Medical devices (MDR, IVDR)
As of May 26, 2021, the Medical Devices Regulation (MDR), EU No 2017/745, and as of May 26, 2022, the In Vitro Diagnostic Medical Devices Regulation (IVDR), EU No 2017/746 are imposed. The regulations replace some of the old EU directives concerning medical devices.
To conduct a clinical investigation or a performance study of medical devices in Sweden, an approval from the Swedish Medical Products Agency or the Swedish Ethical Review Authority is needed depending on what type of authorization procedure that will be practiced. In cases where human biological samples, regulated by the Biobanks Act (2023:38), are included in the study, a biobank application with approval by the biobank custodian is required.
With these regulations, assessments of applications and notification for clinical investigations and performance studies of medical devices are jointly coordinated by the Swedish Medical Products Agency, the Swedish Ethical Review Authority and the Regional Biobank Centres (RBCs).
The RBC submits an opinion to the Swedish Ethical Review Authority that includes considerations regarding the subject information and the informed consent form, and to the Swedish Medical Products Agency concerning other issues.
At present, the RBCs has assignments from all regional biobanks, which means that a RBC will assess documentation relating to biological samples and give an opinion for all applications/notifications where newly taken samples are established in a regional biobank and where existing samples are released from, remain in or is to be established in a regional biobank. The opinion from the RBC is included when the request for information is sent to the sponsor. The assessment results in a national decision.
Due to the new process, all assessments, statements, complements of information, approval, and the establishing of biobank agreements are carried out faster than before.
For more information
When biobank samples are included
Biobank application
A biobank application is required for studies where newly collected samples will be established in and/or existing samples will be released from, remain in or be established in a regional biobank. The biobank application is then submitted to the RBCs on the same day as the application/notification for clinical investigation or performance study is submitted to the Swedish Medical Products Agency.
An RBC reviews the biobank application in parallel with the application/notification for clinical investigation or performance study and the sponsor is given the opportunity to address any considerations to the biobank application during the ongoing authorisation process, which means that the approval of the biobank application is accelerated after a decision on approval for a clinical investigation or performance study.
Read more about the application process for access to samples below under the heading – ”Process for biobank application in clinical trials or performance studies of medical devices”.
Newly collected biobank samples
Please note that tissue samples taken at the same time as healthcare samples are usually defined as ”existing healthcare care samples” even if they are newly taken in connection to the study.
In cases where newly collected biobank samples are included in the clinical investigation or performance study of a medical device, it needs to be clear who is to be the responsible biobank principal.
If the sponsor does not have its own biobank in Sweden and wishes to use the region’s biobank, it is recommended that the sample collection is established in one responsible biobank, even if the collection of sample takes place in several different regions. The sponsor is responsible for contacting a biobank in one of the participating regions early in the process, with a request if the biobank can be responsible for the sample collection.
If the sponsor has a registered biobank in Sweden, or if samples are to be established in another non-regional biobank, regions where biobank samples are newly collected must be notified that they should not be responsible for these biobank samples and that the samples will be established in another principal’s biobank. This is notified by completing the form T7a, signed by the concerned biobank’s biobank custodian and sent to the biobank coordinator in each concerned region in good time before the collection of samples will start.
Existing biobank samples
If the biobank application includes existing pathology/cytology samples, the local pathology laboratory should be contacted regarding the conditions in the current study and if they have any objections. Contact information can be found on Biobank Sweden’s service map under the heading ”Studiekoordinatorer patologi”. It is often an advantage that the local investigator contacts the pathology department in their region as they are familiar with the local conditions in the study.
In parallel with the application/notification for a clinical investigation/performance study, a pathologist will perform a national feasibility assessment. The sponsor is given the opportunity to address any objections from the pathologist during the ongoing permit process, which means that the biobank application can be approved more quickly after a decision on permission for a clinical trial/performance study.
The feasibility assessment assesses whether:
- the required amount of material is reasonable in relation to the analyses to be carried out
- the choice of material is suitable for the analyses to be carried out
- the total amount of material does not exceed the national assessment criteria developed in collaboration with the Svensk Förening för Patologi (SvFP): From biopsies (small materials) that are archived in a healthcare sample collection, a maximum of 40μm in total is considered reasonable to distribute across all analyses, provided that the material is sufficient. From surgical material (larger material) that is archived in a healthcare sample collection, a maximum of 3–5 sections (4μm) per assay (maximum 2 sections per IHC marker/assay (one back-up section per marker)) and 30μm for DNA extraction are considered reasonable.
Please note that the amount of material in the criteria cannot be guaranteed in any way. In the case of biopsies, this amount is rarely even left in an existing block after sections have been used for care and diagnostics.
Whether the material is possible to access in the relevant regions is always assessed by the biobank concerned. The biobank application is approved by the biobank custodian after permission for a clinical investigation or performance study and after approval by the relevant sample collection controller. Requested material can only be provided on the condition that sufficient material regarding type and quantity is left in the healthcare sample collection for the patient’s possible future care, diagnosis and treatment.
For more information, see assessment form TY4.
The process of the biobank application in clinical investigations or performance studies of medical devices
Prior to submitting the biobank application
- Contact the RBCs early in the process, preferably at the planning stage, for guidance regarding the biobank application by e-mailing kliniskaprovningar@biobanksverige.se.
- A) Responsible biobank belongs to a region – Complete forms T1.1. If the application includes existing samples, form L1a and/or L1b is also to be completed.
- B) Responsible biobank does not belong to a region – Newly collected samples could be established directly in the responsible biobank by the biobank custodian and according to the biobank’s own routines. No biobank application should be sent to RBC. If existing samples should be released from a region’s biobank, form L1a and/or L1b should be completed. All forms can be found on Biobank Sweden’s document page under the toggle menu called “Research – Documents in English”.
- Send the un-signed biobank application to kliniskaprovningar@biobanksverige.se at the same time as the application/notification for clinical investigation/performance study of medical devices is submitted to the Swedish Medical Products Agency.
Assessment
- RBC validates and assesses the biobank application. If the application includes existing pathology/cytology samples, a feasibility assessment will be made by a pathologist.
Please note: RBC will communicate regarding the biobank application directly to the sponsor (or the person who represents the sponsor by submitting the biobank application). All communication regarding the clinical investigation must go through the Swedish Medical Products Agency or the Swedish Ethical Review Authority.
Statement
- RBC will present the statement in form TY5 (RBC’s assessment report) and send to the sponsor by e-mail together with last date for response.
- If existing samples are to be released, RBC prepares the form for release of samples (T1.2) and sends it to the sponsor for possible correction together with the statement.
- Sponsor states the response to considerations in the form TY5 and send it back to RBC.
Final assessment
- RBC sends out final biobank application forms together with TY5 containing final assessment and instructions for approval of the biobank application.
Approval
Please note that the biobank application is approved by the biobank custodian after permission for a clinical investigation or performance study and after any endorsement by the relevant sample collection controller (if existing samples are included). If the deciding biobank region applies ”wet ink” signing, the sponsor must submit all signed biobank applications to the deciding biobank(s) according to the instructions in TY5. for decision by an authorized representative of the biobank. Many biobanks instead apply digital signing, which is stated in TY5.
The following applies for assessed biobank applications
- Remaining documentation does not need to be enclosed but are sent to the appropriate biobank by the RBC.
- If any modifications are made to the biobank application after the assessment, this must be stated in a separate covering letter addressed to the representative that is going to make the final decision – this may prolong the process.
- Please note: the biobank agreement does not come into force until the biobank application and all appendices, if any, are signed by sponsor and approved and signed by an authorised representative of the biobank.
Applications outside the scope of the IVDR
This process does not apply to performance studies of a medical device for in vitro diagnostics, that do not fall within the scope of the IVDR, and where the research principal has submitted an application directly to the Ethical Review Authority in their application system Ethix. The Medical Products Agency provides guidance on this:
Handling of applications and notifications | Swedish Medical Products Agency (lakemedelsverket.se)
For these applications, the biobank application should instead be sent directly to the biobank in question according to the following description:
Document K2.1 (form selector)
Request of alterations of the biobank agreement
If a request for substantial modifications of a clinical investigation or performance study is made and the modification concerns a previously approved biobank agreement (e.g., modifications in study design that affect the agreement, change of sponsor, change of investigators, added sites, more samples or new sample types*), a request for alteration needs to be submitted to the RBC by e-mailing kliniskaprovningar@biobanksverige.se.
If it concerns a biobank agreement established for clinical investigation or performance study according to legislation before MDR and IVDR (established on form L1 or N1a), a copy of the earlier approved and signed agreement shall be appended to the request for alteration to facilitate and speed up the assessment.
Forms for alterations to previously approved biobank applications for clinical investigations and performance studies
- For ongoing biobank agreements established under the previous multicentre principle (on forms N1a, T1/T1a/T1c), form N2 shall be used for request of alterations.
- For all other ongoing agreements, form T1.3 shall be used for request of alterations.
All forms are available on the page with all documents.
*Please note, there can be other substantial modifications that concern the approved biobank application.
There can also be modifications that are non-substantial modifications for the clinical trial but that still need to be reported to the RBC, e.g., more research patients in Sweden and an extended sample collection period in Sweden.
For questions, please contact
A lot of frequently asked questions can be found on our FAQ-page.
For additional questions, you are welcome to contact us by e-mailing:
kliniskaprovningar@biobanksverige.se