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Medical device regulation for manufacturers P McAllister* and J Jeswiet Department of Mechanical Engineering, Queen’s University, Kingston, Canada Abstract: Manufacturers of medical devices are held to a higher standard than manufacturers of many other products due to the potential severity of the consequences of introducing inferior or unsafe products to the market-place. In Canada, the medical device industry is regulated by Health Canada under the Medical Device Regulations of the Food and Drug Act. The Medical Device Regulations dene requirements of medical device design, development and manufacture to ensure that products reaching the public are safe and eective. Health Canada also requires that medical device manufacturers maintain distribution records to ensure that devices can be traced to the source and consumers can be contacted successfully in the event that a device is recalled. Medical devices exported from Canada must be compliant with the regulations of the country of import. The Canadian Medical Device Regulations were based on the Medical Device Directives of the European Union thus facilitating approval of Canadian devices for the European market. The United States Food and Drug Administration has separate and distinct requirements for safety and quality of medical devices. While eort has been made to facilitate approval and trade of Canadian medical devices in the United States and the European Union, obtaining approval from multiple regulatory bodies can result in increased device development time and cost. The Global Harmonization Task Force is an organization composed of members from Japanese, Australian, European, Canadian and American medical device regulatory bodies. This organization was formed with the objective of harmonizing medical device regulations in an eort to facilitate international trade and standardize the quality of medical devices available to all countries. This paper discusses the requirements that must be met by manufacturers when designing and manufacturing medical devices. Keywords: medical device manufacture, medical device regulation, ISO 13485, ISO 13488, Health Canada IVDD MDD
NOTATION ASTM CE CEN CSA DIN FDA, US FDA GMP
ISO
American Society for Testing and Materials Conformite´ Europe´en European Committee for Standardization Canadian Standards Association Drug identication number United States Food and Drug Administration Good Manufacturing Practices ( US FDA’s manufacturing standards) International Standards Organization
MDR PMA PNC
SPN 510k
1 The MS was received on 10 June 2002 and was accepted after revision for publication on 16 June 2003. * Corresponding author: Department of Mechanical Engineering, Queen’s University, Kingston, Ontario, Canada K7L 3N6. email:
[email protected] H05502 © IMechE 2003
in vitro diagnostic device Medical Device Directive ( European Union) Medical Device Regulation (Health Canada) Pre-market approval Preferred name code (associated with Canada’s Medical Device Regulations) Standard product nomenclature ( US FDA) US FDA abbreviated pre-market approval process for devices that are substantially equivalent to a predicate device
INTRODUCTION
Medical devices have been identied as unique products requiring strict regulation. The special nature of medical devices is due to their potential to cause harm to users Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
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and operators in the event of device failure. Products considered to be medical devices include those intended to treat, mitigate or diagnose disease or return normal function to the body or a body part. The denition of a medical device extends to all of the device’s components or constituent parts and controlling software, but excludes drugs. The production and sale of drugs is controlled by a separate set of regulations. The denition of a medical device varies from country to country. In Canada, the regulation of medical devices is limited to devices intended for use in the treatment of humans; however, the United States’ denition of medical devices includes veterinary devices. Dierences in medical device regulation between countries require that manufacturers comply with several sets of regulations. Thus familiarity with the medical device regulations of each country in which the device will be sold is essential. Although this paper deals with regulation of medical devices in Canada and North America, the rules and regulations applicable to Canada can also be seen to apply in many other jurisdictions. The discussion of medical device regulation in Canada will provide the manufacturer with a map to the set of guidelines that must be followed in getting a new device to market.
manufacturer that the medical device is safe for use and eective for its intended purpose. Health Canada classies medical devices based on the level of risk to patient and user. The level of risk associated with the device is dependent on the intended purpose of the device, the type of contact with the patient, the technology internal to the device and the severity of the consequences of failure of the device. Medical devices are grouped in four risk classes with Class I containing low-risk devices and Class IV containing high-risk devices. The amount of regulation associated with a class of devices is commensurate with the assessed level of risk of the devices within the class. When applying for a new medical device licence, it is critical that the manufacturer correctly identies the classication of the device since each device class has a dierent associated set of compulsory elements to complete the application. If Health Canada determines that the device has been incorrectly classied, the licence application may be found to be incomplete. The manufacturer will be required to resubmit the licence application with the addition of the missing elements. The submission of incomplete licence applications results in delays to the application process and hence delays in getting the product to market.
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2.2 New medical device licensing
CANADIAN MDR: A BRIEF HISTORY
The Medical Device Regulations (MDRs) were enacted in 1998 as part of the Canadian Food and Drug Act, replacing preceding regulation from 1976. The MDRs of 1998 were harmonized with the Medical Device Directives of the European Union enacted in 1993. Prior to 1993, each of the European Union’s member states had its own medical device regulatory body and consequently its own unique set of requirements for medical devices marketed within the borders of the member state. It was recognized that medical device regulation diered between member states creating an impediment to free trade across borders. The Medical Device Directives represent a harmonization of the medical device regulations of the multiple members of the European Community. In an eort to greater facilitate trade with the European Community, Canada’s MDRs bear substantial similarity to the Medical Device Directives of the European Community. As of 1 July 1998, all new medical devices oered for sale in Canada are required to comply with the MDRs. All medical devices marketed in Canada require a Medical Device Licence that is issued by Health Canada to the manufacturer of a medical device once compliance with the MDRs has been established. 2.1 Pre-market requirements The issuance of Medical Device Licences by Health Canada depends on successful demonstration by the Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
A new medical device licence must be obtained by a manufacturer prior to marketing a medical device in Canada. A medical device is dened under the Food and Drug Act as: ‘Any article, instrument, apparatus or contrivance, including any component, part or accessory thereof, manufactured, sold or represented for use in: 1. The diagnosis, treatment, mitigation or prevention of disease, disorder or abnormal physical state, or its symptoms, in human beings. 2. Restoring, correcting or modifying a body function or the body structure of human beings. 3. The diagnosis of pregnancy in human beings. 4. The care of human beings during pregnancy and at and after birth of the ospring, including care of the ospring. And includes a contraceptive device but does not include a drug.’
Once it has been determined that the product is a medical device and requires a licence, the manufacturer can proceed to classify the device using the appropriate classication scheme. As well as distinguishing between drugs and medical devices, Health Canada also makes a distinction between medical devices and in vitro diagnostic devices ( IVDDs). There are separate requirements for licence applications for IVDDs. This paper will only deal with requirements specic to medical devices. 2.2.1 Device classication The rst and arguably the most important step in completing an application for a new medical device licence H05502 © IMechE 2003
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is determining the device classication. As mentioned above, there are four risk-based classes into which medical devices are grouped. Each class has an associated list of required elements to complete the medical device licence application. The classes do have some elements in common, however. Health Canada denes the four risk classes as [1]: 1. Class I contains low-risk devices. These are devices that provide virtually no risk to the patient or the operator of the device either by the functions they perform or the materials from which they are made. An example of a Class I medical device is a wooden tongue depressor. 2. Class II contains medium-risk medical devices such as surgically invasive devices that remain in continual contact with the body for less than 30 days, and do not interact with the central cardiovascular system, the central nervous system, or a foetus in utero. This class also contains non-invasive devices that are intended to come into contact with injured skin and invasive devices that contact the surface of the eye or pass through a natural body orice. Examples of Class II devices include needles and scalpels. 3. Class III contains high-risk medical devices such as invasive medical devices that remain in contact with the body for at least 30 days, but do not directly contact the central cardiovascular system, the central nervous system or a foetus in utero. An example of a Class III device is a total hip replacement. 4. Class IV contains high-risk medical devices, the failure of which would result in serious deterioration of health or death of the patient or operator. An example of a Class IV device is an articial heart valve. Medical device classication relies on a set of 16 rules. These are grouped into four sections pertaining to particular types of devices: 1. 2. 3. 4.
Invasive devices: apply rules 1 to 3. Non-invasive devices: apply rules 4 to 7. Active devices: apply rules 8 to 12. Special rules: apply rules 13 to 16.
Health Canada denes an invasive device as ‘a medical device that is intended to come into contact with the surface of the eye or penetrate the body, either through a body orice or through the body surface’. Rules 1 to 3 group invasive devices in Classes I to IV depending on the duration of contact with the body and the system aected. Rules 4 to 7 apply to non-invasive medical devices. Non-invasive devices again fall into Classes I to IV depending on the type of contact with the body and the function performed. Rules 8 to 12 pertain to active devices. Health Canada denes an active device as: ‘a medical device that depends for its operation on a source H05502 © IMechE 2003
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of energy other than energy generated by the human body or gravity. A medical device that transmits or withdraws energy or a substance to or from a patient without substantially altering the energy or substance is not an active device.’
Rules 8 to 12 classify active devices into Classes I to IV depending on the purpose of the device, the technology used and the level of risk posed to the patient by the technology. The ‘special rules’, rules 13 to 16, pertain to specic tasks and devices. Rule 13 deals with devices intended to sterilize or disinfect. Devices intended to disinfect blood, tissues and organs fall into Class IV; devices intended to sterilize medical devices fall into Class II. Rule 14 addresses devices incorporating non-viable animal or human tissue and derivatives achieved through recombinant DNA technology. All such devices are grouped in Class IV unless they only come into contact with the skin, in which case they are classied in Class I. Rule 15 addresses materials sold to be shaped and incorporated into medical devices. Such materials are given the same classication as the device for which they are intended. Rule 16 applies specically to breast implants and tissue expanders for breast reconstruction and augmentation. Under rules 1 to 7 for invasive devices, breast implants could be classied in Class III based on rule 1, subrule 3, however breast implants are considered higher risk since failure of the implant can have widespread systemic eects. Rule 16 places these devices in the highest risk category, Class IV. 2.2.2 Application requirements Application requirements dier for each class of medical device. Class I devices are exempt from licensing. This means that a manufacturer does not have to obtain approval from Health Canada in order to market the device. However, manufacturers of Class I devices are responsible for maintaining records of sales and distribution of their devices to ensure that the device can be traced should adverse events occur or in the event of emerging information that would reclassify the device in a higher risk category. All other medical devices are required to submit completed licence applications and obtain approval from Health Canada prior to being marketed in Canada [2, 3]. The application for device licensing of Classes II, III and IV devices includes some common elements in addition to special requirements specic to each device class. The common elements include: 1. Device classication that involves checking the appropriate box. 2. Device name as it appears on the product label. 3. Application history including whether the device has been granted licence under the Investigational Testing or Special Access provisions of the regulations. Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
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4. Name and address of manufacturer as it appears on the label. 5. Mailing address for regulatory correspondence. This information could dier from the manufacturer’s in the event that a device importer or manufacturer’s representative is completing the licence application. The licence, however, is always granted to the manufacturer as indicated in item 4 regardless of the applicant. 6. Licence application type: the applicant is requested to identify whether the licence will cover a single device or multiple medical devices (e.g. a range of sizes or a surgical kit). 7. Device preferred name code ( PNC ), optional. The PNC is a ve-digit identier assigned to each generic medical device type by the Medical Device Bureau. The PNC has been harmonized with the US FDA’s standard product nomenclature (SPN ) code. The PNC can be looked up in the Keyword Index from Health Canada. If an appropriate PNC cannot be located, this should be indicated on the application. 8. The applicant is asked to indicate whether the device is a near-patient IVDD or an IVDD sold for home use. 9. The applicant is asked to identify and indicate the medical specialty most closely associated with the intended use of the device. 10. If the device contains a drug, the applicant is required to identify the drug by its drug identication number (DIN ) and provide the brand or trade name and the active ingredient. If the drug does not have a DIN, then the applicant must assert that the drug meets requirements for safety, ecacy and quality, as required. 11. The purpose of the device must be described in sucient detail to conrm the correct classication of the device. 12. Additional details about the device must be provided including device names, previously assigned device identication numbers, and associated model and catalogue numbers. (a) Specic requirements for Class II device licences Licence applications for Class II devices require that the applicant assert the safety and ecacy of the device. Class II device licence applicants must provide assertion that the safety and ecacy have been tested and that the data exist to support this conclusion. Class II device licence applicants are not required to submit this data, however. They are only required to grant Health Canada access to this data should Health Canada request it. The specic requirements for Class II device licences include: 1. A list of all standards complied with in the manufacture of the device. A list of recognized standards has been provided by Health Canada. Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
2. The applicant must provide an attestation of safety and eectiveness of the device. The manufacturer must have objective evidence of the safety and eectiveness of the device. This evidence must be available to Health Canada on request. 3. The applicant must provide attestation that the labelling of the device is compliant with the Medical Device Regulations. 4. The applicant must provide attestation when the device is an IVDD that it has been tested on human subjects similar to the intended user and under conditions similar to those expected during regular use. 5. If a drug not having a DIN is included in the device, the applicant must provide attestation that the drug is safe, eective and meets quality requirements. 6. As of July 2003, manufacturers of Class II medical devices will be required to prove compliance with standard ISO 13488-98: Quality Systems—Medical Devices: Particular requirements for the application of ISO 9002, as amended from time to time. The applicant must provide attestation of compliance with ISO 13488-98. 7. The manufacturer must sign the application. (b) Application requirements for Class III and Class IV devices Class III and Class IV device licence applications require more accompanying documentation than Class II devices. Class III devices must provide documentation giving evidence of safety and eectiveness of the device. This evidence must include: 1. A description of the device and of the materials used in its manufacture and packaging. 2. A description of the features of the device that permit it to be used for the medical conditions, purposes and uses for which it is manufactured, sold or represented. 3. A list of the countries other than Canada where the device has been sold, the total number of units sold in those countries, and a summary of any reported problems with the device and any recalls of the device in those countries. 4. A list of the standards complied with in the design and manufacture of the device to satisfy the safety and eectiveness requirements. 5. In the case of a device to be sold in a sterile condition, a description of the sterilization method used. 6. A summary of all studies on which the manufacturer relies to ensure that the device meets the safety and eectiveness requirements, and the conclusions drawn from those studies by the manufacturer. 7. A copy of the device label. 8. In the case of a near-patient in vitro diagnostic device, a summary of investigational testing conducted on the device using human subjects representative of the intended users and under conditions similar to the conditions of use. H05502 © IMechE 2003
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9. A bibliography of all published reports dealing with the use, safety and eectiveness of the device. 10. As of 1 July 2003, an attestation by a senior ocial of the manufacturer, based on an audit by an organization that performs quality system audits, that the quality system under which the device is designed and manufactured satises National Standard of Canada CAN/CSA ISO 13485-98, Quality systems—Medical devices—Particular requirements for the application of ISO 9001, as amended from time to time. Class III device applications for devices containing drugs not having a DIN must include attestation of the safety, ecacy and quality of the drug. The manufacturer’s signature is also required on the Class III device application. Class IV devices have similar requirements with some additions, including: 1. A risk assessment comprising an analysis and evaluation of the risks, and the risk reduction measures adopted to satisfy the safety and eectiveness requirements. 2. A quality plan setting out the specic quality practices, resources and sequence of activities relevant to the device. 3. The specications of the materials used in the manufacture and packaging of the device. 4. Details of the manufacturing process of the device. 5. Detailed information on all studies on which the manufacturer relies to ensure that the device meets the safety and eectiveness requirements, including: (a) pre-clinical and clinical studies; (b) process validation studies; (c ) if appropriate, software validation studies; (d ) literature studies. 6. In the case of a medical device other than an in vitro diagnostic device, manufactured from or incorporating animal or human tissue or their derivative, objective evidence of the biological safety of the device. 7. In the case of a near-patient IVDD, detailed information on investigational testing conducted on the device using human subjects representative of the intended users and under conditions similar to the conditions of use. 8. A summary of the pre-clinical and clinical studies and the conclusions drawn from those studies by the manufacturer. 9. A summary of the investigational testing for an IVDD and the conclusions drawn from that testing by the manufacturer. All other requirements for Class IV device licence applications are the same as those for Class III devices. In some cases, the only dierence in the applications is H05502 © IMechE 2003
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that details are required for Class IV devices where a summary suced for Class III devices. 2.2.3 Safety standards There are a number of standards recognized by Health Canada [4]. Manufacturers are required to comply with all recognized standards applicable to their product. Compliance of the device is evaluated by an authorized third-party test facility. The standards recognized by Health Canada relate to: (a) materials strength and composition for specic applications; (b) mechanical test methods for devices; (c) biocompatibility of materials and devices; (d ) sterilization processes; (e) impact of degradation and leachate products; (f ) safety issues for electrical devices; (g) safety issues associated with blood treatment devices. Health Canada draws standards from internationally recognized bodies such as the International Standards Organization ( ISO), the American Society for Testing and Materials (ASTM ), the Canadian Standards Organization (CSA) and the European Committee for Standardization (CEN ). In some cases, the standards may be altered from their original text or Health Canada may recognize only parts of standards. Standards may be revised from time to time by the publishing body. When this occurs, Health Canada will review the document and may or may not approve the new version. Licence applications for new medical devices must be compliant with the standards recognized by Health Canada and not simply the latest version of the standard. 2.2.4 Quality system standards As mentioned in the application requirements, as of 1 July 2003 all manufacturers of Classes II to IV medical devices will be required to prove compliance with CAN/CSA ISO 13488 and 13485 standards [5]. These standards provide requirements for the successful implementation of a continually improving quality management system for designing and manufacturing medical devices. At the time this paper was written, standards CAN/CSA ISO 13488 and 13485 were not stand-alone normatives. These standards supplement ISO 9002 and 9001 respectively. The ISO 9000 series standards provide a framework for the documentation, implementation, maintenance and improvement of a quality management system for any industry. Special requirements of quality systems for the medical device industry are given in ISO 13485 and 13488. The primary function of the ISO 9000 series standards is to ensure that procedure for design, manufacture, installation and maintenance of products is implemented Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
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and suciently well documented to ensure that all employees understand the impact of their actions on the overall perceived quality of the product and that the quality of the product is consistent and meets customer, as well as regulatory or statutory, requirements. The ISO 9001/9002 standards can be summarized as a closed-loop ‘plan–do–check–act (PDCA)’ system. The ‘plan’ phase is accomplished in cooperation with the customer. The customer and the manufacturer establish the goals, requirements and processes that will achieve the desired product. The ‘do’ phase refers to the implementation of the processes. In the ‘check’ phase, completed products and processes are measured, analysed and compared against the objectives and requirements established in the ‘plan’ phase. Dierences between the output and the desired output are addressed in the ‘act’ phase. The ‘act’ phase of the system is the phase that ensures continual improvement of the quality management system. During the ‘act’ phase, decisions are made and actions are taken to aid the achievement of the objectives and requirements of the product based on the results from the ‘check’ phase. The ISO standards establish a chain of responsibility for the allocation of resources to the quality management system, product realization, quality system measurement, analysis and feedback, quality system evolution and the interaction between the organization and the customer. ISO 13485 species additional requirements for medical device manufacturers including: (a) provision of training for employees who must work under special environmental conditions or are required to use unfamiliar tools; (b) risk assessments are required whenever design changes are proposed after the design has been frozen; (c ) records of purchase of components and materials from external sources must be maintained; (d ) customized devices must be identied and kept separate from other devices; (e) sterilization processes and settings must be monitored, controlled and documented; (f ) environmental factors of packaging and storage that could be detrimental to the performance of the device must be documented. Certication of the quality management system is granted by authorized agencies. These agencies audit the documentation and implementation of the quality management system.
and that medical devices do not present unwarranted risks to the population of Canada. Health Canada achieves post-market surveillance by requiring that the manufacturer report adverse events when they become aware of adverse events, or the institutions in which adverse events have occurred. Adverse events are occasions on which a device has caused or may have contributed to the serious deterioration of health or the death of a patient or operator. Manufacturers or importers of the device are required to le both preliminary and nal adverse event reports indicating what action has been taken to correct and prevent future adverse events. If the action taken by the manufacturer is not to the satisfaction of Health Canada, or if Health Canada is concerned about the risk posed by the device to the public, Health Canada has the authority to recall the device and prevent future sales until satised by the corrective action of the manufacturer. Accountability for the performance of the device lies with the manufacturer. Traceability provided by distribution records and export certicates facilitates successful contact of those people aected by unsafe devices during a medical device recall.
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EXPORTING DEVICES
Canadian manufacturers of medical devices often export their products in order to reach a greater market base. The only requirement that Health Canada imposes on exported medical devices is that the manufacturer completes export certicates for each shipment. Export certicates are maintained to facilitate traceability with exported products. In the export certicate, the exporter is asked to indicate what products are contained in the shipment and the destination of the shipment. The export certicate also declares that the product is compliant with the medical device regulations of the country of destination. The United States and the European Community are common destinations for Canadian device manufacturers. For this reason, it is important the Canadian device manufacturers are familiar with the US FDA’s Safe Medical Device Regulations and the European Community’s Medical Device Directives.
3.1 Exporting to the United States The US FDA regulates the sale of medical devices in the United States. All devices marketed in the United States must have approval by the FDA prior to sale in the United States.
2.3 Post-market surveillance Post-market surveillance by Health Canada is intended to ensure that devices approved by Health Canada continue to perform as expected from the time of application Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
3.1.1 A brief history of the US FDA Prior to 1976, medical devices were regulated under the Food, Drug and Cosmetics Act of 1938. In the 1950s H05502 © IMechE 2003
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and 1960s attention was drawn to the dangers posed by unregulated medical devices. It was found that the Food, Drug and Cosmetics Act was inadequate when it came to regulating devices. It was estimated that over a 10-year period, 10 000 injuries were associated with medical devices of which 731 resulted in death [6, 7]. It was determined by the Cooper Committee that regulations were required that were specic to medical devices. In 1976, the Medical Device Amendments were passed. Any medical devices introduced to the market after 1976 were subjected to the full regulation of the Medical Device Amendments under the FDA. The Medical Device Amendments were intended to ensure that any medical device marketed in the United States is safe, eective and properly labelled for use. 3.1.2 Device classication The FDA categorizes medical devices in three risk-based classes. Class I contains low-risk devices, Class II medium-risk devices and Class III contains high-risk devices. The classication corresponds with Health Canada’s classication scheme with Canada’s Classes III and IV devices corresponding closely to the FDA’s Class III devices with some exceptions. The most notable dierence between the FDA’s classication scheme and Health Canada’s classication scheme is that all novel technology falls into the highest risk class, Class III, under the US FDA’s classication scheme. The FDA recognizes that there is an unquantiable amount of risk presented by relatively unproven technology. Once a device has been approved by the FDA and has been marketed as a Class III device because of its use of new technology, it is possible to have the device reclassied based on its performance and reputation over an extended period of time. 3.1.3 Pre-market notication The US FDA requires that all medical device manufacturers provide notication of the intention to sell their product at least 90 days prior to marketing the device. Pre-market notication may be achieved by one of two avenues: pre-market approval (PMA) or the 510k process [8, 9]. The PMA is a long, detailed process similar to the application process for Health Canada’s new medical device licence. A PMA is required for all Class III medical devices with the exception of those medical devices similar to Class III devices that were legally marketed in the United States prior to 1976 and for which a PMA has not been requested since. The 510k process is an abbreviated approval process. The 510k is available to manufacturers of Class I and Class II devices that can be proven ‘substantially equivalent’ to a predicate device. A predicate device is a device that is already legally marketed in the United States under the approval of the FDA. Substantial equivalence H05502 © IMechE 2003
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indicates that a device has the same intended purpose as a predicate device, uses the same technology as a predicate device and poses no new risks to patients. Once a verdict of substantial equivalence is determined, the 510k application process may take as few as 90 days to complete. 3.1.4 Good Manufacturing Practices Good Manufacturing Practices (GMPs) were implemented in 1978. The GMPs were intended as a quality assessment and control mechanism. GMPs are similar in this respect to ISO 13485; however, they are much more specic and considered to be a more stringent standard. Manufacturers of Class I devices are exempt from GMPs. Manufacturers of Class II and III devices are required to prove compliance with GMPs prior to marketing devices in the United States. 3.1.5 Post-market surveillance Post-market surveillance mechanisms are similar to those in Canada and the European Community. 3.2 Exporting to the European Community Exporting medical devices to Europe from Canada is simplied by the amount of harmonization between the Medical Device Regulations and the Medical Device Directives [5]. 3.2.1 A brief history of the Medical Device Directives Prior to 1992, each member state of the European Union had its own medical device regulatory body with its own unique set of requirements for the sale of medical devices. With the formation of the European Union, the separate regulating bodies were viewed as an impediment to trade and consistency of the state of the art in medical technology. In 1992, the Medical Device Directives were implemented. These directives harmonized medical device regulations and were adopted by most member states of the European Union. All devices marketed in the European Union must obtain certication by an authorized body. Proof of certication is exhibited by the Conformite´ Europe´en (CE ) mark. The CE mark can only be axed to those devices that pass an audit by a certied body and comply with the safety, eectiveness and quality requirements specied in the Medical Device Directives. Only manufacturers of Class I devices that neither are sterilized nor provide a measuring function, and custom-made devices on systems are exempt from audit by certied body. 3.2.2 Device classication The Medical Device Directives also use a rule-based classication scheme to categorize medical devices into Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
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one of four risk-based classes. Class I devices are lowrisk devices, Class IIa contains medium-risk devices and Classes IIb and III contain high-risk devices. The device classication is very similar to Health Canada’s classication scheme. 3.2.3 Device assessment There are several assessment routes available to each device class depending on the specic nature and characteristics of the device. All devices must comply with the essential requirements associated with the device class, as well as the special requirements associated with the device type. Device assessment is performed by an authorized third party. The authorized party audits the manufacturer’s site, process documentation and quality management system and performs type-testing on the product to ensure safety and eectiveness of the device by testing to ASTM, CEN and other internationally recognized standards. Once a successful audit has been performed, the manufacturer can ax the CE mark and sell its product on the European market. 3.2.4 Quality management system The European Community requires that manufacturers of medical devices implement a quality management system. While the regulations do not specify a standard to which the quality management system must adhere, the ISO 13488 and ISO 13485 documents were prepared in conjunction with the European Community. Therefore, a quality system must at least meet the ISO standards to be granted certication. It is recommended that manufacturers wishing to market their devices in the United States implement the quality management system dened in the Good Manufacturing Practices since the GMPs are considered to provide a higher standard than ISO. Health Canada has instituted a system of Mutual Recognition Agreements that would allow Canadian manufacturers to have their quality management systems certied for both ISO certication and the CE mark simultaneously, thus avoiding the cost of multiple audits. 3.2.5 Post-market surveillance Health Canada’s post-market surveillance system is based on the European model and therefore the two are very similar.
3.3 Global Harmonization Task Force The Global Harmonization Task Force was founded in 1992 by voluntary participation of members from the medical device regulating bodies of Canada, the United States, Japan, the European Community and Australia [10]. The goal of the Global Harmonization Task Force Proc. Instn Mech. Engrs Vol. 217 Part H: J. Engineering in Medicine
is to examine existing medical device regulation and determine what areas are appropriate for harmonization. Harmonization of medical device regulation would eliminate trade barriers between countries and encourage consistent global standards of care. To date, the four working groups of the Global Harmonization Task Force have produced 16 nal documents covering the areas of pre-market submission and labelling requirements, post-market vigilance and adverse event reporting systems, quality system requirements and quality systems auditing practices. It is unclear whether any of the nal documents have been accepted or implemented by medical device regulating bodies.
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DISCUSSION AND SUMMARY
This article has described the process of legally marketing medical devices in Canada and for export to the United States and Europe. It can be seen that the Canadian, American and European systems of device regulation have a number of similarities. Perhaps the most notable dierences were the contrast between the Canadian and American pre-market notication processes, particularly the 510k process of the US that has no Canadian equivalent. The 510k application process has been cited as having a positive impact on the medical device industry by reducing time to market of medical devices. However, it has also been cited as a potential impediment to innovation in the medical device industry by discouraging the introduction of novel technologies through added development costs. Typically, the relatively new approval process for devices in Canada is a long process and tends to be frustrating to manufacturers of medical devices.
REFERENCES 1 Therapeutic Products Programme. Guidance for the riskbased classication system. Guidance Document GD006/RevDR-MDB. http://www.hc-sc.gc.ca/hpb-dgps/ therapeut/htmleng/guidmd.html, 1998. 2 Therapeutic Products Programme. Guidance on how to complete the application for a new medical device licence. Guidance Document GD013/Rev00-MDB. http://www. hc-sc.gc.ca/hpb-dgps/therapeut/htmleng/guidmd.html, 1998. 3 Therapeutic Products Programme. Management of applications for medical device licences and investigational testing authorizations. http://www.hc-sc.gc.ca/hpb-dgps/ therapeut/htmleng/guidmd.html, 1998. 4 Therapeutic Products Programme. Draft policy on recognition and use of standards under the medical device regulations. http://www.hc-sc.gc.ca/hpb-dgps/therapeut/ htmleng/guidmd.html, 1998. 5 Orion Canada, Inc. Quality system requirements for H05502 © IMechE 2003
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medical devices: Reference guide for manufacturers selling medical devices in Europe, Canada and the United States. Prepared for Life Sciences Branch of Industry Canada, 2001. 6 Fries, R. C. Reliable Design of Medical Devices, 1997 (Marcel Dekker, Inc.). 7 Monsein, L. H. Primer on medical device regulation. Part I—history and background. http://www.rsna.org/ REG /research/regulatory/wfprfc.html, 2001.
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