Any medical device manufacturer seeking to enter the European market will need to use the services of a notified body in its quest to obtain CE marks for its products, which allow those products to freely circulate throughout the European Union (EU). To receive a CE mark, a device has to be in compliance with the requirements of the relevant EU directive, with a particular emphasis on the essential requirements for safety and performance.
The three European directives related to medical devices are: the Medical Devices Directive 93/42/EEC (MDD) as amended in directives 2000/70 and 2001/104 on medical devices incorporating stable derivatives of human blood or human plasma; the Active Implantable Medical Devices Directive 90/385/EEC; and the In Vitro Diagnostic Medical Devices Directive 98/79/EEC.
The methods a manufacturer can use to demonstrate that its devices comply with applicable requirements vary depending on which directive applies and on the devices' classification. The annexes of the directives define various available conformity assessment procedures. A notified body is used by the device manufacturer to perform the functions defined in the annexes. (Each notified body may be restricted to handling specified types of devices or annexes.) But what, exactly, is a notified body?
A notified body is an organization accredited by a national authority of an EU member state and recognized by the EU to audit quality systems, test devices, and assess technical documentation to confirm that manufacturers and their products meet applicable directives (e.g., the MDD for medical products) and standards (e.g., ISO 13485 on quality systems). Upon the successful completion of an audit, device-testing project, or assessment of a design dossier, the notified body issues a certificate or assessment report that confirms compliance with applicable European laws.
It is important to understand the difference between a notified body and a registrar. A notified body is authorized to issue CE certificates and to conduct ISO 13485 quality system audits. While a registrar is also authorized to perform ISO 13485 audits, it cannot issue a CE certificate. All notified bodies are registrars, but not all registrars are notified bodies. Typical activities performed by a notified body include the following:
- Full quality assurance. The notified body assesses the manufacturer's quality system by performing sampling across a range of products and processes to ensure that requirements are met.
- Design examination. The notified body assesses the design dossier for an individual product to ensure that it is in compliance with the essential requirements.
- Type examination. The notified body assesses the technical documentation (technical files) for all of a manufacturer's products and also performs actual product testing.
- Production and product quality assurance. The notified body performs an assessment of either the manufacturer's quality system covering production and inspection (production QA) or final inspection (product QA). Sampling is performed across the range of products to ensure that relevant technical files are available and relevant processes are undertaken to meet requirements.
There are currently about 85 notified bodies accredited for the MDD. Device manufacturers can use the services of any of these notified bodies to carry out the desired conformity assessment procedure for their products, regardless of the member state in which the notified body is established. Member states must accept into their national markets products that have been assessed by foreign notified bodies. And, notified bodies must accept CE assessments from other notified bodies, which is important because it allows CE certificates to be transferred.
Notified Body Selection Criteria
Table I. (click to view the full table)
A detailed matrix of criteria that a company might use to choose a notified body (NB), listing examples of how these criteria might be fulfilled by different notified bodies.
Notified bodies are consultants and contractors to companies. Accordingly, they operate under a formal contract and are paid a fee for their services. The evaluation of a notified body should involve more than a cursory evaluation of pricing, however. A medical device manufacturer should devote careful consideration to the selection process, because the company will likely continue to employ the services of the notified body for many years to come.
Accreditation and Experience. The most important criterion when choosing a notified body is its accreditation to certify all of the types and classes of products that the manufacturer plans to place on the European market. Brand accreditation is important if the company offers medical devices ranging from Class I to Class III, and even more so if it also manufactures combination products in which devices are combined with tissue, blood-derived products, or medicines. Obtaining a CE mark for a drug-device combination product requires consultation with one of the European drug agencies, so using a notified body that has experience with this procedure can be beneficial.
Determining whether a combination product can be considered a medical device that falls under the MDD requires expertise and experience. The outcome of this determination could be critical to successful market entry. For example, review time required by the notified body might be measured in months if the product is considered a device, compared with years if it is judged to be a drug-device combination. Not only would it take less time to bring a device to market, but the costs accrued during the approval process would be reduced.
The fundamental criterion used to make the distinction between a medical device and a combination product is the principal mode of action. For medical devices, the principal mode of action is mechanical, whereas drug-device combination products also have a pharmacologic, immunologic, or metabolic action. Only drug-based products are absorbed, distributed, metabolized, and excreted by the body.
Some medical products might use materials of animal origin during the manufacturing process, in which case they might be classified as Class III. Such animal-origin products require that the notified body assess the design dossier and consider the requirements of Directive 2003/32/EC, the so-called transmissible spongiform encephalitis (TSE) directive. A specific risk management scheme must be adopted for products falling within the scope of this directive.
After the notified body prepares its summary evaluation report for such a product, its country's national regulator of materials of animal origin seeks the opinion of the other member states regarding the assessment report before a CE mark can be granted. As is the case for drug-device products, time and cost savings may be realized if the notified body is familiar with this process.
A notified body's willingness to share its experience with best-practice approaches in the market can also be beneficial for the manufacturer, as can a notified body's offer of in-depth training. Providing firsthand information to manufacturers enables them to understand the notified body's specific interpretation of rules, regulations, standards, and general requirements. In addition, not all notified bodies have the same level of influence within the notified body working group or the same level of standing with individual national competent authorities. Manufacturers should be aware of such differences and choose a notified body that is well recognized and can be expected to successfully defend a position in front of another notified body or a competent authority in the event that its findings are challenged.
Size and Staffing. Generally speaking a notified body with a broad range of accreditation can fulfill a device manufacturer's needs for future product development activities. All of the large notified bodies have experience with certifying combination products as well as devices of various types and classes. But is bigger always better?
Smaller notified bodies, although often able to deliver excellent service in a timely manner and for a low price, may have limitations if confronted with highly specialized products. Also, they might not be a good choice if a manufacturer's future plans involve expansion to Japan or Canada, where special accreditation for the notified body is needed. Not all notified bodies have a global presence, and some might not be able to assist with services supporting a required certification in certain markets. The availability of regional auditors can also be a significant factor in keeping auditing budgets under control, because travel costs can add up quickly. Some small notified bodies work with partners in other countries and most of the time such relationships are seamless, but the manufacturer, as a customer, will then have to interact with two (or more) separate entities, which adds complexity and raises the possibility of problems.
When choosing a notified body, manufacturers also need to consider the organization's staffing policies. Having a project manager at the notified body can help keep lines of communication with the manufacturer open. A project manager is charged with ensuring that all of the services agreed to by the manufacturer and the notified body are performed and documented. He or she facilitates interaction among departments and experts within the notified body.
The availability of dedicated assessors for the review of technical files and design dossiers can be the determining factor in whether a project's agreed-upon timeline can be achieved. Many notified bodies do not have dedicated resources for file assessment, which frequently leads to situations in which the person who is scheduled to assess a product may need to spend several weeks on an auditing tour. This can delay issuance of the desired certificate.
It is equally important that an assessor have an opportunity to accompany a lead auditor from time to time during the audit of a company for which he or she is assessing technical documentation. Only in this way can the assessor gain sufficient insight into a company's systems and a solid understanding of how procedures described in the documentation are performed on the production line. These audits can also help to increase the notified body's level of trust in the company and its systems.
When contracting with a notified body, dealing with a certain level of bureaucracy cannot be avoided. Therefore, a manufacturer choosing a notified body should consider its internal organization and approval processes. Frequently, delays in issuing the certificates can be caused by the fact that a central certification board has to grant final approval after an assessment has been completed. When boards do not meet frequently, delays become inevitable. To avoid such backups, some notified bodies use a certification manager rather than a board.
Managing Product Changes. Confusion can arise from a lack of clarity regarding whether some product improvements or added codes require approval of an updated certificate before implementation. Some notified bodies have guidance documents available that can help manufacturers avoid false expectations and prevent unfortunate surprises. In addition, there are notified bodies that do not explicitly list product codes on CE certificates (other than Class III certificates); the link between the certificate and the product code is the Declaration of Conformity, which is under the control of the manufacturer. With such a system, new codes that fall under the scope of an already existing certificate can be added easily, and no time will be lost by waiting for the receipt of an updated certificate or attachment.
Other notified bodies allow matrix certificates, which contain the critical product parameters and the limits of those parameters. Any new product that falls within the scope of a matrix certificate and has specifications that fall within the defined limits of the critical parameters will automatically be considered covered by the certificate. Examples of critical parameters include product performance specifications and indications for use.
Changing Notified Bodies
As stated earlier, a manufacturer can use any notified body in the EU as long as that organization is accredited to carry out the desired conformity assessment procedure for a particular product. This flexibility to choose any notified body also includes the option to change from one notified body to another and to shift CE certificates from the former notified body to the new one.
Ideally, a manufacturer's relationship with a notified body will be maintained for many years. Although the requirements for placing medical devices on the European market are the same for all manufacturers and notified bodies, there are differences in interpretation of requirements and individual preferences regarding the format of documentation, frequency and content of notifications, and other more formal and practical aspects of the relationship between a manufacturer and a notified body. All of these elements make it beneficial to continue to work with the original notified body of choice once the business relationship has been established.
In today's world of acquisitions and mergers, however, a company might benefit from limiting the number of notified bodies with which it has contracts. Doing so can help limit the number of internal formal procedural requirements and audits that have to be performed on an annual basis by a notified body. It also ensures more consistent opinions and interpretations of the requirements of laws, directives, and standards. In addition, because notified bodies make their living, so to speak, from the fees they charge to manufacturers, a limited number of notified bodies may help a manufacturer increase its importance and stature as a customer, which might increase the attention and service level provided by the notified body.
Many notified bodies have defined procedures on how to transfer CE certificates from one notified body to another. A transfer typically involves an evaluation of the existing CE certificate and the most recent assessment report by the future notified body. Additional audits might be required, but these will typically be conducted at the time when the next periodic audit was previously scheduled. As a consequence of changing to a new notified body, a revised Declaration of Conformity will have to be issued, and the product labeling will have to be revised to reflect the new notified body's reference number.
As well as limiting the number of notified bodies it uses, a company that has undergone acquisitions or mergers should consider centralizing ownership of its CE certificates at the legal entity that is in charge of complying with global regulations. Doing so helps to reduce the number of required audits performed at various company sites and facilitates consolidation of processes and internal requirements.
Device manufacturers planning to market their products in the EU should carefully identify their own needs as well as the capabilities of the notified bodies under consideration before entering a contractual relationship with such a body. Without question, the accreditation that a notified body has to assess a company's current and planned devices is the most important criterion to consider, followed by the notified body's experience with such products.
Other criteria include the notified body's willingness to share its expertise with the manufacturer, its size and global presence, and its use of dedicated project managers and assessors. It is also important that the notified body has clear policies on handling product changes. Carefully choosing a notified body can save time and money, and increase a company's chances for successful market entry.
Stefan Menzl is the director of regulatory affairs, compliance, and clinical research for Advanced Medical Optics Inc. in Europe, Africa, and the Middle East. He can be reached at [email protected].