In today’s global recession, innovation, creativity and resourcefulness are essential. Using these tools to determine the appropriate regulatory strategy for your medical device could decide the success or failure of your product in Asia. This article provides the most recent regulatory updates in Japan, China and India to help gain entry to those markets.
Japan
MHLW and Increased Fees
Japan, the second largest medical device market in the world, can also be one of the most difficult to penetrate. Strict regulations and a highly bureaucratic government have led to medical device approval lags. Japan’s Ministry of Health, Labor, and Welfare (MHLW) is working to address this lag issue, including hiring additional staff and increasing the budget.
Part of MHLW’s plan calls for increasing the number of Pharmaceuticals and Medical Devices Agency (PMDA) medical device reviewers from the current 35 to 104 by 2013. To help pay for additional reviewers, the government fees for reviewing medical device applications (“Shonin” applications) significantly increased in April 2009.
Previously, the lowest possible fee for a Class II device that both conformed to technical standards and did not require clinical trials was ¥386,700 or approximately $3,900 ( US). Now, the fee for the same device will be ¥445,900 ($4,500). Fees for devices that did not match technical standards were previously ¥1,286,100 ($12,900), and will now range from ¥1,511,700 ($15,300) to ¥2,457,200 ($25,000), depending upon their specific classification and degree of novelty.
The steepest fee increase will be for new devices supported by clinical trial data. Previously, such applications cost ¥3,849,000 to review ($39,000). Now, the cost will range from ¥4,485,700 ($45,500) to as much as ¥9,470,000 ($96,000), again based upon the classification and degree of novelty.
It should be noted that this fee increase does not apply to Class I devices, which only require notification. It also does not apply when a Class II device is submitted to a third party (Notified Body) for “Ninsho” approval. In that case, the third party sets the fee independently.
More Categories
According to PMDA’s plan, not only will fees increase, but more medical device categories will be added so the fee structure more closely matches those in other countries. In the current system, medical device review fees are determined by two factors: whether the application is supported by clinical trial data and whether the device conforms to the government’s technical standards for its type. Under the new system, fees will also vary based upon whether the device is Class II, Class III or Class IV and whether it is a novel, improved or “me-too” medical device.
After abolishing the me-too category under the Pharmaceutical Affairs Law (PAL) in 2005, the Japanese government decided to reinstate it to facilitate the review process. Me-too devices are those demonstrated to be equivalent to devices with current market approval in Japan.
Device review time should be reduced in the future. In addition to hiring more reviewers, PMDA will allocate specialized reviewers for each application category by 2011.
Evaluations and Review Times
PMDA plans to introduce an “initial evaluation system” for new medical devices that will enable the agency to perform a pre-application review of such testing data as biological safety, electrical safety and performance without waiting for clinical trial completion. This system should be implemented in stages beginning in 2010. PMDA also plans to improve the quality and quantity of agency consultations, including those for clinical trials, and clarification of review standards and procedures, which are often ambiguous in Japan.
Furthermore, PMDA is streamlining application document requirements for the me-too and improved product categories. The target review time for the me-too category is four months. The target review time for the improved products category is six months for devices that do not require clinical trial data and 10 months for those that do. PMDA is trying to shorten the approval process by setting application review time targets.
In Fiscal 2006, 23 new medical devices were approved, with a median total review time of 19.7 months. In Fiscal 2007, 26 new medical devices were approved and the median total review time decreased to 17.1 months. New medical devices do not include Class I or II devices or any devices that do not require technical standards or clinical data.
While working to shorten approval times, PMDA has continued its commitment to registered medical device and drug quality and safety. With increasing numbers of medical product applications each year, PMDA must inspect more facilities and documents in less time.
The number of paper audits to check conformity has increased dramatically in recent years. In Fiscal 2005, there was only one medical devices document conformity audit, but this number jumped to 175 in Fiscal 2006 and 540 in Fiscal 2007. The number of Good Manufacturing Practice (GMP) and Quality Management Systems (QMS) audits for medical devices has also increased. There were 94 medical product GMP/QMS audits in Fiscal 2005, with 39 on-site inspections. This number increased to 1,120 in Fiscal 2006, with 204 on-site inspections, and reached 1,998 in Fiscal 2007 with 246 on-site inspections.
GCP
In late 2008, MHLW released its slated 2009 Good Clinical Practice (GCP) standard revisions governing medical device clinical trials. The new medical device GCP rules have two measures allowing more subcontracting in clinical trials, which may reduce clinical trial costs in Japan somewhat.
The first change is regarding Institutional Review Boards (IRBs). Previously, medical institutions conducting clinical trials were obligated to set up and maintain their own internal IRBs, which can be expensive. The change will allow a medical institution’s director to designate an outside IRB to perform this task. The designated IRB must be part of a university, nonprofit company or independent government agency, not a for-profit company. To preserve IRB transparency while making this change, the rules also add new reporting requirements. IRBs must make their internal procedures, members’ names and summaries of meeting minutes publicly available.
The second change involves the physical handling of investigational products. Previously, those running the clinical trial had to ship investigational devices and drugs (including confirming receipt and quality management). Now, the trial sponsor can designate a third party to perform these tasks.
The new medical device GCP standards took effect on 1 April 2009. However, the new reporting requirements for IRBs will not take effect until 1 April 2010.
China
Improving Medical Device Regulation
As the world economy has fallen into recession, a number of export-dependent industries in China have been hit hard. However, the medical device industry in China has not yet been significantly affected by this slump, and continues to grow.
Despite the slowdown in China today, the medical device market there is now a $7.5 billion industry and growing rapidly. Government purchasing of medical devices, both domestic and foreign, is also increasing at an exponential rate. To further develop its nascent rural healthcare infrastructure, the Chinese government has allocated 8.27 billion RMB (about $1.21 billion) merely for purchasing medical devices for the New Rural Cooperation Medical Program between 2008 and 2010.
Focusing on the growing medical device market, the China government has also issued new regulations to ensure quality and safety. During a national meeting on 14 January 2009, the State Food and Drug Administration (SFDA) laid out plans for the year for improving the regulation of medical devices. Improvements to medical device supervision and administration include: establishing standards and a legal system for medical devices; completing a medical device testing system; developing a medical device technical evaluation system; and enhancing medical device safety.
To address the first item, SFDA plans to upgrade Regulations for the Supervision and Administration of Medical Devices from a regulation to a State Council-issued law. In addition, the agency plans to revise Provisions on Medical Device Registration, Medical Device GMP, and Provisions on Medical Device Recall. Another proposal is to form a national committee for medical device standardization that will re-examine biological medical device registration standards.
For the second item — completing a medical device testing system — SFDA-affiliated testing centers would play leading roles and be supported by other qualified testing facilities affiliated with major universities or academic research institutions. To enhance testing centers’ overall capabilities, SFDA would implement more macroeconomic regulation and government subsidies to fill in the gaps of testing items or categories.
To enable development of a medical device technical evaluation system, SFDA would improve technical evaluation guidance and Good Clinical Practices (GCPs) for medical devices. The agency also plans to develop a comprehensive mechanism for evaluating and approving drug-device combination products and to strengthen IVD registration regulations.
For the fourth item — improving medical device safety — SFDA plans to speed up medical device classification and nomenclature, improve the medical device classification catalog and enforce existing medical device nomenclature regulations. Other plans include developing and implementing medical device electronic coding and strengthening adverse event monitoring supervision and regulation and device manufacturing and distribution.
Medical Device Review
SFDA recently held a conference in Guangzhou to discuss ways to improve the medical device technical evaluation process. Attendees included key officials from SFDA, its Department of Medical Devices and Medical Device Evaluation Center, and representatives from China’s 10 national medical device testing centers. Attendees heard reports from these centers and discussed current challenges and future development goals.
SFDA’s 10 national testing centers are accredited by the China National Accreditation Committee for Laboratories (CNACL) and the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ). They are responsible for product quality supervision, testing and evaluation, as well as maintaining technical standards for medical devices. The 10 centers are:
- Beijing Center for Medical Device Quality Supervision and Testing
- Medical Device Quality Supervision and Testing Center of Peking University ( Beijing)
- Center for Medical Devices – National Institute for the Control of Pharmaceutical — Biological Products ( Beijing)
- Shanghai Center for Medical Equipment Quality Supervision and Testing
- Tianjin Medical Instrumentation Inspection Center
- Wuhan Quality Supervision and Testing Center for Medical Devices
- Jinan Quality Supervision and Inspection Center for Medical Devices
- Shenyang Center for Medical Equipment Quality Supervision and Testing
- Guangzhou Quality Supervision and Inspection Center for Medical Instruments
- Hangzhou Center for Medical Equipment Quality Supervision and Testing
These national testing centers play a key role in the medical device registration process, and their capabilities have developed quickly in recent years. With the medical device industry’s rapid growth, however, the centers have been hard-pressed to keep up with increasing demand. As SFDA has tightened regulations and raised medical device registration standards, the centers have had to perform significantly more tests more thoroughly. Current testing facilities have insufficient resources to meet these requirements efficiently, prompting industry complaints about the slow registration process. Therefore, the Chinese government is seeking to improve the testing centers and the technical evaluation process.
In coming years, the centers are to focus on expanding current testing categories, improving the efficiency of technical support, providing more-accurate data, strengthening registration sample testing, improving personnel expertise and bringing testing quality up to international levels. Additionally, the mechanism for suspending and disqualifying testing centers will be strengthened and technical exchanges among testing centers will increase.
SFDA has also made efforts to develop smaller provincial and local medical devices testing centers. To date, more than 30 provincial and local testing centers have received accreditation.
Provincial testing centers usually handle domestic Class I and II medical devices in conjunction with provincial food and drug administration product review. National testing centers, on the other hand, usually test devices are under review by SFDA, such as domestic Class III devices and all imported medical devices. Provincial testing centers without the resources to conduct certain tests may forward those tests to a national testing center. Increasing the number of qualified provincial testing centers should lighten the load on national centers, allowing them to speed up the registration process for imported and high-risk domestic medical devices.
GCP
Increasing controls in China reflect the government’s strong interest in regulating the quality of clinical trials. Clinical research in China started late by international standards and there has been concern over the wide variation in clinical research quality among medical institutions. In upgrading government certification for clinical trial organizations, the Chinese government hopes to give applicants for new medical devices more confidence in the quality of the research institutions they choose. At the same time, the new regulations will push clinical research institutions to improve their facilities, personnel and quality assurance while lowering risks for clinical trial participants.
SFDA’s Department of Medical Devices recently held a meeting in Hefei, Anhui province, to discuss the structure and content of the latest draft of Good Clinical Practice (GCP) for Medical Devices (interim). This upgraded version of the Provisions on Clinical Trials for Medical Devices will bring Chinese GCP more in accordance with international standards. The new draft covers clinical validation more thoroughly, whereas the existing provisions, which took effect in April 2004, focus more on clinical trial logistics. They provide guidelines for subject rights protection, clinical trial plans and principles, medical institutions and personnel conducting clinical trials, clinical trial reports, etc.
Attendees at this meeting included officials from SFDA, the National Drug Evaluation Center and the Medical Device Evaluation Center, as well as representatives from medical device manufacturers and the China Association for Medical Devices Industry. Wang Lanming, deputy director of SFDA’s Department of Medical Devices, said in his keynote speech that drafting the new medical device GCP is one of SFDA’s key ongoing projects. In its revisions, the agency is focusing on strengthening management of technical aspects of medical device clinical trials as well as establishing a quick and effective mechanism to coordinate clinical trials with medical device registration.
India
Medical Devices Will Require Approval
India’s growing medical device market has prompted many multinational companies to open local offices in the country. In 2007 alone, more than 25 foreign medical device companies such as Boston Scientific, Medtronic, Abbott and DePuy received licenses to import medical devices through their local subsidiaries in India. Market growth can also be seen in the dramatic increase in medical device patents.
India’s government is working on a comprehensive regulatory framework for the medical device sector, which has lacked a formal regulatory system for many years. Medical devices are currently regulated as drugs or simply unregulated. Now, however, India’s health authorities plan to issue a set of guidelines to define and regulate medical devices as a separate category. These guidelines are being finalized in consultation with the device industry and the public, and should be issued soon by the health ministry.
The new guidelines primarily separate medical devices from drugs and call for stricter oversight from the Drug Controller General of India (DCGI) on both the manufacturing and import of medical devices. DCGI currently has a separate section to deal with medical device applications and monitoring, but it probably will need to expand after the publication of the medical device regulatory framework.
DCGI has also recently included 19 more medical devices under the Drugs and Cosmetics Act (DCA). Devices now requiring licenses for import, distribution and sale include: spinal needles, insulin syringes, endotracheal tubes, cochlear implants, annuloplasty rings, trachestomy tubes, heart lung packs, measure volume sets, hemodialysis tubing sets, blood tubing sets and dialysis catheters. DCGI plans a six-month transition for implementation based on an industry meeting in April 2009. Devices regulated under DCA since 2005 include heart valves, cardiac stents, orthopedic implants and internal prosthetic replacements.
Central Drugs Standard Control Organization
India’s Central Drugs Standard Control Organization (CDSCO) regulates the manufacture, sale and distribution of medical products. It is responsible for the approval and issuance of licenses for various medical products, such as vaccines, IV fluids and blood products, manufactured either in India or overseas.
CDSCO is currently organizing efforts to transition from a paper-based to an electronic document management system. There are up to 10,000 files on medical manufacturers, suppliers and importers in the current system. Registrations, evaluations, approvals, licenses and clinical trial approvals are all filed as physical documents. To improve the management of this vast amount of paperwork, CDSCO plans to scan these documents and archive them in electronic form.
CDSCO also plans to implement a document management system to build a completely computerized medical product control system. This full electronic system would cover the online processing of registrations, issuing and renewing licenses, disseminating policy documents and guidelines, and managing user feedback.
Clinical Trials
The clinical trial industry in India is also booming and projected to exceed $1 billion in 2010. The head of CDSCO, Surinder Singh, recently announced that the government will impose more-stringent regulations for clinical trials within the next few years. CDSCO recently created a team of industry and experts from nongovernmental organizations to develop a set of new guidelines, which should be in place by the end of 2009.
CDSCO will soon require mandatory registration of all contract research organizations (CROs) and ongoing clinical trials in India. The registry will be publicly accessible.
CDSCO plans to hire 94 new inspectors to monitor clinical trials and medical devices. A large proportion of the new inspectors will work on clinical trials only. CDSCO is currently training its officials with the help of the World Health Organization (WHO).
Indian officials are also planning surprise visits to clinical trial sites in the near future to ensure sites’ compliance with safety and quality regulations. Trials found to be violating these regulations will be suspended.
CONCLUSION
Asia ’s medical device regulatory requirements are ever evolving. China’s device regulatory system is focused on ensuring quality while India is still in the beginning stages of implementing a medical device regulatory framework. Both countries have some distance to go before their systems are fully functional. On the other hand, Japan is working towards increasing efficiency with their already developed regulatory system. With increased transparency in regulations, entering the Asian medical device market has become more accessible for medical companies.
Ames Gross is the president and founder of Pacific Bridge Medical. He is recognized nationally and internationally as a leader in Asian medical markets.
Momoko Hirose is a vice president at Pacific Bridge Medical. She works on consulting projects and research.