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by Tamas Borsai, Brian Ludovico, and Gregor Dzialas

The medical device industry considers compliance with the European Union's Medical Devices Directive a passport to the European market. Not to be overlooked, however, is the global appeal of ISO 13485—"Medical devices—Quality management systems—Requirements for regulatory purposes." Although ISO 13485 doesn't take the place of the EU's MDD, or those of other countries, this regulatory standard assures authorities that a manufacturer of medical devices has developed and implemented a quality management system. As companies expand into other markets, they find that ISO 13485 lends itself to conformance requirements across the globe.

The 27 members of the European Union, Canada, and Turkey open their markets only to medical device manufacturers that have complied with ISO 13485. By comparison, the United States enforces its own national regulations regarding medical devices, as with the Food and Drug Administration's CFR 21 Part 820. These regulations share several similarities with ISO 13485's quality system requirements. In fact, upon review, medical device regulations being implemented around the world contain many of the same requirements as ISO 13485. It stands to reason that ISO 13485 is a practical solution for those who plan to sell their products on the global market.

The case for ISO 13485
Some manufacturers want an ISO 13485 certificate in hand as proof of their products' quality. Others may choose to focus solely on obtaining a CE Mark (an EU safety-compliance mark that covers a variety of products, including medical devices) in an attempt to reduce time-to-market and eliminate redundant spending. Such an option can prove more costly than anticipated. As a regulatory standard, ISO 13485 can strategically position a manufacturer to adapt to new market requirements worldwide.

Several manufacturers prefer to undergo ISO 13485 certification well before they have a commercial product on the market. This strategy uses the formalized standard as a management tool to make sure that processes are under control from the beginning. For these companies, quality no longer becomes a promise but a fact ensured by their system and confirmed by an independent assessor.

Having a quality management system at an early stage provides another advantage to these companies: quicker market access. Many regulatory organizations were involved in the development of this standard. Therefore, requirements in regulatory laws such as the 93/42/EEC MDD share numerous similarities with ISO 13485. Hence, after a simple update of their systems, these companies can quickly and cost-effectively seek regulatory approvals from a variety of countries.

For medical device manufacturers, it is mission-critical to receive such certification quickly. They invest in both research and development, and in the product's sales and marketing plans. Particularly in the medical device industry, the longer a product languishes in the review process, the less it returns to the manufacturer's bottom line.

ISO 13485 certification is a strategic choice to help meet regulatory requirements within Canada, Japan, Europe, and Australia. We will take a brief look at some of these regulatory programs and how they relate to ISO 13485.

European Union: MDD
The approval and marketing of medical devices are regulated by three European Union directives: 90/385/EEC Active Implantable Medical Devices, 93/42/EEC Medical Devices Directive, and 98/79/EEC In Vitro Diagnostic Devices. Each of these directives requires manufacturers to have a quality management system in place before a product can be released into a member's market. Currently, these directives are under review for updates because they were implemented more than five years ago.

A draft of the new revision for the MDD was published in 2005, and the expectation is that the European Union will implement it by the end of 2007. The most significant proposals concern conformity assessment, including:

Design documentation and design review

Clarification of the clinical evaluation requirements

Post-market surveillance

Compliance of custom-made device manufacturers

Alignment of the original MDD 93/ 42/EEC


At this time, no changes to ISO 13485 are imminent. It is still a valid certification to hold even as changes to the MDD are being made. This standard outlines a quality system for the medical device industry and creates a map for manufacturers planning international distribution. In effect, ISO 13485 creates an easy-to-understand blueprint to help implement and maintain a quality system.

Canadian Medical Devices Regulations
In 1998, the Food and Drugs Act was put into effect through the CMDR. Many of these regulations are similar to those of the United States and the European Union, such as mandatory reporting timelines for complaint handling. Under the CMDR, manufacturers are required to obtain device licenses for products that they intend to sell in the Canadian market. To apply for such a license, manufacturers must submit a copy of a quality management system certificate showing conformance to ISO 13485.

To issue these quality management system certificates, the CMDR dictates that "persons" (i.e., registrars) must be recognized under the Canadian Medical Devices Conformity Assessment System. When accredited under CMDCAS, these registrars ensure that the regulations are woven into the fabric of the manufacturer's quality management system.

Manufacturers often find value in the standard's de-- tailed explanation of how to maintain a management system. Because ISO 13485 is designed for regulatory purposes, it provides an effective conduit for implementing the device regulations. The acceptance and integration of ISO 13485 into regulatory requirements is seen throughout various memoranda of understanding between Canada and other regions, such as the European Union and Australia-New Zealand, creating a shorter path to global harmonization.

Japan: Pharmaceutical Affairs Law and Ministerial Ordinance 169
In recent years, Japan has updated its system for medical devices to account for the global harmonization of regulations and safety measures. In 2005, the PAL was revised, mandating that all medical device manufacturers receive approval before market entry. These changes mirror current regulatory approaches already in place in Europe and Canada. In fact, the Ministry of Health, Labor, and Welfare based Japan's quality management systems requirements on ISO 13485 and outlined them in Ministerial Ordinance 169.

In addition, by incorporating the guidance documents of the Global Harmonization Task Force, Japan can harmonize its requirements and reduce some conflicting demands placed on manufacturers because of the variety of individual countries' market entrance requirements, such as adverse event reporting, post-market surveillance, and auditing practices. The GHTF is a voluntary group composed of national medical device regulatory authority representatives from North America, Europe, and Asia-Pacific. The aim of GHTF is to encourage common practices while ensuring the safety and efficacy of medical devices.

PAL regulation has a requirement for Class II, medium-risk devices (or so-called "controlled medical devices") that parallels ISO 13485. For these products, a registered certification body (RCB) must perform an on-site evaluation of the company. Some RCBs, like TÜVRheinland, are also accredited as notified bodies in the European Union or CMDCAS-recognized registrars in Canada, making global access more convenient for manufacturers. For manufacturers simultaneously seeking approvals in Japan and the European Union, RCBs can perform a combined audit to meet both Ordinance 169 and ISO 13485 requirements.

Australia New Zealand Therapeutic Product Authority
In December 2003, Australia's Therapeutics Goods Administration and New Zealand's Medicines and Medical Devices Safety Authority (MEDSAFE) agreed to establish a joint regulatory scheme for therapeutic products. This trans-Tasman regulatory scheme is now overseen by the ANZTPA. The agency oversees the quality, safety, and effectiveness or performance of medical devices as it relates to the products' manufacture, supply, import, export, and promotion.

Currently, there are a number of medical- device-related international agreements between Australia's Therapeutic s Goods Administration and their counterparts in other countries. These include a Mutual Recognition Agreement with the European Union, Memoranda of Understanding with both Canada and Switzerland, and other agreements with countries such as Japan, China, and Malaysia.

In addition, there is a limited agreement with the United States that currently does not include medical devices but is in the informal discussion phase. The existing Therapeutic Goods (Medical Devices) Amendment Act (2002) is modeled on the recommendations of the GHTF.

In May 2006, a consultation draft of the Australia New Zealand Therapeutic Products Regulatory Scheme (Medical Devices) Rule 2006 was published by the Minister for Health and Aging in Australia and the Minister of Health in New Zealand. In many ways, this proposal shows similarities to the basic principles found among other medical device regulations—because of the GHTF model.

Under the current MoU with Canada, manufacturers located in Australia, New Zealand, or Canada will be able to take advantage of similarities among their regulatory schemes for market access. Hence, it is anticipated that those medical device manufacturers that implement ISO 13485 will have a good starting position in this part of the world when the proposed regulations are passed.

United States: Quality System Regulations 21 CFR Part 820
ISO 13485 certification is not recognized under the FDA's Food, Drug, and Cosmetic Act as sufficient evidence of compliance with U.S. Quality System Regulations (QSReg). However, QSReg 21 CFR Part 820 does share many similarities with ISO 13485. In fact, compliance with ISO 13485 can help manufacturers maintain compliance with the U.S. QSReg. The parallels between both regulations were instrumental for the FDA's Third Party Inspection Program, which was introduced by the Medical Device User Fee and Modernization Act of 2002.

Under this program, eligible manufacturers of Class II and III medical devices can choose an FDA-accredited third party instead of an FDA official to perform inspections. The primary benefit of this voluntary program is to combine FDA inspections with other conformity assessment inspections to save time, money, and resources.

Initially, 15 quality system registrars and notified bodies were accredited by the FDA to perform independent inspections. An accredited person can perform a side-by-side inspection to assess compliance with the MDD, ISO 13485, effective implementation of Part 1 of the CMDR, and QSReg 21 CFR Part 820.

Fortunately, this new worldwide third-party inspection was widely accepted by European accreditation bodies. They had previous experience with combination inspections because of agreements between the United States and Europe. However, the Canadian accreditor, Health Canada, saw a need to prove the validity of combination inspection to ensure the same level of confidence in the inspection results.

In September 2006, the United States and Canada established a Pilot Multipurpose Audit Program. In this pilot, qualified auditing organizations can perform a single inspection for both Health Canada and the FDA. PMAP evaluates the effectiveness of performing a single third-party inspection and/or audit of medical device manufacturers' quality systems and gauges whether they meet the needs and regulatory requirements of both countries.

This combined auditing and inspecting strategy accommodates the ever-increasing efforts in regulatory harmonization and incorporates quality system requirements found in both the QSReg and ISO 13485.

ISO 13485 certification process
As global market access becomes paramount, manufacturers begin to focus more on a clear regulatory picture. A quality management system must incorporate a company's processes to meet the requirements of ISO 13485. This enables an auditor to compare the standard's requirements with the company's standard operating procedures and actual performance of those procedures.

Manufacturers considering ISO 13485 are recommended to contact a regulatory organization that has a wide scope of accreditation to better fulfill all regulatory needs. In some cases, it may also be helpful to have a consultant or in-house expert review and implement the requirements in preparation for a regulatory assessment.

After a quality management system has been implemented, an auditor can perform an on-site audit, taking into account the various locations where quality system operations are performed, including the locations of critical subcontractors such as sterilization organizations and original equipment manufacturers. Auditing subcontractor sites is becoming more prevalent as outsourcing is used for cost-controlling measures. With objective evidence of the manufacturer's compliance to both standard and regulatory requirements, the auditor can then give either a positive or negative recommendation for certification.

Countries in North America, Europe, and Asia have differing sets of compliance rules. However, one common denominator can be found with ISO 13485. This standard is widely regarded as proof of a quality management system in the medical device industry. It outlines a set of processes and confirms a level of performance that validates a manufacturer's quality management system. In markets worldwide, ISO 13485 can therefore be considered a smart, fast, and cost-effective path to your next product launch.

About the authors
Tamas Borsai is division manager of TÜVRheinland's Medical Division in Newtown, Connecticut. Since 1990, Borsai has worked for the company's Material Testing and Medical Divisions in Europe, Asia, and North America. He has a bachelor's degree in electrical engineering from the Institute of Power Engineering of the Kandóό Kálmán College in Budapest, Hungary.

Brian Ludovico is senior technical manager and certification officer at TÜVRheinland's Boxborough, Massachusetts, office and manages the company's CMDCAS program. Ludovico has 16 years of experience in the medical device industry, including four years at U.S. Surgical Corp. He holds a bachelor's degree in biology from the University of Connecticut.

Gregor Dzialas is FDA third-party audit program manager and certification officer at TÜVRheinland's Boxborough, Massachusetts, office. Dzialas has 14 years of experience in the medical device industry, with an expertise in FDA third-party inspections. He holds degrees in biology from the University of Cologne and biomedical engineering from Technical University Giessen-Friedberg.