Approval of medical implants according to the European Medical Device Regulation (MDR)

CE-Certification

The CE mark is a prerequisite for launching a new implant in the EU. Before marketing, a manufacturer must first and foremost prove that the implant is safe and efficient and has a positive benefit-risk ratio. A notified body tests and certifies this proof. Only then may the manufacturer affix the CE mark and place the implant on the market. With regards to the requirements under medical device law, the following essential steps can be differentiated on the way to placing a product on the market and the downstream market phase: 1. qualification of the implant as a medical device; 2. risk classification of the implant; 3. manufacturer’s obligations; 4. product requirements; 5. declaration of conformity; 6. CE marking; 7. registration and 8. Monitoring [3].

Qualification of the implant as a medical product

The manufacturer must first determine whether their implant is a medical product as defined in Art. 2 (1) MDR on the basis of its intended purpose. Other characteristics of a medical device are that it is intended for use in humans, its principal action takes place in or on the body, and that this is not achieved by pharmacological or immunological means or metabolically. If the implant in question is a medical device, both the device and the manufacturer are subject to the provisions of the MDR. It should be noted that the scope of the MDR now also includes products without a medical purpose, such as coloured contact lenses or implants and substances for aesthetic purposes. The further text of the MDR does not speak of “implant”, but of “implantable device”, which is defined in Art. 2 (5) MDR as follows: “a device, even if it is intended to be completely or partially absorbed, which is intended to be completely introduced into the human body by a clinical intervention or to replace an epithelial surface or the surface of the eye and to remain there after the intervention. An implantable device also means any device that is intended to be partially introduced into the human body by clinical intervention and to remain there for at least 30 days after the intervention.” [3]

Risk classification of the implant

Manufacturers must classify their medical devices into classes I, IIa, IIb and III, taking into account the intended purpose and the associated risks (Art. 51 MDR). The risk class is the basis for the further steps up to CE marking, in particular for the choice of the conformity assessment procedure and for the scope of the clinical evaluation. Under the previous European regulatory framework, implants were classified according to Annex IX of Directive 93/42/EEC supplemented by Directive 2007/47/EC. In the body periphery, implants were generally assigned to Class IIb and, for the cardiac, central circulatory and nervous system site of application, to Class III [4]. Directives 2003/12/EC and 2005/50/EC specified Class III classification for breast and joint implants. An exception were denture implants, which were assigned to Class IIa. Guidance for the classification of medical devices according to MDR is provided by the MDCG Medical Device Coordination Group Guideline 2021-24 [5]. This also contains examples of risk classes assigned in each case.

If the manufacturer uses software that controls or influences the use of an implant and neither has its own medical purpose nor generates independent information for a medical purpose, MDCG Guideline 2019-11 must be observed for both qualification as a medical device and classification [6]. In Annex I e) of the study under consideration, a web system for monitoring pacemakers or implantable cardioverter defibrillators is given as an example, which falls within the regulatory scope of the MDR. Of particular importance in connection with the classification of software is, above all, implementation regulation 3.3 in Annex VIII MDR. This states that software that controls a product or influences its use is considered to be in the same class as the product, whereas software that is independent of other products is classified on its own [3].

Manufacturer’s obligations

Regardless of the risk class and type of medical products, all manufacturers are subject to the obligations set forth in Art. 10 MDR. Some of these include fulfilment of essential safety and performance requirements; establishment, documentation, application, maintenance of a risk management system; performance of clinical evaluation including clinical follow-up; preparation and continuous updating of technical documentation; performance of a conformity assessment procedure (including product classification) and preparation of an EU declaration of conformity; establishment of a unique device identification (UDI) system and all necessary registrations of devices and the manufacturer, etc.

Quality management

Manufacturers of medical devices must establish, document, apply, maintain, continuously update and improve a quality management system (QMS). The application of the relevant standard EN ISO 13485 allows manufacturers to implement the legal requirements as far as possible as well as other aspects of the QMS in a meaningful way.

Risk Management

Manufacturers of medical devices must establish, document, apply and maintain a risk management system. The EN ISO 14971 standard is the central standard for the risk management of medical devices. It explains how the corresponding process must be set up and maintained in detail.

Clinical evaluation and testing

The clinical evaluation of medical devices aims to assess and demonstrate the clinical safety and performance of the medical device based on clinical data (Art. 61 and Annex XIV Part A, MDR). The type and scope of this evaluation depend on the intended purpose defined by the manufacturer.

Part of the clinical evaluation is also a post-marketing clinical follow-up (Art. 61 (11) and Annex XIV Part B, MDR).

For implants, clinical trials to generate clinical data are, with some exceptions, mandatory (Art. 61 (4), MDR). The exceptions to this regulation are very narrowly defined. Although it is possible to use data from similar products for clinical evaluation, this has been made considerably more difficult with the introduction of the MDR [7]. Art. 61 (5), MDR also states that even in the case of proven similarity of two class III devices or implants, both manufacturers need a contract that explicitly grants full access to the technical file to the manufacturer of the second device on an ongoing basis.

The provisions for clinical investigations of medical devices in the MDR are very comprehensive and are regulated in Articles 62-82. To support the manufacturers, the EU Commission has published an FAQ list on the subject (MDCG 2021-6, [8]). The type of clinical trial that the manufacturer must choose essentially depends on whether the medical device is CE-marked, used within its intended purpose, or whether additional invasive or patient-invasive procedures are used. The MDR basically distinguishes between three types of clinical trials:

• Clinical trials for conformity assessment according to Art. 62,
• Clinical trials for clinical follow-up according to Art. 74(1), and
• Other clinical trials according to Art. 82.

Information on the safety and performance of the product

According to Art. 39 of the MDR, the legislator writes: “Patients who are implanted with a device should be provided with understandable and easily accessible background information that identifies the implanted device, as well as other relevant information about the device, including any necessary warnings about health risks or precautions that may need to be taken, for example, reference to possible incompatibilities with certain diagnostics or with safety scanners.” This is to be achieved through information on the labelling, packaging and in the instructions for use, as well as through the new implant card.

New for manufacturers is the requirement in the MDR included in Article 18 “Implant card and information to be supplied to the patient with an implanted device “. However, the implant card (IC) is not required for “simple” implants such as sutures, staples, dental fillings, etc. The MDCG published the 2019-8 guidelines for the implementation of Article 18 and 2021-11 on product types [9], [10]. According to the 2019-8 guideline, implant cards should be used for patients to be able to identify the respective implant and to have access to information related to the product, e.g., published in the European database EUDAMED. In addition, patients should be able to identify themselves as requiring special treatment in specific situations, e.g., during security checks. Finally, in emergency situations, the ICwill allow clinical staff or first responders to be informed about the special needs and also precautions to be taken when handling patients.

Technical documentation

The technical documentation is a compilation of all relevant documents of a product. It must be kept up to date during the entire product life cycle. The components of the technical documentation include six essential chapters: 1. product description and specification, 2. information to be supplied by the manufacturer, 3. design and manufacturing information, 4. safety and performance requirements, 5. benefit-risk analysis and risk management, and 6. product verification and validation [3].

Responsible person

Each manufacturer must designate a person responsible for regulatory compliance (Art. 15, MDR). This person must be specially trained and is responsible for [11]:

• The conformity of the medical devices with the regulatory requirements,
• the technical documentation and the EU declaration of conformity, and
• the market surveillance.

These responsibilities must be mapped accordingly by the manufacturer in the processes of the QMS.

Product requirements

The product range of implants is very wide. It includes passive and active implants with application in different body regions for a different duration. In addition, active implants may require control software and programming devices. Therefore, only some of the basic safety and performance requirements for implants are explained below as examples, which may not be applicable to every product in individual cases.