Clinical trials on medicinal products for human use according to Clinical Trials Regulation (CTR)
As of January 31st, 2022, the new 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 new regulation, 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 Biobanks in Medical Care Act applies, an assessment is also made by an RBC. The RBC gives a statement to the Swedish Ethical Review Authority concerning objections regarding patient information and informed consent, and to the Swedish Medical Products Agency concerning other issues. The statement from RBC is taken into consideration 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 new regulation, visit the Swedish Medical Products Agency’s webpage
Documentation for application for clinical trial
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:
Transitional rules and the transfer of active clinical trials
From January 31, 2023, it is no longer possible to apply according to the old directive (2001/20/EC)/national legislation. If you already have an ethical approval – apply for access to samples with document N1a/N1b for biobank application according to multicenter principle with newly collected samples or L1 and potential attachments if not according to multicenter principle.
Transfer of active clinical trials
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 shall be accurate as to the responsibilities of the clinical trial. 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 principal/national coordinating investigator) who applied for ethical approval from the Ethical Review Authority and access to samples from the biobank/RBC and a sponsor who 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 transferred to the sponsor from the principal/national coordinating investigator.
Transfer of biobank agreements: The sponsor who is now responsible must be specified in T1 together with details of the trial (sections 1, 2 and 4), the rest is left blank. Completed T1 is sent to: email@example.com together with previously approved biobank agreement. The National Coordinator at RBC announces how signing should be done. RBC notifies current biobanks and/or RBC of the takeover of biobank agreements, but it does not need to be approved by the biobank manager or equivalent.
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.
If a request for substantial modifications of a clinical trial (transferred into CTIS) 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 RBC through the joint channel of communication for clinical trials (firstname.lastname@example.org). Please note, 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 L1 or N2 (for agreements according to the multicentre principle, N1a).
* 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 time period for the clinical trial in Sweden.
The biobank application
When a clinical trial of medicinal products includes biobank samples a biobank application, approved by the biobank custodian, is required. Something that is new, as a result of the new regulation (EU No 536/2014), is that the biobank application shall be submitted to a Regional Biobank Centre (RBC) the same day as Part II of the application for clinical trial is submitted into CTIS.
When the biobank application is assessed by RBC prior to the approval of the clinical trial the process is sped up. 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 trial of medicinal products“.
The process of the biobank application in clinical trial 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 mailing email@example.com.
- Complete forms T1 and T1a. If the application includes existing samples, form L1a and/or L1b is also to be completed. All forms can be found on Biobank Sweden’s document page under “Research – Documents in English”.
- Send the un-signed biobank application to firstname.lastname@example.org at the same time as the application for 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
- RBC prepares the agreement (T1b and/or T1c – not to be completed by sponsor).
- RBC informs if the multicentre principle is applicable and if there is a need to establish an N4 with private care givers.
- RBC sends the cover page (TY5) with the final assessment, instructions, the main application form (T1) and the proposal for the agreement (T1n and/or T1c) to the sponsor with the request to amend potential objection.
Approval of the biobank application
Following the approval of the clinical trial from CTIS the sponsor shall send all signed biobank applications to RBC or the biobank, according to the instruction on the cover page, so that authorised representative of the biobank of the healthcare principal or the head of RBC can approve the biobank agreement. The following applies for assessed biobank applications:
- The sponsor is recommended to send the signed biobank application to 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 RBC shall be appended to the biobank application when sent to the biobank of the healthcare principal or RBC 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 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 approved and signed by an authorised representative of the biobank of the healthcare principal and/or the head of RBC.
- What is new with the regulation regarding clinical trials of medicinal products, EU No 536/2014?
- What is new regarding the biobank application in connection with the new regulation?
1. What is new with the regulation regarding clinical trials of medicinal products, EU No 536/2014?
- Applications for clinical trials are to be submitted and uploaded to CTIS. The European Medicines Agency (EMA) is responsible for CTIS.
- In Sweden:
- The assessment of the application for clinical trial is coordinated by the Swedish Medical Products Agency and the Swedish Ethical Review Authority. The ethical approval is a part of the approval for the clinical trial.
- the Swedish Medical Products Agency will send, in cases where biobank samples are included in a clinical trial, the application for clinical trial to the concerned biobank for a statement. When a region is principal of the biobank the application will be sent to RBC for statement. The statement from RBC concerns the Biobank in Medical Care Act and in cases where existing pathology/cytology samples are included a feasibility assessment by a pathologist is made.
2. What is new regarding the biobank application in connection with the new regulation?
- If biobank samples, covered by the Biobanks in Medical Care Act, shall be included in the clinical trial the sponsor shall send the biobank application to email@example.com at the same time as the application for clinical trial (Part II) is submitted to CTIS.
- The biobank application is assessed by RBC in parallel with the assessment of the application for clinical trial made by the Swedish Medical Products Agency and the Swedish Ethical Review Authority. In cases where existing pathology/cytology samples are included in the clinical trial the biobank application will get a feasibility assessment from a pathologist.
- The regional biobanks will be represented by RBC.
- New application forms for access to biobank samples in a clinical trial that will be processed according to the new regulation can be found here.
You can find additional FAQ on our main page for clinical trials
For questions, please contact
BIOBANK SVERIGE • C/O REGIONALT BIOBANKSCENTRUM MELLANSVERIGE • AKADEMISKA SJUKHUSET • 751 85 UPPSALA