in establishing an effective regulatory regime in China.

Risk-based classification

Classification is an important feature in device regulation, because all further regulatory activities (both pre-market and postmarket) are based on the class of device. As in many jurisdictions, once a product has been defined as a device, it is classified according to its inherent risks.

According to Regulation 2000, the Provisions on Medical Device Classification and the Catalogue of Medical Device Products Classification, all regulated devices are divided into three classes. Classification is essentially based on three main rules: the duration of contact with a person; degree of invasiveness; and the anatomy affected by the use of the device.

Class I devices are those low-risk and simple products, such as some surgical instruments, tongue depressors, bandages etc, whose safety and effectiveness can be controlled by general administrative requirements. Class II devices have medium risks and certain technological requirements, such as ultrasonic diagnosis machines, clinical laboratory equipment and surgical microscopes, which need relatively higher standards to ensure their safety and effectiveness. Class III devices, which have the highest inherent risks and most sophisticated technology, such as implantable and life-support products, need the strictest administrative criteria, since these products can be life-saving and life-sustaining.

There are problems, however. Firstly, there are conflicts between the classification rule and the catalogue. Some devices are listed as Class III in the catalogue, whereas they should be regulated in a lower class according to the rule. Secondly, many more devices are deemed to be high-risk in China than in other jurisdictions. Under the Chinese classification regulations, more than 30% of devices are Class III, compared with only about 8-10% in the EU and the US. There have been increasing complaints from industry that the unreasonable classification causes enormous economic burden to manufacturers. Moreover, it has been argued by both industry and government that this inappropriate proportion of Class III devices is the main reason for the inefficiencies and ineffectiveness of the current Chinese regime.

Thirdly, the current classification regulation is too rigid to meet the rapid development in medical technology. There is the lack of a route for reclassification, when device-related incidents happen or medical technology improves. Lastly, there are still some difficult cases to be classified without any ambiguity. Therefore, specific guidance documents on the use of the rules and the catalogue have to be issued by the government.

Pre-market approval: product registration and manufacturer licence

Before being produced and distributed, all medical devices must be registered by the manufacturer or importer. Domestic devices must be registered with the three-tiered administrative system according to their class; imported devices must be registered with the central department, ie the Shanghai Food and Drug Administration (SFDA).

Regulation 2000 also defines where the responsibility lies for device control. The registration of Class I devices is carried out by district food and drug regulatory authorities; the registration of Class II devices is done by provincial food and drug regulatory authorities; and the registration of class III devices is the responsibility of the SFDA. Moreover, clinical investigation or verification must be carried out for some Class II and all Class III devices before they are put into production. Clinical investigation or verification must be carried out according to the Provisions on Medical Device Clinical Trials.

The term of validity for the registration certificate has been set as four years, and manufacturers must apply for re-registration up to six months before their certificates expire.

There are special requirements for some manufacturers. Domestic manufacturers must obtain a device manufacturing enterprise licence before they can produce devices. Importers of Class II and III devices must obtain a device distributing enterprise licence from the provincial or central regulatory authorities. According to the Medical Device Manufacturing Enterprise Supervision & Administration Method, the requirements for manufacturers are also based on the class of product. For Class I product manufacturers, the requirement is to submit the file record to the local authorities, which is the lowest criteria. Manufacturers planning to produce Class II or III devices must satisfy a series of conditions, including manufacturing facilities, qualified experts and good quality systems.

There are additional special requirements for manufacturers of certain products. For instance, manufacturers of sterile, single-used and invasive devices such as syringes, wound dressings, blood bags, and artificial joints must meet additional cleaning and sanitation requirements of their factories and environment.

Pre-market approval is a vital step in ensuring safe devices and quality-assured production. However, the pre-market regime has its problems. Firstly, it has been argued since the promulgation of Regulation 2000 that it is illogical to allocate the pre-market assessment of Class I and II devices to different local authorities. Medical device technology is widely interdisciplinary so that various qualified experts are needed in dealing with different types of technical problems. Some local authorities have too little expertise for such a high and wide level of detail.

Secondly, the current regulation framework is too simple and actually cannot cover a large number of different products. There are no technical requirements in the regulation or related provisions. For example, the Regulation 2000 and Provisions on Medical Devices Registration are enabling legislation and only provide some general principles for central and local authorities' work. The ambiguity of the current regulations allow too much discretionary power in the implementation of the legislation; consequently the safety and effectiveness of a product may be judged according to an administrator's limited knowledge and opinion.

Developments in postmarket surveillance

The Chinese government has been paying more attention than ever before to medical device postmarket surveillance because of a number of device-related adverse incidents in hospitals or other user facilities. The government realised that pre-market approval cannot eliminate all the risks relating to a medical product, especially in those Class III and implantable, life sustaining devices. There is, therefore, an urgent need to establish a postmarket surveillance system which deals mainly with device-related adverse events and supervises devices that are in use.

However, due to its limited experience with, and its relatively short history of, device regulation, the Chinese government does not have any regulations for postmarket surveillance. After a serious adverse event relating to a pacemaker in 2001, a temporary normative document was issued requiring that all device-related death and injuries be reported to local authorities within 15 days. Further to this, the government is conducting a regulatory investigation into further legislation of postmarket surveillance. This would include an adverse event reporting system and vigilance/monitoring system. Enforcement of adverse events reporting is being done on a pilot basis in some major cities, including Beijing, Shanghai and Guangzhou.

The government is also in the process of developing quality system requirements for manufacturers (good manufacturing practice), good clinical practice (GCP) requirements, a national standards system and advertising requirements.

Medical device administrative structure

Before 1996, the administration of medical devices was the responsibility of the State Pharmaceutical Administration of China (SPAC). In 1997, a new department - the State Drug Administration of China (SDA) - was established to fulfil the missions of both policy making and policy implementation. Six years later, the SDA was replaced by the State Food and Drug Administration (SFDA) with a new mission of food administration authorised directly by State Council.

Since 1997, the State Council has been building a medical device administration system. It employs about 8,000 employees, who work in state and local regulatory authorities. State regulatory authorities are directly controlled by State Council, while the local regulatory authorities work under the supervision of the state regulatory authority. Vertically, China has a three-tier structure for device administration and management: state, provincial and county level. In each tier, a horizontal administrative framework has been established as well (see Diagram 2).

Despite the fact that the central government has established a wide and multi-level administrative framework for devices, the system is arguably still highly centralised, with fundamental decisions all taken from the centre. In practice, the Department of Medical Devices (with just 12 officials and very little outside scientific support) in the state authority (ie, the SFDA) has all the responsibility for policy making and for drafting and implementing legislation. It is responsible for:

• drafting laws and regulations on device administration, relevant device standards and manufacturing practice; and
• controlling the quality of devices at the manufacturer, distributor and medical institution level.

One criticism is that the central setting is problematic in that it bestows too heavy a responsibility to the Department of Medical Devices. Moreover, the department lacks a sensible administrative policy-making mechanism. As a consequence, a number of policies made by the central authority are not feasible or can cause conflicts during implementation. On the other hand, a large number of local officials only take responsibility for a small part of policy implementation, the chief one of which is the registration of lower-risk devices.

Policy making and policy implementation are conducted according to the legal basis of “enabling act” and “administrative procedure law”. Nonetheless, this legal basis for device administration in China is inadequate and sometime controversial, and can lead to inappropriate administration.

Firstly, according to the enabling law, two departments have the same functions (pre-market registration) in the administration of certain types of devices. Secondly, due to the lack of effective procedure law for administration, officials often have too much discretionary power with regard to policy implementation. Thirdly, there is not an appropriate control mechanism to ensure the proper separation of powers. Moreover, due to the lack of proper administrative coordination between different departments, the situation can become worse.

A comparative analysis of China, the US and the EU

The US and the EU have had leading roles in the development and harmonisation of medical device regulation. Moreover, the US Food, Drug & Cosmetics Act (FDCA) and the MDD in the EU introduced several key concepts such as device classification, good manufacturing practice (GMP), vigilance etc, which were adopted by the Global Harmonization Task Force and other countries. It is instructive, thus, to make a comparison between the Chinese and EU/US regulatory systems to present some valuable experiences for regulatory reform in China.

Comparing three regulatory systems, it is not surprising to find two different approaches (pharmaceutical and engineering). In the US, the medical device regulation is a subsidiary part of the pharmaceutical law; as a result some device requirements are derived from a pharmaceutical approach. On the other hand, the European directive and the Chinese regulation were conceived and drafted independently by adopting an engineering approach. In general, the US regime is more stringent than that of the EU and China.

Scope and definition

There are also differences in the definition and scope of medical devices in the three jurisdictions. The legal definitions of medical devices are described in a general sense and usually use abstract terms. Therefore, governments provide a set of guidance documents to make further interpretations to help administrators and industry judge whether or not a product falls within the definition. For example, the FDCA has a relatively narrow definition of medical device but the FDA has given a broad interpretation to it. It has claimed jurisdiction and classified a number of products for disabled persons, which were originally not included in the legal definition. The clear and reasonable guidance documents for the interpretation of definition are an effective redress to define the scope of medical devices.

The definition in Chinese regulation is almost the same as that in the MDD. Despite this, there are always conflicts and ambiguities between the legal definition and government's interpretations. As already mentioned, IVDs and products for handicap alleviation or compensation are two notable examples. According to the definition in Regulation 2000, products which have the intended objectives of “diagnosis of disease … alleviation of or compensation for … handicap conditions…” are medical devices. It seems obvious, therefore, that IVD and products such as wheelchairs or crutches fall inside the definition and should be regulated in accordance with the regulatory regime for devices. Subsequent normative documents issued by the government, however, state that products with the intended purposes of handicap alleviation or compensation are not devices but general consumer products, and that IVDs are regarded as drugs and subject to pharmaceutical law.

It is also not always clear how the government decides whether certain types of products, eg combination products, are medical devices. Unlike in the US, for example, there is no legal document in the Chinese regime for the management of combination products. The same problem exists with other products, especially those involving high technology, such as human plasma derivatives, human tissues and so on.

Although the Chinese definition of a device is nearly the same as that in the MDD and quite similar to that in the FDCA, the ambiguity in defining the scope of devices in the Chinese regime is a serious obstacle to achieving efficient and effective management. Government administrators and manufacturers have complained about the uncertainty in judging whether specific products are subject to device regulation. Moreover, the differences in interpretation between the Chinese government and the EU/US cause trade barriers and increase the burden on the manufacturers. This inefficient mechanism also leads to delays in the innovation of health technology.

Classification

While the concept of risk-based classification in medical device regulation exists in the US, the EU and China, there are major differences between the three systems.

Firstly, the European directives introduced a different classification regulation which divides all products into four classes: low risk, medium low, medium high and high risk. The Chinese and US regulation both have a three-tier classification: low, medium and high risk. It has been argued that the European approach of four level classifications is more sensible and helpful for the next step of risk management in pre-market control.

Secondly, the FDA set its classification system with the cooperation of classification panels, which constituted a large number of scientists, doctors and other academics. They established a device database with each device given a specific class. The idea of classification panels was not accepted by EU and Chinese regulators, who instead adopted a classification rule which allows manufacturers and regulators to determine under which class a device comes.

Thirdly, in addition to the classification rule, the Chinese government set up a Classification Catalogue (see above) to guide officers and industry. Lastly, and as already mentioned, far more devices are in Class III in China than in either the EU or the US.

GMP requirements

Manufacturer compliance with quality assurance standards is required by all three administrations; however, there are different quality system requirements in the three sets of regulations.

In the US, GMP compliance is required by the Quality System Regulation. In the EU, it is part of the product approval process and is supported by a well-established standards system. GMP in China lacks legal support, in terms of both GMP regulations and an effective standards framework. China has adopted some international standards - such as ISO 9001 on quality systems in general and ISO 13485 and ISO 13488 on medical device quality systems - as its national standards and it uses these standards for pre-market approval of enterprise licences. In addition, inspection or certification of the quality system is becoming a condition of approval. However, the requirements of quality system in the Chinese regime are not systematic and they lack clear legal basis.

Pre-market controls

The use of standards

Compliance with voluntary product standards is becoming a preferred means of demonstrating compliance with regulatory systems, especially in the EU. The MDD gave a prominence to the principle of reference to standards and has probably been the main user of this principle; the ‘deemed to satisfy’ condition offered by harmonised standards is a key feature.

In China, manufacturers applying for registration of medical devices should submit technical standards to the regulatory authority and the devices should meet the requirements of technical standards. However, the Chinese government has not promulgated enough national or professional standards for the industry to comply with and some of the current standards lag far behind the updated international requirements. As a result, a special kind of standard called “registration standard” has come into being. When a manufacturer intends to apply for registration of a device, the specific registration standard should be created and submitted to the government. This kind of standard has no legal basis.

Different routes to product registration

With the MDD and the FDCA, the EU and US systems introduced some degree of industry choice in terms of routes to product registration. The requirements for most Class I devices are streamlined in that they are not subject to pre-market approval but exempted from complicated assessment in both the EU and the US. Moreover, the MDD provides a more flexible regime by using quality system with product design as an important alternative. Different routes of conformity assessments can be chosen by manufacturers when they intend to apply for assessment of a product.

The situation in China is not the same. All devices have to be registered by their manufacturers, including Class I products such as the simplest tongue depressor or stethoscope. Although Regulation 2000 requires that devices are administrated based on their class, there is no visible difference between the requirements for Class II and Class I devices. Further to this, the enterprise licence for device production is required when applying for production registration. Requirements for device registration are rigid and the application process is usually costly and time-consuming.

Moreover, a further significant difference in the area of product registration is in the nature of the permission to market medical devices. In the EU, no formal approval is given; instead, manufacturers affix the CE marking on their products, which have gone through the appropriate conformity assessment and obtained certificates or reports from a notified body. In the US and China, formal approval for a specific device is issued by the government after document evaluation and appropriate site inspection.

The requirement of effectiveness

It is widely recognised that the feature of effectiveness is a key element in medical device regulation. However, this requirement is probably the least well understood aspect of the pre-market control process.

The US has a clear requirement on effectiveness that the effectiveness of a device is to be evidenced by well-controlled investigations, including clinical trials and verification. In the main texts of the EU directives, there is no mention of terms such as ‘effectiveness’ or ‘efficacy’; however, the requirements of effectiveness are expressed in the essential requirements of the MDD, where the performance and risk versus benefit assessment must be carried out by appropriate clinical investigation or verification. The US treats devices and drugs in a similar way, whereas the Europe has an engineering approach to devices by putting more concentration on laboratory tests and historical data. In the Chinese regulation, it is clearly required that all devices must be safe and effective to protect the public health; moreover, it requires that most Class II and III devices go through clinical trials to ensure their safety and effectiveness. The Chinese requirements on effectiveness, however, are criticised as unreasonable, over-regulated and burdensome to manufacturers.

Postmarket controls

Postmarket surveillance systems in the US and the EU are well established, although still evolving. In China, there is no regulation on postmarket controls, although the government recognises its important role in ensuring safe and effective devices. With the increasing emergence of device-related adverse events and the influence of GHTF, the Chinese government put postmarket controls onto its policy agenda and it has been working to develop provisions in this area for more than two years. Its policy investigation was made largely on the basis of current US and EU requirements. There is a proposal for an adverse event reporting regulation; regulators, however, are continuing to work on a clear definition of a reportable event and the methodology to be used in any postmarket surveillance system.