The team of KIELTYKA GLADKOWSKI dedicated to clients operating in life science sector actively advises on all aspects of in vitro diagnostics, including regulatory, corporate and investments matters. For the purposes of such clients this text analyses the bullet points of REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Regulation 2017/746/EU (IVDR) replaces the existing Directive 98/79 / EC on in vitro diagnostic medical devices (IVDD), which was adopted in 1998.
With the publication of the IVDR, the five-year transition period from the In Vitro Diagnostic Medical Devices Directive (98/79/EC) (IVDD) to the new regulation has started. The IVDR regulation will apply from the date of application, i.e. from May 26, 2022, with some provisions, including Notified Bodies and the Medical Device Coordination Group will enter into force sooner. Until the date of application of the IVDR, the laws and regulations adopted by the Member States under the IVDD will continue to apply. Under Art. 22 of the 1998 IVDD directive, the member states were obliged to prepare and introduce the national laws, regulations and administrative provisions necessary to comply with this directive by December 7, 1999 (IVDD) at the latest. The provisions of the directive were to apply with effect from 7 June 2000. As the provisions of the directive could be interpreted differently in different countries, it was possible for national provisions to differ. In the case of EU regulations, the provisions contained therein do not have to be transposed and adapted to national law. In May 2017, the European Parliament and the Council of the European Union published two new regulations on medical devices (2017/745/EU) (MDR) and in vitro diagnostic medical devices (2017/746/EU) (IVDR). Regulation 2017/746/EU (IVDR) replaces the existing Directive 98/79/EC on in vitro diagnostic medical devices (IVDD), which was adopted in 1998.
Directive 98/79/EC of the European Parliament and of the Council is the EU legal framework for in vitro diagnostic medical devices. This Regulation aims to ensure the smooth functioning of the internal market in the field of in vitro diagnostic medical devices, taking as its base a high level of health protection for patients and users and taking into account the small and medium-sized enterprises active in this sector. At the same time, this Regulation sets high standards of quality and safety for in vitro diagnostic medical devices in response to common safety concerns regarding such products. In the preamble to this Regulation, it is first and foremost noted that the scope of this Regulation should be clearly distinguished from other product legislation, such as medical devices, general laboratory products and products intended solely for research. In addition, it contains product safety and performance requirements designed to prevent accidents at work, including radiation protection. The provisions on Union market surveillance and control of products entering the Union market, laid down in Regulation (EC) No 765/2008, apply to this regulation. The preamble deals with guidelines aimed at ensuring the full effectiveness of in vitro diagnostic medical devices. These include: clear definition of the general obligations of individual economic operators, including importers and distributors, based on the new legal framework for placing products on the market, the provisions on in vitro diagnostic medical devices, both manufactured and used in within one public health institution. Such use should include measurement and delivery of results, public health institutions should be able to manufacture, modify and use devices in-house to meet, on a non-industrial scale, the specific needs of target patient groups that cannot be met with an appropriate level of performance using equivalent products available on the market. Importantly, producers should be required to put in place measures to ensure sufficient financial security against their possible liability under Council Directive 85/374/EEC. Such measures should be proportionate to the risk class, type of device and size of the company. The risk management system should be carefully aligned with and reflected in the device performance evaluation process, taking into account the clinical risks to be analyzed in performance studies, performance evaluation and post-market performance observation. For manufacturers not resident or established in the Union, the authorized representative plays a key role in ensuring that the products they produce comply with the relevant requirements and in acting as the contact person residing or established in the Union. As a general rule, devices should bear the CE marking to show their compliance with this Regulation so that they can be moved freely within the Union and put into service for their intended purpose. A key issue in fulfilling the objectives of this Regulation is the creation of a European database on medical devices (hereinafter the “Eudamed database”), which should integrate different electronic systems in order to collect and process information on devices available on the market and the relevant economic operators, certain aspects of assessment compliance, notified bodies, certificates, performance tests as well as market observation and surveillance. The regulation also specifies four types of device classes and the appropriate steps to be taken for the proper functioning of medical devices.
Below are the basic diagnostic conditions contained in the preamble:
1) EU reference laboratories should be able to verify – by means of laboratory tests – the performance declared by the manufacturer and the compliance of the devices presenting the highest risk.
(2) To ensure a high level of safety and performance, the demonstration of compliance with the general safety and performance requirements laid down in the Regulation should be based on clinical evidence.
3) The provisions for performance studies should follow well-established international guidelines in this field, such as the international standard ISO 14155:2011 on good clinical practice.
4) An electronic system at the European Union level should be established to ensure that all interventional clinical performance studies and other performance studies presenting a risk to participants are recorded and reported in a public database.
(5) Sponsors should report to Member States where intervention clinical performance studies and other performance studies involving a risk to subjects are conducted, specific adverse events and device defects occurring during such studies.
(6) A committee of experts, the MDCG, should be set up, composed of persons appointed by the Member States on the basis of their functions and expertise in the field of medical devices, including in vitro diagnostic medical devices.
As for placing the product on the market and putting into service, the Regulation sets forth the rule that a product may only be placed on the market or put into service if it is properly supplied and properly installed, maintained and used, and must also meet the general safety requirements that apply to it. Products manufactured and used in public health institutions, with the exception of devices for performance tests, are considered put into service.
As for distance selling, according to the Regulation, a product offered through an information society service must comply with the Regulation to a natural or legal person established in the Union. A copy of the EU declaration of conformity for that product shall be made available by the natural or legal person offering a product upon request from the competent authority. At the same time, it is forbidden to use any texts, names, trademarks, pictures and symbols or other signs that may mislead the user or patient as to the intended use, safety and operation of the device on labels, in the instructions for use, when making available, putting into use and in advertising of products.
When focusing on the general obligations of manufacturers, the Regulation determines that manufacturers establish, document, implement and maintain a risk management system. Manufacturers prepare and update the technical documentation of these products on an ongoing basis. Manufacturers shall keep at the disposal of the competent authorities the technical documentation, the EU declaration of conformity and, where appropriate, a copy of the relevant certificate, including any amendments and additions. Manufacturers have a system for recording and reporting incidents and field safety corrective actions. Manufacturers shall, on request from a competent authority, provide that authority with all the information necessary to demonstrate the conformity of the product, in an official Union language determined by the Member State concerned, and with all the documentation necessary for that purpose.
Detailed rules for the replacement of the authorized representative shall be clearly laid down in an agreement between the manufacturer, the former authorized representative. The agreement shall take into account: the date of expiry of the authorization of the existing authorized representative and the date on which the new authorized representative is authorized, the date by which the current authorized representative may be included in the information provided by the manufacturer, including any promotional material.
In order to place the product on the market, importers check that the product has been affixed with the CE marking, the manufacturer is known. Importers shall provide their full name, registered trade name or registered trade mark, registered place of business and an address at which they can be contacted on the product or on its packaging, or in a document accompanying the product, so that their location can be identified. Importers check that the product is registered in the electronic system. Importers shall keep a register of complaints, non-conforming products, product recall, and provide the manufacturer, authorized representative and distributors with any information requested to enable them to investigate complaints. Importers shall cooperate with the competent authorities upon request on any action they take to remove or, failing that, reduce the risks posed by articles they place on the market.
Distributors shall ensure that, while they are responsible for the product, the storage or transport conditions are in accordance with those specified by the manufacturer. Distributors who believe or have reason to believe that a product which they have made available on the market does not comply with the Regulation shall immediately inform the manufacturer and, where applicable, his authorized representative and the importer. Distributors who have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to the device they have made available shall immediately transmit this information to the manufacturer and, where applicable, to his authorized representative and the importer. Distributors shall, on request from the competent authority, provide it with all the information at their disposal which is necessary to demonstrate the conformity of the device, and shall make available to it all the documentation necessary for that purpose.
Manufacturers shall have at least one person within their organization responsible for regulatory compliance with the required expertise in the field of in vitro diagnostic medical devices. The person responsible for regulatory compliance does not suffer any negative consequences within the manufacturer’s organization in relation to the proper fulfilment of his obligations, regardless of whether he is an employee of the organization or not. The required expertise must be demonstrated by one of the following qualifications diploma, certificate or other evidence of formal qualifications four years of professional experience in regulatory matters or quality management systems in the field of in vitro diagnostic medical devices.
The EU declaration of conformity shall state that the requirements set out in the regulation have been met. The declaration contains all the information required to identify the Union legislation to which it relates.
The CE marking shall be affixed to the device or its sterile packaging in such a way that it is visible, legible and indelible. Where the affixing of such a marking is impossible or unjustified due to the nature of the product, the CE marking shall be affixed to the packaging. The CE marking shall also be placed on the instructions for use and on the sales packaging. The CE marking shall be affixed before the product is placed on the market. A pictogram or any other mark indicating a special risk or use may be placed under the CE marking.
Distributors and importers work with manufacturers or authorized representatives to achieve an appropriate level of product traceability. Economic operators must be able to identify to the competent authority: any economic operator to whom they have supplied a device directly, any economic operator who has directly supplied them with a device, any public health institution or health professional to whom they have supplied the device directly.
The system of unique device identification codes (hereinafter referred to as “UDI system”) enables the identification and facilitates the traceability of devices other than devices for performance testing. Includes: UDI generation, UDI placement on device label or packaging, UDI storage by economic operators, public health institutions and healthcare professionals, establishment of an electronic system of unique device identification codes. UDI code carriers are placed on the device label and on all higher levels of the packaging. Containers are not considered to be higher levels of packaging. The UDI code is used to report serious incidents. Economic operators shall retain and store – preferably in electronic form – the UDI codes of the devices.
Before placing the product on the market, its manufacturer assigns the product the Basic UDI-DI code. Before placing a device on the market, the manufacturer enters information about the product into the Eudamed database and verifies it in the Eudamed database, and then updates this information.
The Commission, after consulting the MDCG, shall set up and manage the electronic system to generate the unique registration number once for the purpose of collecting and processing the information that is necessary and proportionate to identify the manufacturer, as well as the authorized representative and the importer, where applicable.
Before placing a product on the market, manufacturers, authorized representatives and importers submit registration data to the electronic system for registration. After verifying the entered data, the authority obtains a unique registration number from the electronic system and issues it to the manufacturer, authorized representative or importer. The manufacturer uses a unique registration number when submitting an application for conformity assessment to a notified body.
The regulation provides for the preparation of product safety and performance summery. The safety and performance summary shall be made in writing in a manner that can be understood by the intended user and, where applicable, the patient; it is also publicly available through the Eudamed database. The safety and performance summary includes: device and manufacturer identification, intended use of the device and all indications, contraindications and target populations, device description, measurement traceability of assigned values, suggested profile and user training, information on any residual risks and any adverse effects, warnings and precautions.
The Commission, in consultation with the MDCG, creates, maintains and manages a European database on medical devices (Eudamed database). It includes the following electronic systems: electronic device registration system, UDI database, electronic economic operator registration system, electronic system for notified bodies and certificates, electronic system for performance studies, electronic system for observation and post-market surveillance, electronic system for market surveillance.