Clinical trials on medicinal products for human use according to Clinical Trials Regulation (CTR)
As of January 31st, 2022, the EU regulation regarding Clinical trials of medicinal products for human use, EU No 536/2014, is imposed. In Sweden this also affects the process for biobank applications in clinical trials.
According to the EU regulation for CTR, an application for clinical trial is submitted through the web portal CTIS (Clinical Trial Information System). If a clinical trial is to be conducted in several EU countries a joint assessment is made by the involved countries. In Sweden, a joint assessment is made by the Swedish Medical Products Agency and the Swedish Ethical Review Authority, and in cases where the trial includes human biological material, and where the Biobank Act (2023:38) applies, an assessment is also made by an RBC.
The RBC gives their 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, all RBCs has assignments from all regional biobanks, which means that an RBC will assess documentation relating to biological samples and submit 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 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, made by the Swedish Medical Products Agency, available on CTIS.
For more information about how to apply according to the EU regulation, CTR, visit the Swedish Medical Products Agency’s webpage.
Application documents for clinical trials
If a clinical trial is to include human biological material, a document is to be submitted into CTIS with a description of the handling of the biological material. A useful document called “Följsamhet med regler för hantering av biologiska prov” has been created by Biobank Sweden, the Swedish Medical Products Agency and the Swedish Ethical Review Authority and can be seen as a Swedish equivalent of the English document ”Compliance with applicable rules for biological samples”. You can download the document at the webpage of the Swedish Medical Products Agency:
Följsamhet med regler för hantering av biologiska prov
Transitional rules and the transfer of active clinical trials
Transitional rules
As of January 31, 2023, it is no longer possible to apply for samples according to the old directive (2001/20/EC)/national legislation. If you already have an ethical approval – apply for access to samples with document L1.1 and/or L1.2.
For guidance, use our K2.1 form selector
Documents can be found here: Documents – biobanksverige.se
Transfer of trial to CTR “transitional trials” and subsequent update of biobank agreement
Information about transition of trial to CTR
Active clinical trials, approved according to the old directive (2001/20/EC)/national legislation, need to be transferred over into CTIS according to CTR (EU No 536/2014) before January 31, 2025, to be allowed to continue.
Please note that all information provided to subjects must be accurate as to the responsibilities of the clinical trial. The sponsor is responsible for assessing whether the documentation needs to be updated and if a substantial modification is needed.
Example of investigator-initiated clinical trials:
The same organisation represents the clinical trial towards authorizing authorities, i.e., the former research principal in previously ethical approval is the same organisation that applies as a sponsor in CTIS when transferring the trial to CTR. In this case, the existing biobank agreement does not need to be updated in connection with the transition.
Example of company-initiated clinical trials:
Before CTR was applied, a clinical trial of medicinal products could have a research principal (with a principal/national coordinating investigator) who applied for ethical approval from the Ethical Review Authority and also access to samples from the biobank/RBC. The sponsor applied for a permit for clinical trials from the Medical Products Agency. With CTR, the concept of research principal and principal/national coordinating investigator is not applicable, and sponsor is instead responsible for the entire trial. In these cases, the biobank agreement must be updated and the sponsor is stated as responsible instead of the principal/national coordinating investigator.
Update of biobank agreements after transition of trial to CTR:
The sponsor must send a request for updating the biobank agreement to: kliniskaprovningar@biobanksverige.se at the same time as the transfer of the trial to CTR has been approved. The request should contain the current EU trial number and all previously approved biobank agreements.
The responsible RBC then notifies current biobanks about the update of biobank agreements.
Material transfer agreements (MTAs) where signing parties have not changed, e.g. signed by the responsible biobank and sponsor, do not need to be updated.
Transitional provisions in the Biobank Act 2023:38 for clinical trials
Please note that the repealed Biobank Act still applies to certain clinical trials until January 31, 2025. The following trials are affected:
- If the latest application to the Swedish Medicines Agency was submitted before January 31, 2022, the repealed Biobank Act applies.
- If the latest application to the Swedish Medicines Agency was submitted between January 31, 2022 and January 31, 2023, the sponsor can choose to request that the application should be processed under the repealed Biobank Act.
The term application includes both initial application, substantial modification and transfer to CTR.
Feel free to contact us for advice in your specific case.
Biobank samples are involved
When a clinical trial of medicinal products includes biobank samples, it always 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 regions.
The sponsor is responsible for contacting a biobank in one of the participating regions early in the process, with a request to take the responsibility for the sample collection. Regardless of whether the responsible biobank belongs to a region or not, the sponsor is responsible for ensuring that document T7a is completed and signed by the relevant biobank custodian.
T7a is then used to notify regions where newly collected biobank samples are taken, that a biobank with another principal will establish and be responsible for these samples. The biobank custodian at the responsible biobank is responsible for sending T7a to the biobanks in each concerned region before the collection of samples will start. If samples will be established in a biobank in the same region where they are collected, T7a does not need to be used.
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 a RBC on the same day as Part II of the application for clinical trial is submitted into CTIS.
When the biobank application is assessed by an RBC prior to the approval of the clinical trial, the evaluation process can be accelerated. Potential completion of information for the biobank application can be handled during the assessment in CTIS, and the establishment of an agreement can be executed faster. Read more about the application process for access to biobank samples under the headline, “The process of the biobank application in clinical trials of medicinal products“.
The process of the biobank application in clinical trials of medicinal products
Prior to submitting the biobank application
- Contact RBC 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 at biobanksverige.se/en/documents/ under the toggle menu called “Clinical trials/performance studies”. - Send the un-signed biobank application to kliniskaprovningar@biobanksverige.se at the same time as the application for a clinical trial of medicinal product is registered into CTIS.
Assessment of the biobank application
- RBC validates and assesses the biobank application. If the application includes existing pathology/cytology samples a feasibility assessment is made by a pathologist.
Please note: RBC will only give guidance regarding the biobank application directly to the sponsor. All communication regarding the clinical trial application shall go through CTIS.
If completion of information is needed for the application of clinical trial and/or the biobank application
- RBC sends the potential request for completion of information regarding the biobank application, including deadline, to the sponsor by e-mail.
- Sponsor submits the completion of information regarding the biobank application.
Final assessment of the biobank application
- If existing samples are to be released, RBC prepares the form for release of samples (T1.2).
- After the approval of the clinical trial, RBC sends the cover page (TY5) with the final assessment, instructions and the application form (T1.1/T1.2/L1a/L1b) to the sponsor with a request to amend potential considerations.
Approval of the biobank application
Following the approval of the clinical trial from CTIS, the sponsor must send all signed biobank applications to the RBC or the biobank, according to the instruction in the cover page, so that authorised representatives of the biobank can approve the biobank agreement.
The following applies for assessed biobank applications:
- The sponsor is recommended to send the signed biobank application to an RBC or the biobank as soon as possible, or, at the latest, three weeks after the approval of the clinical trial.
- The cover page from an RBC shall be appended to the biobank application when sent to the biobank for decision.
- The number of original copies of every application that shall be sent over depends on the number of signing parties.
- Remaining documentation does not need to be enclosed but is already sent to the appropriate biobank by an 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 is not valid until the biobank application and all appendices, if any, are signed by sponsor and approved and signed by an authorised representative of the biobank.
Request of alterations of the biobank agreement
If a request for substantial modifications of a clinical trial 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 a clinical trial before it was submitted to CTIS (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.
The request for alterations to the biobank is made on form T1 and/or T1a if the initial application was made on form T1/T1a and on form T1.1 if the initial application was made for T1.1.
* 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 also welcome to contact us by e-mailing:
kliniskaprovningar@biobanksverige.se