Specific rules for medical devices
Medical devices are in the EU regulated by two categories that follow different regulations:
- For medical devices, the EU Regulation on Medical Devices (MDR) applies. New rules apply within the EU from 26 May 2021, additional rules apply in Sweden from 15 July 2021.
- For in vitro diagnostic medical devices, the EU Regulation 2017/746 on in vitro diagnostic medical devices (IVDR) applies. New rules apply within the EU from 26 May 2022.
Medical devices, EU regulation MDR
Find out whether your idea includes a medical device
If you are planning for a medical technical clinical trial on as part of the product development prior to CE marking, you probably already know whether the product in your study is defined as a medical technology product or not. However, this is not always as obvious in studies initiated by academia or by healthcare.
Medical devices include a large number of different products which in summary can be described as different technical solutions intended for use on humans for a medical purpose. You can read about the complete definition of a medical device in the EU regulation on medical devices, on the Swedish Medical Products Agencys´s website there is also information about definitions.
The so-called intended purpose is the manufacturer’s description of a product’s area of use and determines whether it shall be defined as amedical device. If you intend to study a product that you have designed yourself, if you want to use a product for medical purposes that was not originally intended for it, or if you have modified an existing medical device, it may be that you or the organisation you belong to are the manufacturer. In these cases it is you yourselves who are responsible for finding out whether the medical product fulfills the definition for a medical device and thus must also follow the special rules that apply to clinical trials on medical devices.
If you are proposing to use a commercially available product in your study, you can find out whether it is defined as a medical device by contacting the manufacturer.
Sometimes it is difficult to assess whether the product you are proposing to use is a medical device or not. If so, please contact the Swedish Medical Products Agency for advice. The EU Commission also publishes guidelines dealing with delimitation problems around, for example, medical technology software.
Is the product ready for use in a clinical investigation of medical devices?
Before the medical device can be used in a clinical investigation of medical devices , it shall fulfil the regulatory, so-called general, requirements for safety and performance, as far as is possible without testing it on humans. For example, technical and biological safety tests shall have been conducted and all risks shall have been minimised and balanced against expected clinical benefit. Read more about the regulations’ general requirements below on this page.
Clinical evaluation of the product
A manufacturer planning to perform clinical investigation of medical devices prior to CE marking of their product must first perform a clinical evaluation.
A method description of how to carry out clinical evaluation is available in the EU regulation on medical devices, appendix XIV. In brief, the method consists of collecting data from literature according to specific criteria, and then evaluating them in a systematic way. The evaluation is summarised in a written report, stating whether the device can be shown to fulfil all the general requirements on safety and performance using existing data, or whether there are aspects that may need to be tested in new medical technical clinical studies.
Formulate the hypothesis or research question
For the medical device to be used to its best potential in health and medical care, the manufacturer should ensure that the characteristics intended to build up evidence for are also those that the end user is interested in. Claims about the safety and performance of a device must be proved using clinical data, and it can therefore be valuable to discuss questions with key opinion leaders, proposed users, diagnosis groups or representatives of the clinical profession.
The risk management process used during the development of a medical device, together with the results from the clinical evaluation, provide information on the aspects of the products that should be evaluated, and thereby which questions should be answered in a possible clinical investigation of medical devices.
The development stage of the product is also of importance to how the hypothesis should be formulated, and whether the study should have an exploratory or confirmatory design, or perhaps both. You can read more about study design and statistical considerations on the pages Planning and Analysis on this website.
Most clinical investigations of medical devices require permission from the Swedish Medical Products Agency
Most clinical investigations of medical devices shall be notified to the Swedish Medical Products Agency and some also needs a permit from the same authority. Read more about notifications and permits from the Swedish Medical Products Agency on the page Planning or on the Swedish Medical Product Agency´s website.
Recommendation to follow good clinical practice
The Swedish Medical Products Agency recommends that all medical technical clinical trials are conducted according to the European standard ISO 14155:2020, Clinical investigation of medical devices for human subjects – Good clinical practice. The purpose of ISO 14155:2020 is to:
- protect the rights, safety and well-being of study participants
- safeguard scientific implementation and reliable study results
- define responsibilities
- function as an aid for the parties involved in the assessment whether medical devices correspond to the general requirements on safety and performance
All Swedish healthcare personnel have access to many standards, including ISO 14155:2020 via internet by means of an agreement between Swedish Standards Institute (SIS) publishers and SKR.
General requirements and harmonised standards
The requirements set for safety and performance for medical devices are known as the “general requirements” and are listed in Appendix I to EU regulation on medical devices.
To show that the product fulfils the requirements, you can choose to follow the internationally standards that have been developed in various areas. Harmonised standards have been developed to comply with the requirements in the regulations. Working according to standards is voluntary, but they can be a good help to show that conformity with a specific requirement in the regulation. Work is underway to harmonize standards with the EU regulation on medical devices. For the time being, you can use the standards that have been harmonized with the previous directives and that have been published on the EU Commission’s website.
Depending on the product studied, different standards may be applicable, and different investigations of the product may need to be done before the general requirements on safety and performance can be said to be met as far as possible without testing the product on humans. Only then is it ready for use in a medical technical clinical trial.
If you need help in the choice of suitable standards to use, you can find references to relevant resources you can use via the industry organisation Swedish Medtech, or MEDEA, for example. Swedish Life Sciences Database has compiled a searchable summary of the various actors within the medical devices area covering both medical device consultants, and also other companies with a medical device profile.
Medical devices for in vitro diagnostics, EU regulation IVDR
If your idea includes in vitro diagnostic products
In vitro diagnostic (IVD) products include products that are intended to be used for the examination of samples from the human body in order to obtain information about, for example, treatment effects or disease states.
You can read the complete definition of an in vitro diagnostic product in the EU regulation on in vitro diagnostic medical devices.
Sometimes it is difficult to assess whether the product you intend to use is a medical device for in vitro diagnostics or not. In that case, contact the Swedish Medical Products Agency for advice.
Clinical performance studies
As a general rule, clinical performance studies should always be performed to prove the clinical performance of a product, unless it is justified to rely on other sources of clinical performance data.
When conducting clinical performance studies, the data obtained should be used in the performance evaluation and form part of the clinical evidence for the product.
A manufacturer planning to perform clinical performance studies prior to CE marking of its product must first perform a performance evaluation. The performance evaluation of a product is a process where data is assessed and analyzed to prove the scientific validity, the analytical performance and the clinical performance for the intended purpose of the product.
A methodological description of how to conduct clinical evaluation can be found in the EU Regulation on in vitro diagnostic medical devices, Article 56 and Part A of Annex XIII. In short, the method is based on clinical data from the literature being collected according to specified criteria and evaluated in a systematic way. The evaluation is summarized in a written report stating whether the product can be shown to meet the general requirements for safety and performance (see more about the general requirements further down the page) using existing data or if there are aspects that need to be tested through new clinical performance studies.
Formulate a hypothesis or research question
In order for the in vitro diagnostic product to be of the best use in healthcare, the manufacturer should ensure that the properties on which it intends to build evidence are also those that the final recipient is interested in. Claims about the safety and performance of a product must be demonstrated through clinical data, and it may therefore be valuable to discuss issues with leading clinical researchers in the field, potential users, diagnostic groups or representatives of the clinical profession.
The risk management process applied during the development of an in vitro diagnostic product together with the results of the performance evaluation provides information on which aspects of the product should be evaluated and thus which questions should be answered in a clinical performance study.
Read more about study design and statistical considerations under the pages planning and analysis.
Some performance studies require review by the Swedish Medical Products Agency
With the application of the EU regulation on medical devices for in vitro diagnostics, notification or application for a permit from the Swedish Medical Products Agency is required for certain clinical performance studies on IVD products.
Recommendation to follow good study practice
Clinical performance studies should be conducted in accordance with Good study practice (GSP), as described in the international standard ISO 20916: 2019 In vitro diagnostic medical devices - Clinical performance studies using specimens from human subjects - Good study practice.
The purpose of ISO 20196: 2019 is to:
- protect the rights, safety, dignity and well-being of the subjects
- ensure scientific implementation and reliable study results
- define responsibilities
- serve as an aid to the parties involved in the assessment that in vitro diagnostic products comply with the general safety and performance requirements.
General requirements and harmonized standards
The safety and performance requirements for in vitro diagnostic products are called the general requirements and are listed in Annex I to the EU Regulation on in vitro diagnostic medical devices.
To show that the product meets the requirements, you can choose to follow international standards that have been developed in different areas. Harmonized standards have been developed to meet the requirements of the regulations. It is voluntary to work according to standards, but they can be a good help to show compliance with a specific requirement in the regulations. Work is underway to harmonize standards with the EU regulation. For the time being, you can use the standards harmonized with the previous directives and published on the European Commission's website. There are also EU-wide specifications that should be followed.
Depending on the product being studied, different standards will be applicable and different studies of the product will need to be done before the general requirements for safety and performance can be said to be met.