Many medical devices are not yet regulated in India, nor is there an official definition of a medical device. However, the Indian government intends to create a new national drug authority and has proposed the creation of a new medical device division within it. Up to this point, individual devices, such as disposable hypodermic needles and syringes, metered-dose inhalers, and other such devices, have had unique regulations. Other devices regulated in India in the past include diagnostic x-ray equipment, disposable perfusion sets, intrauterine devices, in vitro diagnostic kits for HIV, and sterilized sutures and ligatures. In some cases, devices have been categorized as drugs, meaning they fall under the purview of the Drug and Cosmetic Act (DCA).
In October 2005, 10 devices were classified as drugs in notification S.O. 1468(E) to bring them under the purview of DCA. On March 1, 2006, the drug controller general of India (DCGI) issued new medical device guidelines regulating the import and manufacture of these newly notified devices. The 10 selected medical devices are cardiac stents, drug-eluting stents, catheters, intraocular lenses, IV cannulae, bone cements, heart valves, scalp vein sets, orthopedic implants, and internal prosthetic replacements.
The new guidelines stipulate that all importers of these devices are required to apply for import licenses and to file product registrations with DCGI. The application must include such documentation as the master file, detailed product information, postmarket surveillance procedures, and safety and quality system standards for the device. The full documentation is according to Form 40, Schedule DI, and Schedule DII modified for devices. It consists of the following information:
- Applicant information: name, address, plant master file, local agent, and importer.
- Product information: proprietary or brand name, description, intended use and method of use, contraindications, device category, user manual, labels, storage conditions, standards, method of manufacture, and materials used.
- Regulatory status: proof of approval from FDA, a CE certificate, or proof of approval from other national regulatory entities; ISO/EN certification of the manufacturing facility; a list of countries where the product is sold, and if applicable, countries where the product has been withdrawn from the market (which must be accompanied by an explanation).
- For devices containing medicinal products: data on the safety, quality, and efficacy of the medicinal substance; data on device compatibility with medicinal products; clinical data; and research articles.
- For devices that have not been approved in the country of origin: reports of clinical trials, sales, and certificates of satisfactory use from medical specialists; details of product complaints.
- Postmarket surveillance: procedures for the distribution of records, complaint handling, adverse incident reporting, and product recall.
- Demonstration of conformity with product standards, safety, efficacy, and quality systems in country of origin.
The DCGI may also require testing locally or abroad. Expert committees are sometimes formed to evaluate specific categories of devices, developing evaluation benchmarks as well as the standards that the devices should meet.
Some additional licenses are also necessary. For some imported devices, the importer or agent must have a license to stock and sell the products. When a selected device is manufactured in India, a manufacturing license is required for the factory. The requirements for a manufacturing license include a GMP inspection, qualified staff, and an appropriate testing lab. If patented or proprietary drugs are being manufactured, proof must be furnished that they are being made according to the claims and conditions officially specified for the drug. An importer or agent must also have a manufacturing license in order to do any reprocessing or prepacking.
The 10 selected devices and any device without benchmark certification would first be evaluated by an expert committee, which would make a recommendation to the state licensing authority (SLA). If the recommendation was favorable, SLA, following a GMP inspection and verification of the recommendation, would forward the application to the Central Licensing Approval Authority.
All importers and manufacturers of these medical devices were required to file applications for the necessary licenses by April 30, 2006, which was later extended to June 30, 2006. The application fee is $1500 per factory and $1000 per product. In addition, any importer or retail seller of these devices must obtain the appropriate sales licenses from SLA one month after the deadline.
Last June, the Indian government issued a list of clarifications to the application guidelines in response to the many questions it had received. Those clarifications include the following information.
An applicant may register similar medical devices as a family, in which case the entire line of devices may be registered for a single registration fee. The products grouped together must have the same basic design, intended use, and effectiveness, but may vary in size and shape. For example, catheters made of the same materials and with the same therapeutic purpose may be registered as a family.
The plant master file required in part A of the import license application consists of the location and layout plan of the manufacturing site, overviews of the manufacturing process and quality control system, the conformity assessment system used, production capacity of the plant, and the details of the plant's approval or registration certificate issued by its country's regulatory authority.
If any processing of the product takes place in India—making, altering, finishing, packaging, labeling, or breaking up—the processor must be named under “Local Manufacturer” in part A.
The “Qualitative and Quantitative Particulars of the Constituent” section in part B requires not only the materials that make up the product, but also the standards they conform to and the system the manufacturer uses to assess their quality.
Generally, labeling that meets either Global Harmonization Task Force (GHTF) or ISO specifications will be accepted. However, manufacturers should consult the Indian Drug and Cosmetics Rules to make sure the current labeling is sufficient.
Although the guidelines require a guarantee that the product conforms to the manufacturer's quality and safety standards, the government has decided that because the same guarantee is also required at the time of import, it may be omitted from the import permit application form.
Price Controls. As part of a new pharmaceutical policy proposed by the Indian government, medical device manufacturers could face new price restrictions when selling to public-sector medical institutions. The proposed policy places expensive, critical medical devices under a differential pricing system to make them affordable to low-income patients. Manufacturers would also be required to engage in price negotiation when selling to any state-run hospitals, retail outlets, or health projects. These proposals come as part of an overall effort by the Indian government to implement further price controls on the medical industry. Critics of the proposed policy say it will do little to lower medical costs for most Indians, and that it may do more harm than good. Price controls may prompt companies to lower their R&D budgets or avoid entering the Indian market. Critics believe the restrictions could also lead to shortages of these products, increasing incentives for making counterfeit products. The safeguards the government implements to mitigate its price control policies' negative effects will be critical.
Hong Kong is legally a part of China, but its government functions independently in most matters. There are currently no product registration requirements for medical devices imported into or sold in Hong Kong. However, in 2003, Hong Kong's Department of Health launched the Medical Device Administrative Control System (MDACS) to lay the groundwork for the transition to a mandatory regulatory regime. The first phase of the MDACS, which began November 26, 2004, permitted medical device companies to voluntarily list their Class IV (high-risk) medical devices. The second phase, implemented a year later, allowed medical device companies to voluntarily list their Class II and Class III (medium-risk) medical devices. The devices covered include those used in healthcare facilities as well as those sold to consumers.
The Medical Device Control Office (MDCO) has recommended that manufacturers of medium- and high-risk medical devices apply to list their products, and it has posted a series of guidance notes on its Web site (www.mdco.gov.hk) to familiarize companies with the MDACS. These notes provide an overview of the MDACS system, guidance for listing Class II, III, and IV medical devices, and guidance on adverse-event reporting.
MDCO is also planning to introduce a conformity assessment framework to improve the quality management of medical devices in Hong Kong. It has proposed two documents for implementation: “Conformity Assessment Framework” (GN-04) and “Principles of Conformity Assessment for Medical Devices” (TR-001). The former is a set of guidance notes on the matter, while the latter is a technical reference.
Assessment would be conducted by a conformity assessment body (CAB) recognized by MDCO under MDACS. The purpose of conformity assessment is to demonstrate that a medical device is safe and performs as intended by the manufacturer, and that it conforms to the principles of safety and performance for medical devices outlined in GN-01, “Overview of the Medical Device Administrative Control System.”
Conformity assessment would be conducted before and after a medical device enters the market to provide information on safety, performance, risks, and benefits in order to maintain public confidence. It is the medical device manufacturer's responsibility to meet conformity requirements, the assessment of which would be conducted by an independent certification body recognized by the government and also based in Hong Kong. But the government would ultimately determine whether the relevant MDACS requirements are fulfilled. Medical device manufacturers could eschew Hong Kong's certification process if their devices have already been certified by one of the founding GHTF members (Australia, Canada, the European Union, Japan, and the United States).
The proposed documents provide guidance on the principles of conformity assessment for medical devices and recognize that assessment should be more rigorous for high-risk medical devices. Class I medical devices do not have to be included, but medical device manufacturers that want to become listed manufacturers under MDACS should include them in conformity assessment.
Part of the assessment would require the device manufacturer to establish a subset of technical documentation to be held or submitted as required by the class of the device. The CAB would determine the adequacy of the documented evidence through a review of details laid out in the technical document regarding conformity assessment (TR-001).
A briefing session on the two proposed documents was held August 10, 2006. According to MDCO, a proposal on the statutory regulation of medical devices will be drafted this year.
Standards for testing device safety are high priorities for countries that have recently developed regulatory framework.
South Korea's move toward device regulation started with the Medical Devices Act (MDA), which was developed in 2003 and went into effect May 30, 2004. However, it is still in a transition period—full enforcement of the MDA begins May 30, 2007. The MDA provides for the independent regulation and safety management of medical devices and aims to harmonize Korea's medical device regulations with international standards. The Korea Food and Drug Administration (KFDA), the national regulatory authority, is now considering dividing itself into two agencies—one to cover food safety and the other to cover drug and device administration. KFDA has also considered expanding the number of device classifications from the current 1000 to a new total of about 2000 more-detailed classifications.
The MDA introduced new postmarket surveillance initiatives, including tracking, adverse-event reporting, reexamination, and reevaluation. KFDA may require tracking for certain devices, such as implants or life-sustaining equipment used outside of hospitals or other medical institutions. The MDA requires safety information and timely reporting of any adverse event, such as death, serious injury, or disability.
Reexamination is done on new or orphan devices that do not yet have established safety or effectiveness records at the time of approval. KFDA may gather data on the device in the first several years to ensure that it is safe and effective enough to merit a permanent product approval. KFDA may also call for reevaluation of existing medical devices to improve them with updated technology and standards.
Specific guidelines for the implementation of these initiatives are still being developed. KFDA has recently been consulting with the medical device industry about periodic retesting of devices for KGMP certification, including tests such as biocompatibility and sterility. In March 2006, KFDA issued a pricing regulation for medical devices that allows for a separate evaluation process for a new product registering a new function.
Taiwan has required manufacturers to be fully compliant with good manufacturing practices, including device inspection techniques, since 2004.
In June 2000, the Taiwanese Bureau of Pharmaceutical Affairs (BPA) of the Department of Health (DOH) reclassified its medical device categories and began requiring all medical devices to be registered prior to importation. BPA allowed a 5-year transition period, with implementation effective June 20, 2005. BPA's decision to require even Class I devices to be registered was unpopular. Consequently, the organization revised the rules in March 2006, allowing for simplified Class I registration for imported medical devices. Simplified Class II and III device submissions are only permitted if the device has marketing approval from the United States (a certificate for foreign government [CFG] or 510(k) letter) and the European Union (free sale certificate from health authority or comparable letter).
In Vitro Devices (IVDs). Although IVDs are also classified as medical devices and must follow the same registration guidelines, they also have their own specific set of regulations. The IVD product registration guidelines were released in July 2003, and a requirement for quality system documentation was issued in February 2004. As of December 2005, all IVDs must complete product registration before products can be imported. Infectious-disease reagents were reclassified from pharmaceuticals to IVD products in February 2003. Last year, BPA stipulated that local clinical trial evaluations for infectious-disease reagents must be submitted to the Center for Drug Evaluation.
Good Manufacturing Practices. GMP compliance has been required since 1999 and is based on ISO 13485. Full compliance became mandatory in 2004. All manufacturers of imported medical devices must submit a quality system documentation application. U.S. and European companies are exempt if they have their establishment inspection report, CFG, and an ISO 13485 or EN 46001 certificate. DOH recognized five additional EU notified bodies in February 2006: KEMA (The Netherlands), SGS (UK), AMTAC (UK), MEDCERT (Germany), and DGM (Denmark). These five notified bodies supplement the six already recognized by DOH.
Medical devices do not have to be registered in Singapore, except for contact lens products, radiation-emitting devices, and condoms, which come under statutory control through provisions of the Contact Lens Practitioners Act, the Radiation Protection Act, and the Medicine Act, respectively. The Health Sciences Authority (HSA) is the regulatory authority, and the Center for Medical Device Regulation (CMDR) is responsible for regulating medical devices in Singapore.
Over the past few years, CMDR has implemented several voluntary regulatory initiatives for medical devices to keep up with global trends while maintaining the quality, safety, and efficacy of medical devices in Singapore. Devices are classified into four categories: I (low risk), IIa and IIb (medium risk), and III (high risk).
The Voluntary Product Registration Scheme, launched in 2002, encourages local authorized representatives of medical device companies to register their products with CMDR. The project targets medium- and high-risk medical devices in Classes IIa, IIb, and III, and IVDs in List A, List B, and self-testing categories. The voluntary registration constitutes a premarket application made to HSA before the device is placed on the Singapore market. Evidence of the safety and effectiveness of any Class IIa, IIb, or III device or List A, B, or self-test IVD should be submitted to HSA.
The Singapore Medical Device Register is a database of medical devices that are imported into or exported from Singapore. Manufacturers should submit information on the quality, safety, and efficacy of their devices (though listing in the register is voluntary). CMDR first reviews the submitted information using standards that satisfy the regulatory requirements of developed countries in making its premarket assessment. The objective is for hospitals and clinics to use the register to purchase listed devices that meet those regulatory standards. CMDR will also use its database to monitor the postmarketing activities of medical device companies.
CMDR and HSA have developed the Medical Device Information & Communication ([email protected]) system. MEDICS is a Web-based system that provides an electronic environment for interaction between medical device establishments and the regulatory authority. Currently, users can access several key documents through MEDICS, including the establishment license application, the market clearance application for higher-risk devices, the notification of export-only unregistered medical devices, and more. More information is available at www.hsa.gov.sg.
The Malaysian government decided in February 2005 that it would begin regulating medical devices to harmonize its regulations and standards with those of other Asian and industrialized countries. There are currently no product registration requirements for imported medical devices in Malaysia. The only exceptions are radiation-emitting devices such as x-ray equipment, which are subject to prepurchase evaluation by the Malaysian Ministry of Health and also require a permit from the Atomic Energy Licensing Board.
Malaysia made its first step toward a medical device regulatory regime with the development of the Voluntary Registration Scheme for Medical Devices Establishments (MeDVER), a voluntary registration system launched by the Ministry of Health in January 2006. MeDVER is a Web-based system, and all the registration steps can be completed online. Medical device establishments participating in MeDVER must submit information about the establishment, the person responsible for the establishment (e.g., the CEO, managing director, etc.), the devices, postmarket requirements, and an application declaration.
Medical device establishments can include manufacturers, exporters, importers, distributors, and vendors of medical devices. Although registration is voluntary, all medical device establishments are encouraged to participate. Participation, however, does not constitute approval of the establishment or its devices by the Ministry of Health. The four objectives of MeDVER are:
- To familiarize medical device companies with the registration process.
- To gauge the readiness of device companies to conform to regulatory requirements.
- To prepare medical device companies for a smooth transition into the regulatory phase before full enforcement of medical device regulation goes into effect.
- To obtain a profile of the Malaysian medical device industry. The Malaysian government plans to begin requiring product registration for all medical devices in 2007.
Many Asian countries have just begun developing new or more-rigorous regulations for medical devices. The next few years will be crucial as more nations create regulatory authorities to oversee the industry. As standards and qualifications are steadily being developed and amended, manufacturers need to keep up-to-date with the evolving regulatory climate in these countries.
Ames Gross is president and founder of Pacific Bridge Medical (Bethesda, MD) and can be contacted at [email protected].