Manufacturers in the global medical market face a complex maze of worldwide regulatory requirements. Regulating medical devices in many countries is a combination of national and independent standards, so things can get confusing. But developing international standards supports global commerce, eases the burden on manufacturers to comply, and helps ensure that users receive safe medical devices.

Standards organizations

The first general standards body was the British Standards Institution (BSI). Today, there are more than 100 standard-setting organizations. In the U.S. these include the American Society for Testing and Materials (ASTM) and the American National Standards Institute (ANSI). ANSI is the sole U.S. member of the International Organization for Standardization (ISO) and the International Electrical Commission (IEC). One of its primary duties is to accredit U.S. technical advisory groups and promote U.S. policy.

Developing standards for medical devices began with the Medical Devices Act of 1976, which gave the FDA control over regulating medical devices. Over the past thirty years, these standards have evolved to address increasingly complex devices. More recently, the European Union (EU) and other governments have issued regulations on medical devices, leading to a need for international standards.

In the U. S., the EU, Canada, and other countries, regulating medical devices involves both national standards and those written and maintained by independent organizations.

Developing and approving a standard begins by circulating a draft from a designated working group or technical committee. The prefix “DIS“ identifies international standards in a draft stage. Draft European standards carry the prefix “prEN.“ After circulating a draft for public comment, it is submitted for formal vote and, if it passes, is released for publication.

Harmonized Standards

Two European Standards Organizations , the European Committee for Standardization (CEN) and the European Committee for Electrotechnical Standardization (CENELAC), determine the technical specifications medical-device manufacturers must meet to sell in the EU. Since 1987, more than 25 total Directives, or European regulations, have come into force.

“Harmonised standards“ are European versions that have been published in the Official Journal of the European Union and adopted by CEN and CENELAC after input from the European community. The three standards that govern the sale of medical devices in the EU are 90/385/EEC, Active Implantable Medical Devices, 93/42/EEC, General Medical Devices, and 98/79/EEC, In Vitro Diagnostics Medical Devices.

For instance, EN 60601-1-2, Electromagnetic Compatibility of Medical Electrical Equipment, is a harmonized standard listed under 93/42/EEC. Electromagnetic compatibility testing is critical in demonstrating that products are safe and do not interfere with other devices in use nearby.

Although conformity to harmonized standards is critical to placing medical devices on the EU market, using the standards is not mandatory. But applying them during medical-device design and manufacture does provide a presumption that essential requirements have been satisfied.

ISO Standards

ISO standards of particular note that influence the design of globally distributed medical devices include EN ISO 13485:2003 - Medical devices - Quality Management systems - Requirements for regulatory purposes, which deals with establishing a quality system used for medical devices. The other is ISO 14971:2000 - Medical devices- Application of risk management to medical devices. The European Directives offer several routes for compliance to ISO standards. These include options for full quality assurance, which is interpreted to mean conformity to EN ISO 13485. Canadian regulations actually require conforming to the current version of ISO 13485. Recently, Japan and Australia recognized ISO 13485 and ISO 14971. The latter specifies a procedure for manufacturers to identify and control hazards associated with medical devices.

Organizations approved by various governments perform audits to check for conformance to the required ISO quality system and risk-management standards. In Europe, the regulatory agency, or Competent Authority, of each member state of the European Economic Area ensures companies meet directive provisions. To do this, they notify third-party organizations, referred to as Notified Bodies, to perform conformity audits. Because of differing expertise, not all such bodies can perform conformity-assessment procedures for products or quality systems against all medical directives.

For Canadian standards, certification by a Canadian Recognized Registrar demonstrates compliance. Fortunately, most registrars are also Notified Bodies and one audit can yield certification to both the Canadian Medical Device Regulation and the applicable EU directive. A list of the registrars recognized in Canada can be found at www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/lr_rev0_e.html. Many other countries also recognize third-party registration to EN ISO 13485.

Process and system standards

In addition to general standards, there are a myriad of standards specific to processes and system safety. Process standards include those for sterilization of devices by radiation, ethylene oxide, and steam. Standards also specify how statistical sampling is done. Still other standards specify safety requirements for specific medical devices. ISO 60601, for instance, is a series of standards that detail the requirements for electrical safety for devices coming into contact with patients. ISO 60601-1 covers general requirements for basic safety and performance. ISO 60601-2-34 has requirements for invasive blood-pressure monitoring equipment.

Companies must meet these internationally recognized standards and, in most cases, demonstrate conformance to them. This is often done for process standards during a quality-system inspection or as part of the application for registering a new product.

Conformance to safety standards is usually done by testing to the specifications detailed in the standard. For instance, ISO 10993 series has detailed information on required biocompatibility testing based on device and duration of contact. It also references specific test methods and acceptance criteria.

Device testing can be done in-house. But manufacturers lacking necessary expertise can enlist an accredited laboratory that is certified by government agencies. Examples of accrediting agencies include the Occupational Safety and Health Administration, the National Institute of Standards and Technology, and the Statistical Society of Canada. Independent organizations such as the International Electrotechnical Commission for Electrical Equipment and the American Association for Laboratory Accreditation also certify testing laboratories. However, manufacturers should make sure that the laboratory is accredited for the testing to be conducted and by an agency recognized in the geographic area in which they plan to distribute products. Fortunately, most accrediting bodies are internationally recognized.

Adopting national standards

Although many standards are voluntary in principle, it is difficult to find alternate routes to demonstrate the expected safety requirements. In fact, conforming to recognized standards is usually a requirement. Take EN ISO 13485, for instance, which has been incorporated into law. (In Europe, individual countries often officially adopt standards, particularly ISO standards. The “EN“ country code in front of EN ISO 13485 means the EU has adopted the standard.)

The German Institute for Standardization (DIN) is the recognized standards body in Germany. Thus, DIN EN ISO is the German edition of an ISO standard and is used as a European standard. Similarly, the British Standards Institution (BSI) is the UK's national standards body. All European standards fall in line with British standards so a BSI EN ISO 13485:2003 is equivalent to EN ISO 13485.

International Standards and the FDA

The FDA recognizes more than 400 international standards. In the “Least Burdensome Approach,“ which was part of a 1997 FDA reform, using recognized standards was deemed a reasonable approach to meeting requirements. A recognized standard may be any international or national standard that corresponds to regulations and devices defined in the Code of Federal Regulations. Recognized standards are evaluated by the FDA and recognized by being published in the Federal Register.

Recognized standards cover a variety of requirements for sterilization and biocompatibility, for example, and may be specific to devices such as dental instruments, orthopedic implants, and coronary stents. A searchable database of FDA-recognized standards is available on the FDA website at www.fda.gov.

The FDA has also published many documents that guide manufacturers through regulatory submissions. Although documents may call out a specific standard, its use is voluntary. However, manufacturers certifying that their devices meets a standard must maintain appropriate records to demonstrate compliance. And manufacturers not using the standards must be able to show alternative methods and expected results.