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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


Recommendation to follow good clinical practice

The clinical study must not start until it has been approved by the approval bodies in question. Read more about notification and application on the page Application on this website. During implementation of the study, the clinical investigation plan (CIP) approved by the authorities must be followed.

The Swedish Medical Products Agency recommends that clinical investigations of medical devices are conducted according to ISO 14155:2020 - Clinical investigation of medical devices for human subjects – Good clinical practice. The standard includes guidance on role allocation and responsibilities in a clinical investigation of medical devices, you can read more on this in the Planning section. This standard, among others, is available free of charge to employees of the Swedish Association of Local Authorities and Regions (SALAR), including Swedish healthcare personnel, via an agreement between Swedish Standards Institute (SIS) and SALAR and can be accessable through SIS website.

Access to standards, SIS website (login required) External link.

Medical device perspectives on consent from study participants
Ahead of all clinical studies and unless an exception has been approved, study participants shall provide informed consent according to the Ethical Review Authority’s guidance for study participant information and consent. When it comes to clinical investigatons of medical devices there are further requirements for the patient information and consent procedure; these are specified in the EU regulation on medical devices and ISO 14155:2020.

In addition, supplementary Swedish legislation must be followed with regard to the consent procedure in medical clinical trials involving minors and persons who are not competent to make decisions. In the case of a medical technical clinical trial involving children, both guardians must give their informed consent in the child's place. Minors who have reached the age of 15, and who understand what it means to participate in the trial, must also give their informed consent themselves.

The Ethics Review Authority's guide to study participant information and consent (in Swedish) External link.

Requirements for patient information and the consent procedure, EU regulation on medical devices External link.

Requirements for consent procedure in medical clinical trials on minors and persons who are not competent to make decisions, Act with supplementary provisions to the EU regulation on medical devices (in Swedish) External link.

Requirements for patient information and the consent procedure in ISO 14155: 2020, SIS website (login required) External link.

Summarise documentation in study folders
ISO 14155:2020 contains information on the study documentation that needs to be drawn up in aclinical investigation of medical devices involving medical devices. A summary of the documentation shall be held both by the investigator (site file) and by the sponsor (sponsor file). The summaries shall include all the documents required to make it possible to evaluate the implementation and quality of the study. After conclusion of the study, it shall be possible to reconstruct the study based on the documentation in the study files. The site file shall include all the documentation that is important for the own clinic, and the sponsor file shall include the overall documentation for all participating clinics. Information that can identify study participants must not be included in the sponsor file.

Initiation visit
Ahead of the study start, the sponsor and/or monitor shall carry out an initiation visit to all participating clinics, or hold a joint meeting for all principal investigators and personnel. The purpose is to go through the study protocol and all study-related activities with the principal investigators and other personnel taking part in the work on the study, and to ensure the clinic has all the necessary equipment, resources and documentation, including approvals, to enable them to begin the study. The sponsor shall document a summary of the meeting content and a list of participants, with names, initials, signatures and functions. The monitor shall write a report of the meeting.

Handling of medical devices in clinical investigation
It shall be possible to track medical devices and any comparison devices in a clinical investigation of medical devices requiring a permit from their dispatch to the trial site until they are returned or destroyed when the study ends.

That means, for example, that such as the unique identification of each product, expiry date, date the investigator received the product and date of return shall be documented.

Medical devices that are evaluated in a clinical investigation shall be marked with the expression “for clinical investigation of medcial products only”.

The sponsor has overall responsibility for the medical device, and for educating clinic personnel in how to use the product and the documentation required for traceability. The principal investigator shall ensure that the medical device is only used by authorised users and in accordance with the clinical investigation plan (CIP) and other study instructions.

Safety reporting of device deficiencies and adverse events
In clinical investigations of medical devices with products that are not yet CE-marked or with products that are not used as intended, special safety reporting must be done during the course of the study. This also applies to tests on already CE-marked products that are used for the intended purpose if serious deviating events occur that are related to study-specific procedures.

The reporting of adverse events and product defects is important both for the people participating in the study and for future patients. Processes for reporting must be developed before the study starts.

The sponsor is responsible for ensuring that all serious adverse events that are related to the use of the medical device, a comparison product or the study procedure are reported immediately to the Swedish Medical Products Agency during the course of the study. This also applies to product defects (device deficiency) which could have led to serious deviating events if appropriate measures had not been taken or if the conditions had been less favorable. The safety reporting is summarized at the end of the study and is included as part of the study's final report.

More information on writing a final report, see the Publication section on this website

The sponsor has overall responsibility for safety reporting but the investigator is responsible for registering and assessing all adverse events and device deficiencies at the trial site on an ongoing basis. The investigator shall make an assessment of the degree of seriousness and links between the use of the medical device and the adverse event and reports this to the sponsor.

Further information onsafety reporting and and reporting of adverse events and device deficiencies is to be found in the EU regulation on medical devices, MDCG 2020-10/1 and in ISO 14155:2020.

Guidance on safety reporting in clinical investigations (MDGC 2020-10/1) External link.

For studies on CE-marked products used in the context of the intended purpose of the product, the regular routines of healthcare apply for reporting negative events and incidents. An exception applies, however, to serious deviating events that are related to study-specific procedures that must also be reported to the Swedish Medical Products Agency in these studies.

Reporting of adverse events and incidents, the Swedish Medical Products Agency's website External link.

Medical device perspectives on data collection
The case report form (CRF) created in paper or electronic format during the planning of the study needs to be completed in good time before the study start, see also the page Planning on this website. The persons involved in data collection shall have been trained in how the case report form shall be used, and within what timeframes data must be registered. The principal investigator at a clinic shall confirm that the data collected are correct, complete, legible and registered within a reasonable time interval. The investigator shall also make data available to monitors, auditors and public authorities at inspections.

Data generated during the study can be registered direct in the case report form, and then constitutes source data. Source data can also be generated via, for example, ECG printouts or laboratory analysis reports, or be registered for the first time in patient notes or working papers, and then be transferred to the case report form. It is important to identify source data before the study start, to ensure data are handled uniformly, and that all original data are saved.

Checks of source data are an important part of the quality control carried out by the monitor during a study, and are also carried out at any inspection.

All study data including source data must also be stored in a secure way in order to function as a reliable reference for future use.

Information on the requirements for data collection in clinical studies involving medical devices, including specific requirements for electronic case report forms is available in ISO 14155:2020.

Implementing monitoring
The monitoring is carried out as a quality control of participating trial sites. The monitor shall check that the personnel involved in the study have the correct qualifications and prerequisites, that the clinical investigation plan (CIP) and applicable laws and regulations are followed, that that data is correctly registered in the study participants’ case report forms (CRF). All monitoring activities shall be documented in a written report to the sponsor.

Monitoring is a requirement for clinical investigations of medical devices and should be carried out before, during and after the study. The sponsor shall draw up a monitoring plan for the study before it starts. The scope and frequency of the monitoring shall be based on an evaluation of the study’s risks, design and complexity and are described in the monitoring plan. More detailed information on monitoring can be found in ISO 14155: 2020.

The monitoring shall be carried out by a person, the monitor, who is independent of the investigator and appointed by the sponsor. A monitor may not be involved in the practical implementation of the study.

More about the monitor's qualifications on the page Planning on this website.

Audit and inspection
The audit involves the sponsor or a third party appointed by the sponsor conducting a scrutiny to evaluate compliance with the study protocol and applicable laws and regulations for study execution, data handling and reporting. An audit may be conducted at all parties involved in a study, and is independent and separate from the routine monitoring. The reasons why an audit is conducted vary, and may be part of the sponsor’s quality program, constitute a check of the effectiveness of the monitoring, be done in conjunction with a suspicion of misconduct, or as a preparation ahead of inspection.

More information on audits in ISO 14155: 2020, SIS website External link.

An inspection is a scrutiny carried out by the supervisory authority for the clinical investigations of medical devices requiring a permit, and constitutes an official scrutiny and review of the study documentation, equipment, resources, registrations and quality measures at the clinics and other parties involved in the study.

The principal investigator is obliged to make study documentation available at the request of a monitor, auditor or inspection authority.

Change to an approved application, or interruption of an ongoing study
If you need to make a significant change to a medical technical clinical trial an application for change shall be submitted to the Swedish Medical Products Agency which which coordinates the review of the change with the Swedish Ethical Review Authority.

No separate change application needs to be sent to the Swedish Ethical Review Authority, but a special form for ethical review of the change must be sent to the Swedish Medical Products Agency. Application for change to the Swedish Medical Products Agency is made via the same electronic process that was used in the original application.

The application for change, the Swedish Medical Products Agency's website External link.

Special form for ethical review of the change application, the Swedish Ethical Review Agency (in Swedish) External link.

If, for any reason, the study needs to be interrupted, or an individual clinic closes down prematurely, this shall also be reported to the Swedish Medical Products Agency. The reason for the study interruption shall be documented, and may for example be a suspicion of an unacceptable risk for study participants, or a clinic that diverges seriously or repeatedly from the study processes. If the study is temporarily interrupted or terminated prematurely due to safety reasons, the Swedish Medical Products Agency must be notified within 24 hours. If the interruption / termination is made for other reasons, this must be reported within 15 days. ISO 14155:2020 has additional description ofthe activities that should be carried out in the event of an interruption or premature closure of a study.

Concluding a study and preparing for report writing
When a participating clinic has completed the final study activities, and registered and signed off all data in the case report form, the monitor shall carry out a closure visit. The monitor shall ensure that all data reporting and documentation are correct and complete, that all questions have been answered and that any remaining material is destroyed or returned.

The study sponsor is responsible for ensuring all closure activities have been completed, shall check that all study data are complete and correct, and carries out the final follow-up if there any uncertainties remain. Thereafter, the study database is considered final and complete, the database can be closed and the statistical analysis starts.

Guidance on closure activities for participating clinics is available in ISO 14155:2020.

Medical devices for in vitro diagnostics, EU regulation IVDR


Recommendation to follow good clinical practice
A clinical performance study may not start before a permit from the relevant authorities is in place. Read more about registration and application under the section Application. The implementation of the study must follow the clinical performance study plan approved by the authorities.

The Swedish Medical Products Agency recommends that clinical performance studies of in-vitro diagnostic products be performed in accordance with ISO 20916: 2019 'good study practice'. The standard contains guidance on the division of roles and responsibilities in a medical technical clinical trial. The main text of the standard and the appendix on handling deviant events must be used for all performance studies, while other appendices such as performance study plan, trial handbook, recommended study documentation are not mandatory for performance studies that only require notification to the Medical Products Agency.

Through an agreement between the Swedish Standards Institute (SIS) and Sweden's Municipalities and Regions (SKR), all Swedish healthcare staff have free access to many standards on the SIS website.

Free access to standards, SIS website External link.

Medical technical perspectives on consent from the study participants
Prior to all clinical trials, study participants must, unless an exception is approved, provide informed consent in accordance with the Swedish Ethical Review Authority's guidelines for study participant information and consent. With regard to clinical performance studies, there are additional requirements for patient information and the consent procedure specified in the EU Regulation on medical devices for in vitro diagnostics and ISO 20916: 2019.

In addition, supplementary Swedish legislation must be followed with regard to the consent procedure in clinical performance studies involving minors and persons who are not competent to make decisions.

The Ethics Review Authority's guidance on study participant information and consent (in Swedish) External link.

Requirements for consent procedure in medical clinical trials on minors and persons who are not competent to make decisions, Act with supplementary provisions to the EU regulation on medical devices (in Swedish) External link.

Requirements for patient information and the consent procedure in ISO 20916: 2019, SIS website External link.

Compile the documentation in study folders
ISO 20916: 2019 contains information on which study documentation should be prepared in a clinical performance study. A compilation of the documentation should be available from both the testing site conducting the study and the sponsor. The summaries should contain all the documents required for it to be possible to evaluate the study's implementation and quality. When a study is completed, it must be possible to reconstruct it based on the documentation in the study binders. At the test site, all documentation that is important for the individual test site should be available and with the sponsor the overall documentation for all participating test sites. Information that can identify study participants must not be available from the sponsor.

Initiation visit
Prior to the start of the study, the sponsor and / or monitor should carry out initiation visits to all participating test sites or hold a joint meeting with all responsible testers and staff. The purpose is to review the clinical performance study plan and all study-related activities with responsible examiners and other staff who will participate in the work of the study, and to ensure that the examination center has all the necessary equipment, resources, training and documentation, including approval, to start. the study. It is recommended that the sponsor document an overview of the meeting content and a list of participants with names, initials, signature and function. The monitor should write a report from the meeting.

Management of in vitro diagnostic product in performance study
In vitro diagnostic products and any comparative products in a clinical performance study should be traceable from the time they are sent to the test site to their return or destruction when the study is completed.

This means, for example, that the product's unique identity, expiration date, date when the tester received the product and the date of return must be documented.

In vitro diagnostic products evaluated in a performance study should be labeled "for clinical trial only".

The sponsor has the overall responsibility for the product and for training staff in how the product is used and what documentation is required for traceability. The responsible examiner ensures that the in vitro diagnostic product is used only by authorized users and in accordance with the clinical performance study plan and other study instructions.

Safety report product defects and adverse events
In clinical performance studies, special safety reporting must be done during the course of the study in accordance with IVD legislation. This also applies to performance studies on already CE-marked products that are used for the intended purpose if serious deviating events occur that are related to study-specific procedures.

The reporting of adverse events and product defects is important both for the people participating in the study and for future patients. Processes for reporting must be developed before the study starts.

The sponsor is responsible for ensuring that all serious adverse events related to the use of the in vitro diagnostic product, a comparison product or the study procedure are reported immediately to the Swedish Medical Products Agency during the course of the study. This also applies to product defects (device deficiency) which could have led to serious deviating events if appropriate measures had not been taken or if the conditions had been less favorable. The safety reporting is summarized at the end of the study and is included as part of the study's final report.

More information on writing a final report can be found on the Publication

The sponsor has the overall responsibility for safety reporting, but the examiner is responsible for continuously registering and assessing all deviating events and product defects at the test site. The tester makes an assessment of the severity and connection between the use of the medical device and the anomalous event and reports this to the sponsor.

More information on safety reporting and established time frames for reporting can be found in the EU regulation on medical devices for in vitro diagnostics and ISO 20916: 2019.

In clinical performance studies on CE-marked products that are used within the framework of the product's intended purpose, the healthcare routines' regular routines for reporting adverse events and incidents apply. An exception applies, however, to serious deviating events that are related to study-specific procedures that must also be reported to the Swedish Medical Products Agency in these studies.

Reporting of adverse events and incidents, the Medical Products Agency's website External link.

Medical technical perspectives on data collection
The data collection form (CRF) created on paper or in electronic format during the planning of the study needs to be completed before the start of the study, see information on the planning page. The people involved in the data collection should have received training in how the data collection form should be used and within what time frames the data should be registered. The responsible examiner at a clinic certifies that the collected data is correct, complete, readable and registered within a reasonable time interval.

Information on data collection forms (CRF) on the Planning page

Data generated during the study can be registered directly in the data collection form and then constitute source data. Source data can also be generated via, for example, ECG transcripts, laboratory analysis reports or recorded for the first time in patient records or on worksheets, and then transferred to the data collection form. It is important to define source data before the start of the study, so as to ensure uniform data management and that all original data is preserved.

Control of source data is an important part of the quality review that the monitor does during a study and is also done during any inspection by authorities.

All study data, including source data, must be stored securely to serve as a reliable reference for the future.

Information on recommendations for data collection in clinical performance studies, including specific recommendations for electronic data collection forms, can be found in ISO 20916: 2019.

Perform monitoring
Monitoring is carried out as a quality control at the participating test site. The monitor checks that staff involved in the study have the right qualifications and prerequisites, that the clinical performance study plan and applicable laws and regulations are followed, and that data is correctly collected and registered. All monitoring activities are documented in a written report to the sponsor.

Monitoring is a requirement for clinical performance studies and should be done before, during and after the study. The sponsor must establish a monitoring plan before the start of the study. The scope and frequency of the monitoring is based on an evaluation of the study's risks, design and complexity and is described in the monitoring plan. More detailed information on monitoring can be found in ISO 20916: 2019.

The monitoring is performed by a person independent of the examiner who is appointed by the sponsor. A monitor must not be involved in the practical implementation of the study.

More about the monitor's qualifications on the Planning page

Audit and inspection
Audit means that the sponsor or a third party appointed by the sponsor conducts a review to evaluate compliance with the clinical performance study plan and applicable laws and regulations for study execution, data management and reporting. An audit can be performed on all parties involved in a study and is performed independently of the routine monitoring. The reason for conducting an audit varies and can take place as part of the sponsor's quality program, as a check on the effectiveness of the monitoring, in connection with suspected mismanagement, or as a preparation for inspection by an authority. More information about audits can be found in ISO 20916: 2019

Inspection is a review carried out by the supervisory authority for the clinical performance study and is an official review and review of study documentation, equipment, resources, registrations and quality measures at clinics and other parties involved in the study.

The responsible examiner has an obligation to make study documentation available at the request of a monitor, auditor or inspecting authority.

Changes in approved application or interruption in ongoing study
If you need to make a significant change in an ongoing clinical performance study, an application for a change must be submitted to the Swedish Medical Products Agency, which coordinates the review of the change with the Swedish Ethical Review Authority. Applications for changes to the Swedish Medical Products Agency are made via the same electronic process used in the original application.

Application for change, the Medical Products Agency's website External link.

Special form for ethical review of the change application (in Swedish) External link.

If the study for any reason needs to be interrupted or an individual trial site needs to be closed prematurely, this must also be reported to the Swedish Medical Products Agency. The reason for the study interruption must be documented and may, for example, be a suspicion of unacceptable risk for the study participants or that a test site deviates seriously or repeatedly from the study processes. If the study is temporarily interrupted or terminated prematurely due to safety reasons, the Swedish Medical Products Agency must be notified within 24 hours. If the interruption / termination is made for other reasons, this must be reported within 15 days. ISO 20916: 2019 contains a further description of the activities that should be performed in the event of interruption and premature closure of a study.

To complete a study and prepare for report writing
When a participating trial site has completed the last study activities and registered all data, the monitor makes a closing visit. The monitor ensures that all data reporting and documentation is correct and complete, that all possible questions have been answered and that leftover material or in vitro diagnostic products have been destroyed or returned.

The study sponsor is responsible for ensuring that all closing activities are carried out, checks that all study data is complete and correct, and makes the final follow-ups if any ambiguities remain. Thereafter, the study database can be considered final and complete, the database can be closed and the statistical analysis can begin.

Guidance on closing activities at participating testing sites can be found in ISO 20916: 2019.

Information on data management can be found on the Analysis page