|Year : 2010 | Volume
| Issue : 3 | Page : 90-93
Registration of medical devices
General Manager, Regulatory Affairs Reliance Life Sciences Pvt. Ltd
|Date of Web Publication||20-Oct-2010|
General Manager, Regulatory Affairs Reliance Life Sciences Pvt. Ltd
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Globally the medical device (MD) market has been growing quite rapidly over the past decade. The regulatory framework for pharmaceuticals and devices differ substantially. The regulatory authorities in different regions of the world recognize different classes of medical devices (MDs), based on their design complexity, their use characteristics, and their potential for harm, if misused. With the vast majority of MDs in developing countries being imported, the respective governments need to put in place policies & regulations to address all elements related to MDs, ranging from its development, manufacturing, registration to post-marketing obligations & disposal so that public can have access to high quality, safe & affordable products for appropriate use. This article highlights current regulations pertaining to registration of MDs in India, in light of those existing in Global Harmonization Task Force (GHTF) member countries & Association of Southeast Asian Nations (ASEAN) countries.
Keywords: Medical device, Regulations, Registration.
|How to cite this article:|
George B. Registration of medical devices. Perspect Clin Res 2010;1:90-3
| Introduction|| |
Global statistics on MD manufacturers reveal that the US, Japan and EU countries manufacture approximately 85% of the MDs in the world. Implementing a full regulatory programme can be very demanding on resources, especially for a developing nation. A good approach to setting a clear direction for all stakeholders is to establish a comprehensive national policy or guideline on MD. The government can subsequently bring in legislation and enforcement to suit the country's conditions and needs. The GHTF, a voluntary group of international regulatory affairs experts from United States, the European Union, Canada, Australia and Japan for MDs is working towards harmonizing the regulation of MDs internationally. By following recommendations from the GHTF, countries can ensure that their regulatory controls are not in significant conflict with global harmonization recommendations. GHTF also provides a risk-based device classification system (Ref GHTF document SG1-N015R14).  The World Health Organization (WHO), with its partners, is also working towards achieving harmonization, which will have a significant impact on patient safety. The WHO guidelines emphasize the need for establishment license or registration which requires that the vendor either obtains a license or is registered before they are allowed to sell MDs. As per WHO guidance document, a "Vendor" is any person who sells medical devices. This person could be a manufacturer, an importer, a distributor, a wholesaler, or a retailer and a "Manufacturer" is any person who produces MDs. Advantages with registration is many folds. It ensures that the government can i) have a record/listing of the vendor; ii) lay emphasis on after-sale obligations; iii) enforce orders on defaulters like suspension of licenses iv) have a renewal system in place for registration thereby maintaining updated information. 
| Regulations pertaining to registration of MDs in GHTF member countries|| |
In the United States, MDs are regulated by the FDA Center for Devices and Radiological Health (CDRH). The establishment (manufacturers, initial importer, specifications developer, contract sterilizer, re-packager and/or re-labeler) must be registered with the FDA as per FDA 2891- 21 CFR Part 807. The FDA regulatory classification system is based on MD intended use & level of risk rather than on technologies and procedures. The MD Amendments was passed in 1976. This law introduced a series of general controls for MDs including registration and listing, requirements for production using good manufacturing practices, and requirements for post-market reporting of device failures. Class I includes devices that is subject to only the general controls such as registration and listing, record keeping, good manufacturing practices, and other general provisions of the act. Most of these are exempt from premarket review. Class II includes those that are subject to special controls such as performance standards, postmarket surveillance, patient regulations, or guidance documents. Most class II and some class I devices require pre-market entry notification (termed 510k, an information package for the FDA, which is subject to less stringent review than the premarket approval (PMA) process. The 510k submission must demonstrate how the proposed MD is substantially equivalent to a MD that is already on the US market (a predicate). The FDA receives more than 3,000 510(k) submissions every year. Class III devices, represent the highest level of risk & require PMA through the submission of clinical and nonclinical data (e.g., design and manufacturing data) to demonstrate safety and effectiveness, but not necessarily efficacy. Devices that are not found by the FDA to be substantially equivalent to a predicate require PMA letter from FDA. 
In the European Union (EU), there are 3 harmonized directives that apply viz:
- Medical Devices Directive 93/42/EEC
- Active Implantable Medical Devices Directive 90/385/ EEC
- In Vitro Diagnostic Directive 98/79/EC
The manufacturers have to meet the requirements of the EU directive to get the Communaute Europeenne (CE) marking on a MD. This marking is mandatory for marketing and the free circulation of the MDs in the EU countries. This directive also applies to contract manufacturers. To carry out the certification of conformity procedures, the manufacturer may apply to the notified body (a public or private organization that has been accredited to validate the compliance of the device to the European Directive) of his choice in any EU country. The manufacturers of devices of classes II and III, as well as devices of class I with either measuring function or sterility requirements, must submit to the regulator (competent authority): (1) a Declaration of Conformity to the appropriate EC Directives, and (2) details of the conformity assessment procedure followed. In addition, for higher risk class devices that require design examination or type examination, the corresponding EC-Certificates issued by a notified body must also be submitted to the competent authority. Other MDs of class I are exempt from pre-market submissions, although they must follow the essential principles of safety and performance in their design, construction and labeling requirements.  From 21st March 2010, a new EC Directive 2007/47/EC has become effective, impacting Directives 90/385/EEC and 93/42/EEC. MDs according to 90/385/EEC or 93/42/EEC would also need to comply with this new Directive; otherwise the products cannot be placed on the European market.
In Canada, a Device Licence is awarded by the Therapeutic Products Directorate. Any individual or company wishing to sell MDs for human use must apply for permission to obtain an MD establishment licence (MDEL), with certain exceptions. The device classification is again risk based and generally corresponds to the European Council Directive 93/ 42/EEC (MDD) devices. Class I devices are exempted from pre-market submission, but they must still satisfy the safety, effectiveness and labeling requirements. Devices of classes III and IV are subject to in-depth regulatory scrutiny, while class II devices require only the manufacturer's declaration of device safety and effectiveness before sale. One MDEL can apply to one or many sites provided the activities conducted at these sites are operated by the same legal entity. 
The Therapeutic Goods Administration (TGA) is the government body that regulates MDs in Australia. Registration is based upon the recommendations of the GHTF. The new MDs legislation was passed by the Australian Parliament in April 2002. All "registrable" devices must undergo rigorous pre-market evaluation before market entry. "Listable" devices are less rigorously regulated, but may be evaluated for safety (not efficacy) if there are regulatory concerns about the risk profile of the product. The sponsor or his designated agent can register online the MD on the Australian Register of Therapeutic Goods (ARTG) after receiving information from the manufacturer on class of the device, its intended purpose; Global Medical Device Nomenclature (GMDN) code and term; conformity assessment certification & Australian declaration of conformity.  The sponsor must also hold an Enterprise Identification Number before being permitted to apply to register or list products. Under some circumstances, the manufacturing facilities may need to be licensed as well.
In Japan, The Ministry of Health, Labor and Welfare is working on the Pharmaceutical Administration Law (PAL, enforced as of April 2005) revision towards risk-based MD regulation, in line with the GHTF principles. To market MDs in Japan, the Marketing Authorization Holders (MAH), must register the device, regardless of its classification. To register and market "General MDs" (Class I devices), the MAH only need to file Pre-Market Submission to Pharmaceutical & Medical Devices Agency (PMDA) with no assessment by the PMDA. For "Specified Controlled MDs" which falls under Class II devices, the MAH needs to file Pre-Market Approval application with a Registered Certification Body (RCB) and obtain their certification. This procedure is quite similar to European CE Marking using a Notified Body. To register and market a "Highly Controlled MD" (Class III & IV devices), the MAH needs to file a Pre-market Approval Application with the PMDA and obtain their approval. MD sales organizations must have a licence called "Hanbai-Gyoo" or "Hanbai Todoke". Foreign manufacturers must go through the process of accreditation.  In addition, importers are required to have a licence called "Yunyu Hanbai-Gyo".
| Status in ASEAN nations|| |
ASEAN, an economic grouping of 10 countries in Southeast Asia has set up a committee responsible for MD regulatory harmonization - The Medical Device Product Working Group (MDPWG). The MDPWG is in the process of finalization a unified set of rules for MDs, which would be called "ASEAN Medical Device Directive (AMDD)" Currently, out of the 10 ASEAN countries, 6 have laws or "administrative guidelines" that govern MDs. Though AMDD will not be a law in ASEAN countries, but all member countries will be required to pass laws with the same provisions. Product registration will be the major focus area of the AMDD.  In Singapore, (a key country within ASEAN), before a device dossier or product registration application is submitted, the Health Sciences Authority (HSA) initially verifies that the product qualifies as a MD under the Health Products Act. Only upon confirmation, the application process actually begins. Registered MDs are listed on the Singapore Medical Device Register (SMDR). Dossier for product registration is based on ASEAN common submission dossier template (CSDT) format. From 1st of May 2010, supply of unregistered Class B, C and D devices will be prohibited.
| Scenario in India|| |
India's MD market is currently the fourth largest market in Asia. MDs and supplies market is expected touch USD 1.7 billion in 2010 as per a sector report from National Institute of Pharmaceutical Education and Research (NIPER). Imports constitute over 50% of the market. The MDs market for exports is estimated around USD 509 million.
Based on Mashelkar Committee recommendation in 2004, steps were initiated towards creation of a specific MDs division within the Central Drugs Standard Control Organization (CDSCO). After the approval from the Drugs and Consultative Committee (DCC) in July 2005, in gazette notifications issued in October 2005, the Ministry of Health and Family Welfare (MOHFW) declared 10 sterile devices; to be considered as drugs and consequently regulated for their import, sale and manufacture under Section 3(b) (iv) of the D&C Act.  It was also notified that, the control over manufacture of these 10 devices would be exercised by CLAA i.e. DCG (I) under the said Rules. These MD guidelines finally came into effect from 29 th June 2006. Based on large number of requests seeking clarity from both manufacturers of MDs and their representatives from India and abroad, CDSCO have time and again posted on their website clarifications & explanations on the guidelines. On 20 th March 2009 vide the clarification issued by CDSCO; an additional 19 sterile MDs have been covered under the provisions of D&C Act and Rules. Further, if the end use of the notified device is a sterile product, it will fall within the ambit of the notification (e.g. certain orthopedic implants which are imported as non-sterile devices and sterilized in the hospitals before use) and would have to go through the registration and import licence process.
Application for Registration Certificate (issued in Form 41) in respect of the premises and the devices manufactured and meant for import into India is required to be made by the manufacturer or importer or his agent in India, in Form 40 as under Rule 24A of the Drugs and Cosmetics Rules. However, the information and undertakings required to be furnished under Schedule DI and DII can be modified to suit the requirements of devices (as given in the guidance doc effective from June 2006) in place of normal pharmaceutical products. The fee structure is also same as like for drugs except for the fact that registration of a single MD can include variation in sizes or shape without any change in the material or method of use. A fee of US$ 1000 or its equivalent shall be paid for registration of each additional device. The import licence is issued on Form 10. Free Sale Certificate in country of origin issued by the Ministry of Health/National Regulatory Authority is a pre-requisite for the registration.
For manufacturing of the notified sterile devices in India, application has to be made in Form 27 to the state licencing authority with relevant details on the product and manufacturing site. The CDSCO website provides listing of all the manufacturers who have been granted approval/licence on Form 28 by CLAA for manufacturing of notified MDs till 31 st Dec 2009. The formats for issuance of Market standing certificate, non conviction certificate and performance certificate for MDs are also displayed. In case of devices belonging to the notified category, which has not been manufactured in the country before the date of notification, no manufacture would be permitted without the approval of the competent authority as per norms prescribed. Any change in the Design and/or change in material and/or change in composition of an already approved/registered MD will require prior approval of DCG (I).
With a view to raise the level of control on MDs, the Government has also revised the Schedule MIII of Drugs & Cosmetics Rules 1945 and posted it on CDSCO website for public opinion.  As per the revised draft, the 'manufacturer' means "the natural or legal person with responsibility for the design, manufacture, packaging and labeling of a device before it is placed on the market under his own name,( regardless of whether these operations are carried out by that person himself or on his behalf by a third party). The obligations of this Directive to be met by manufacturers also apply to the natural or legal person who assembles, packages, processes, fully refurbishes and/or labels one or more readymade products and/or assigns to them their intended purpose as a device with a view to their being placed on the market under his own name". The MDs have been classified into Class A, B, C & D as per their level and intended use (Refer [Table 1]). All MDs sold in this country (except for custom made devices, meant for a particular patient use) should, as a general rule, bear the ICAC mark (Indian Conformity Assessment Certificate) to indicate their conformity with the provisions of this schedule. 
The "accessories" intended specifically by manufacturers to be used together with a 'parent' MD to enable that MD to achieve its intended purpose are subject to the same procedures as apply to the MD itself. For sterile devices, manufacturers would be expected to comply with the specific requirements for sterile product facility laid down in Schedule M-I, Part I-A. Appropriate and adequate testing laboratories for assessment of MDs like CDTL, Mumbai would have to be set up.
While the authority regulating MDs continues to be the CDSCO, in the Ministry of Health, The Department of Science & Technology (DST) has come out with a Draft "MD Regulation bill" which has been hosted for inviting comments, suggestions etc.  The Government of India is also proposing to set-up the Indian Medical Devices Regulatory Authority (IMDRA). The IMDRA is expected to formulate appropriate guidelines to be a national certifying and regulatory agency in India for medical equipment and devices.
| Conclusion|| |
It is imperative for regulatory agencies to work towards achieving harmonized regulatory systems to raise the quality of MDs in their respective country to meet international standards. Policies and regulations should be reviewed periodically to respond to changes in technologies by incorporating appropriate amendments. Indian government has taken several initiatives towards this harmonization by bringing out new guidelines, drafting MD Regulation bill, revamping the Schedule M-III, publication and dissemination of guidance documents and public awareness through several meetings and hosting clarifications on CDSCO site. The industry has also geared up as reflected from the increased number of MD applications received/processed by the CDSCO having incrementally gone up from 0 (in 2005) - 300 (in 2006) - 450 (in 2007) - 400 (in 2008) and 936 (in 2009).
| Acknowledgments|| |
I gratefully acknowledge the encouragement and support of Reliance Life Sciences Pvt. Ltd in carrying out this work ( www.rellife.com ).
| References|| |
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