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FAQ – Frequently Asked Questions: Clinical Trials

General

Costs

Where can I find information about the costs of clinical trials?

The fundamental costs associated with clinical trials are levied on clinical trial approval procedures, approval procedures for modifications after authorisation, and annual safety reports. It should be noted that, in addition to these costs levied by the higher federal authority, there are fees charged by the responsible ethics committee. Corresponding information can be found in Annex 3 of the Ordinance on the Procedure Governing Cooperation Among the Higher Federal Authorities and the Ethics Committees in the Evaluation of Applications for Authorisation of Clinical Trials for Medicinal Products for Human Use.

Updated: 22.08.2025

Which fees apply to the approval of non-commercial, investigator-initiated clinical trials?

If a study is conducted without commercial aim and without financial participation or support from non-public bodies or companies, the applicant may apply for a reduction of the regular fee by 25%.

Updated: 22.08.2025

Which fees apply to the approval of clinical trials at the Paul-Ehrlich-Institut?

The costs for the approval of clinical trials are based on the Special Fee Ordinance of the Federal Ministry of Health for the individually attributable services in its area of responsibility (Besondere Gebührenverordnung des Bundesministeriums für Gesundheit für die individuell zurechenbaren Leistungen in seinem Zuständigkeitsbereich, BMGBGebV). Factors that have a significant impact on the fee amount include the type of clinical trial (e.g. whether the study only requires approval in Germany or also in other European Member States) and the effort required to perform the scientific evaluation. For example, higher costs apply to clinical trials using non-authorised investigational medicinal products than to clinical trials using only authorised investigational medicinal products.

Updated: 22.08.2025

What costs are to be expected when submitting an annual safety report?

An annual safety report must be submitted for every clinical trial in accordance with Article 43 of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use. The Paul-Ehrlich-Institut levies costs ranging from 500 euros to 2,500 euros depending on the processing time.

Updated: 22.08.2025

Who is responsible for the financing of the investigational medicinal products in clinical trials?

The funding of investigational medicinal products in clinical trials is to be provided by the sponsor, based on Article 92 of Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use. According to the regulation, the costs of investigational medicinal products, auxiliary medicinal products, medical devices used for their administration and procedures specifically required by the protocol are not to be borne by the subject, unless the law of the Member State concerned provides otherwise.

Updated: 22.08.2025

Who receives the notification of fees and can the notification also be sent to a different contact address?

The sponsor of the clinical trial is always considered to be the party liable for costs incurred for official actions in the context of the clinical trial. The notification of fees is sent to the applicant. If the applicant is not the sponsor of the clinical trial, they are obliged to bring the notification of fees to the attention of the sponsor as the liable party. By way of derogation, a third party can declare the assumption of costs in writing with the application or subsequent submission of documents. This cost assumption declaration must be attached to the application for approval of a clinical trial or subsequent submissions in a separate letter and uploaded to the Clinical Trials Information System (CTIS) under "Proof of Payment".

Updated: 22.08.2025

How is the notification of fees issued under the Clinical Trials Regulation?

Notifications of fees are issued by the Paul-Ehrlich-Institut. The ethics committees submit their fee claims to the higher federal authority, which draws up a joint notification of fees.

Updated: 22.08.2025

Will the Paul-Ehrlich-Institut still send invoices after the procedure is completed?

The Paul-Ehrlich-Institut will send you an invoice after the procedure is completed.

Updated: 22.08.2025

Non-interventional Studies

What are non-interventional studies?

Pursuant to Article 2 (2) (4) of Regulation (EU) No 536/2014, a non-interventional study is a clinical study that is not a clinical trial. This definition of the non-interventional study was also incorporated into the Medicinal Products Act (section 4 subsection 23 sentence 2 AMG). The obligation to notify the competent higher federal authorities applies when carrying out non-interventional studies in the following categories:

  • non-interventional studies in accordance with section 67 subsection 6 of the AMG and
  • non-interventional post-authorisation safety studies in accordance with section 63f of the AMG.

Updated: 31.01.2025

Which studies are considered non-interventional studies (German - Anwendungsbeobachtungen, AWB)?

A non-interventional study is a study designed to gather insights into the use of authorised or registered medicinal products. Non-interventional studies (AWB) are a subset of non-interventional trials within the meaning of section 4 subsection 23 sentence 3 of the Medicinal Products Act (AMG), i.e. studies in which "findings from the treatment of persons with medicinal products are analysed using epidemiological methods; the treatment, including the diagnosis and monitoring, does not follow a predetermined trial protocol, but only medical practice; if a medicinal product is used that requires marketing authorisation or to approval pursuant to section 21a (1) of the Medicinal Products Act (AMG), the treatment shall be carried out according to the specifications regarding its use contained in the marketing authorisation or approval." The decision to include a patient in a non-interventional study is separate from the decision on the prescription of the medicinal product.

A non-interventional study is not a clinical trial in accordance with section 4 subsection 23 sentence 1 AMG and is therefore not subject to approval. However, pursuant to section 67 subsection 6 of the AMG, the following authorities must be immediately notified: the National Association of Statutory Health Insurance Physicians (Kassenärztlichen Bundesvereinigungen), the National Association of Statutory Health Insurance Funds (Spitzenverband Bund der Krankenkassen), the Association of Private Health Insurance Funds (Verband der Privaten Krankenversicherung e.V.) and the competent higher federal authority. Non-interventional studies are not studies in humans after the authorisation of a medicinal product. Such studies are intended to investigate or demonstrate the clinical or pharmacological effects of medicinal products, to detect side effects, or to investigate the absorption, distribution, metabolism or excretion and are to be carried out with the aim of proving the safety or efficacy of the medicinal products. The treatment of patients, including diagnosis and monitoring, goes beyond the usual medical practice in such studies. These studies are to be carried out as clinical trials in accordance with section 4 subsection 23 sentence 1 of the AMG. Characteristics of a clinical trial include a systematic, randomised allocation of patients to treatment arms and the use of medicinal products outside their authorised indication. These clinical trials must be approved by the competent higher federal authority before they begin and evaluated positively by the competent ethics committee. Approval by the competent higher federal authority and a favourable assessment by the competent ethics committee are also required for clinical trials conducted within the authorised indication, known as phase IV trials.

Updated: 31.01.2025

What information should be considered with regard to the non-interventional nature of non-interventional studies?

Non-intervention is characterised by the fact that the treatment, including diagnosis and monitoring, is carried out in accordance with the usual medical practice. If a medicinal product is used that is subject to authorisation or approval in accordance with section 21a subsection 1 of the AMG, the treatment shall be carried out according to the specifications regarding its use contained in the marketing authorisation or approval.

A medicinal product may not be prescribed for the purpose of including a patient in a non-interventional study. The prescription of a medicinal product and the inclusion of the patient in a non-interventional study must be separated. This separation can be realised if, for example, the patient is identified as a candidate for the non-interventional study after the decision regarding therapy has already been made.

The systematic observation necessary for gaining knowledge requires specifications for collecting data as well as for the nature and scope of the documentation and its control. Depending on the objective of the study, specifications for the treating medical personnel are indispensable in order to obtain sufficiently consistent observations and sufficiently high levels of quality and completeness of the data collected. However, systematic allocation of patients to treatment arms (randomisation) is not permitted. Treatment must be carried out exclusively in accordance with usual medical practice.

In addition, no supplemental diagnostic or monitoring procedures may be used for the patient.

Surveys can be used as a tool in an observational study if their contents do not go beyond the information that would be requested in the context of usual medical practice. The data protection concerns must be observed when conducting such surveys. Pursuant to section 21 subsection 4 of the AMG, the competent higher federal authority decides on the approval obligation of a clinical trial at the request of the competent state authority. This also applies to the differentiation of clinical trials from non-interventional trials. Corresponding differentiation issues must therefore first be addressed to the competent state authority in order to give it the opportunity to comment. The competent state authority will then, if necessary, submit an application for a decision to the competent higher federal authority.

Updated: 31.01.2025

What conditions must a medicinal product meet in order to be studied as part of a non-interventional study?

A non-interventional study is a study designed to gather insights into the use of authorised or registered medicinal products (section 67 subsection 6 sentence 1 of the Medicinal Products Act). Therefore, only data on those medicinal products that are authorised or registered can be collected in a non-interventional study. Data on prescription medicinal products cannot be collected within a non-interventional study.

If a study on prescription medicinal products is planned, a clarification regarding the classification of the study should be made with the competent state authority. The state authorities are responsible for classifying a study as a clinical trial subject to approval and for distinguishing non-interventional studies from clinical trials.

Updated: 31.01.2025

What information must be reported to the higher federal authorities?

The location, time, purpose and observation plan, and the non-interventional study case report forms must be included when submitting a notification. In addition, the current Summary of Product Characteristics of the medicinal product must be enclosed. A final report must be submitted to the competent higher federal authority within one year of the completion of data collection for studies with medicinal products intended for use in humans. This information must be submitted electronically via the AWB notification portal.

The following information must be submitted to the higher federal authorities:

  1. Competent authority: Paul-Ehrlich-Institut, BfArM or both higher federal authorities
  2. Type of study: PASS or non-interventional study
  3. Type of notification: initial notification, notification of amendment, interim report, termination, other Report, or notification of a final report.
  4. Title of the AWB/PASS: informative title with a common term to indicate the study design
  5. Purpose of the AWB/PASS
  6. Planned number of participating doctors for the study as a whole and in Germany.
  7. Where applicable, whether the non-interventional study is carried out at the request of a European regulatory authority, the Federal Joint Committee (G-BA) or another domestic or foreign institution.
  8. Location of study: Germany or multinational
  9. Planned start of data collection: "Start of data collection" refers to the time from which information about the first subject is recorded in the study's data set for the first time.
  10. Planned end of data collection: Indicates the time until which patients are to be observed, i.e. when patient registration forms are to be completed.
  11. Study number of the AWB/PASS
  12. Information about the notifier: institution, name, address (postal address as well as email address and telephone number), as well as the sponsor of the AWB/PASS, if the notification and AWB/PASS is carried out on behalf of another company, such as a pharmaceutical company.
  13. Medicinal products involved as specified in the observation plan.
  14. Observation plan and case report form (CRF) for the AWB stating the reference number of that version and the date of the last version (as an unprotected PDF document, please no scanned image files) as well as the Summary of Product Characteristics (if individual preparations or active substances are observed). The submitted observation plan is published by the higher federal authority in the joint database:

    - in the case of individual preparations, indication of the name of the medicinal product, the INN name(s) and the associated German 7-digit ATC code and the authorisation number,
    - when observing all authorised preparations for an active substance, indication according to the observation plan of the INN name(s) and the 7-digit ATC code,
    - when observing all authorised preparations of substance classes according to the observation plan, indication of the 5-digit ATC code(s) and the name of the substance class(es),
    - in the case of non-specific recording of data regarding all of a patient's prescribed medicinal products without recording of specific preparations or substance classes, information on the type of recording and the recorded medicinal products.

  15. A statistical analysis plan (SAP), if applicable.
  16. The final report of the observational study (as an unprotected PDF document, please no scanned image files), if applicable. The submitted final report is published by the Paul-Ehrlich-Institut or BfArM in the joint database.
  17. Confirmation of the accuracy of the information, a confirmation that the notifier is entitled to make the notification and is aware of the publication of the information and submitted documents in an online portal.
  18. When submitting the final report, a confirmation that the submitted final report is submitted in accordance with the requirements of section 42b subsection 3 sentences 1 and 4 of the AMG, if applicable. After that, the report must include all results, regardless of whether they are favourable or unfavourable. With the exception of the name and address of the pharmaceutical entrepreneur or the sponsor, as well as the name and the address of the consenting investigators pursuant to section 4a of the Federal Data Protection Act, no personal, and especially no patient-related data may be contained in the report.

Updated: 31.01.2025

How do the higher federal authorities publish notifications in accordance with section 67 subsection 6 of the AMG?

The higher federal authorities publish the notifications in accordance with section 67 subsection 6 of the AMG via a joint online portal.

Database of the Paul-Ehrlich-Institut and the Federal Institute for Drugs and Medical Devices (BfArM)

Updated: 31.01.2025

What content is published by the higher federal authorities?

Notifications, observation plans, and final reports submitted for non-interventional studies are made available to the public via the AWB and PASS notification portal. This also applies to the observation plans submitted with the initial notification of a non-interventional study. Observation plans and final reports are published in full in addition to the location, time, and purpose of the non-interventional study.

Updated: 31.01.2025

How should notifications regarding non-interventional studies be made to the higher federal authorities?

Please use the joint notification portal of the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) and the Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines, to submit notifications regarding non-interventional studies.

Notification Portal for AWB and PASS

Updated: 31.01.2025

In what format should the observation plan be submitted?

The observation plan should be submitted as a non-copy-protected PDF document in electronic form. Please upload the observation plan to the non-interventional study notification portal.

The observation plan should be drawn up in accordance with the applicable recommendations of known scientific or regulatory guidelines. Corresponding guidelines can be found in resources such as the "Guidelines for Good Pharmacoepidemiology Practices" (GPP) of the "International Society for Pharmacoepidemiology" (ISPE), the recommendations of the "ENCePP Guide on Methodological Standards in Pharmacoepidemiology", or the Guidelines for Good Epidemiological Practice (GEP) of the German Society for Epidemiology (DGEpi). The corresponding recommendations and models for protocols for non-interventional post-authorisation safety studies in accordance with GVP Module VIII or Commission Implementing Regulation (EU) No 520/2012 can also be used as a basis for protocol development.

Further Information

Notification Portal for AWB and PASS

Updated: 31.01.2025

Should notifications be submitted regarding amendments to the observation plan?

Since the provisions of section 67 subsection 6 sentence 1 AMG are aimed at "conducting" studies, changes to the location, time, purpose, and observation plan made while the study is being conducted must also be implicitly reported to the competent higher federal authority.

A notification of a significant amendment is sufficient. This is understood to mean such amendments that are likely to affect the safety, physical health, or mental health of the participants or are likely to influence the study results or their interpretation, such as a change in primary or secondary target variables, changes in the study population, a significant change in the study scope (+/- 10%), changes in the definitions of the main exposure variables, the endpoints, disturbances or changes to the analysis plan. It should be noted that an amendment of the observation protocol must not violate the character of the non-interventional study.

The significant amendment to the initial notification should be specified in the new notification and an updated observation plan should be submitted via the notification portal, which reflects the changes.

Updated: 31.01.2025

How should the final report be submitted?

The final report should be submitted as a non-copy-protected PDF document in electronic form within 12 months of the end of data collection via the notification portal.

When submitting the final report, the information provided for the study at the time of the initial notification must be updated based on the actual data from the completed study (for example, actual number of patients included, etc.).

The final report should be drawn up in accordance with the applicable recommendations of known scientific or regulatory guidelines. Corresponding guidelines can be found in resources such as the STROBE statement (STrengthening the Reporting of OBservational studies in Epidemiology). The corresponding recommendations and models for final reports for non-interventional post-authorisation safety studies in accordance with GVP Module VIII or Commission Implementing Regulation (EU) No 520/2012 can also be used as a basis for protocol development.

The reports must include all results, regardless of whether they are favourable or unfavourable. With the exception of the name and address of the executor, as well as the name and the address of the consenting investigators pursuant to section 4a of the Federal Data Protection Act, no personal, and especially no patient-related data may be contained in the reports. The final reports submitted will be made available to the public by the competent higher federal authority via an online portal.

Updated: 31.01.2025

How does a non-interventional study differ from a post-authorisation safety study (PASS)?

A safety study for a medicinal product intended for use in humans is any study of an authorised medicinal product that is carried out to identify, describe or quantify a safety risk, to confirm the safety profile of a medicinal product or to measure the effectiveness of risk management measures. Further information on the definition of post-authorisation safety studies (PASS) can be found in the guidelines on good pharmacovigilance practice, or in the Good Vigilance Practice (GVP) Module VIII on PASS and in the GVP Module V on risk management plans based on Article 108a of Directive 2001/83/EC.

The concept of a safety study is primarily based on whether the study is originally initiated to address safety concerns. PASS are listed in the risk management plan (RMP) of the medicinal product as an additional pharmacovigilance measure.
Non-interventional safety studies carried out by the marketing authorisation holder are subject to a notification obligation in accordance with section 63f of the AMG and are not to a notification obligation in accordance with section 67 subsection 6 of the AMG.

Information, observation plans, and final reports on voluntary and ordered post-authorisation safety studies in accordance with section 63f of the AMG should be published in accordance with the requirements of GVP Module VIII in the EU-PAS register in accordance with Article 26 Regulation (EC) No. 726/2004 (see www.encepp.eu).

Updated: 31.01.2025

Notification and Approval Procedures under Radiation Protection Law

Are there special forms for the application and notification procedures under radiation protection law?

Yes, there are special forms that must be supplied as attachments.

The forms for application procedures under radiation protection law can be found on the website of the Federal Office for Radiation Protection (Bundesamt für Strahlenschutz, BfS).

The forms for notification procedures under radiation protection law can be found on the website of the Association of Medical Ethics Committees (Arbeitskreis Medizinischer Ethik-Kommissionen, AKEK).

Updated: 26.08.2025

Must radiation applications submitted to the Federal Office for Radiation Protection under the previously applicable law be transferred to the new procedure and system after 1 July 2025?

No, a transfer is not necessary.

Updated: 26.08.2025

How can subsequent modifications to an application be submitted after 1 July 2025?

If you need to modify a radiation application that has been submitted, you must complete a substantial modification entry in the Clinical Trials Information System (CTIS) or the German Medical Device Information and Database System (DMIDS). You do not have to add any old data to the new system.

The Federal Office for Radiation Protection (Bundesamt für Strahlenschutz, BfS) remains responsible for any radiation applications requiring approval under the new law. The procedure here is regulated in section 205 subsection 2a of the Radiation Protection Act (StrlSchG). If you have any questions, please contact the BfS.

Updated: 26.08.2025

Where should radiation applications be submitted if they are subject to both notification and approval?

This configuration no longer exists as of 1 July 2025. As soon as the study includes any aspects that require approval, an approval application must be made in accordance with section 31 of the Radiation Protection Act (StrlSchG).

Updated: 26.08.2025

If an approval application is submitted in accordance with section 31 of the Radiation Protection Act via the Clinical Trials Information System/the German Medical Devices Information and Database Systems, how is communication with the Federal Office for Radiation Protection conducted during the procedure?

The Federal Office for Radiation Protection (BfS) is informed by the higher federal authorities and has access to the application documents. Further communication with the BfS is carried out via email just as before.

Updated: 26.08.2025

Who is responsible for the notification procedure forms in accordance with section 32 of the Radiation Protection Act? Where can I find the forms?

The Association of Medical Ethics Committees (Arbeitskreis Medizinischer Ethik-Kommissionen, AKEK) has created the notification procedure forms in accordance with section 32 of the Radiation Protection Act and published them on its website.

Updated: 26.08.2025

A clinical trial has been recorded via the Clinical Trials Information System or the German Medical Device Information and Database System and has already been approved. A radiation application must be completed in the course of the clinical trial, but a notification and/or application has already been submitted to the Federal Office for Radiation Protection. Do documents need to be transferred in this case?

No, a transfer is not necessary.

Updated: 26.08.2025

A clinical trial has been submitted via CTIS/DMIDS. A radiation application must be completed in the course of the clinical trial. The application or notification will be submitted after 1 July 2025. How should it be submitted?

The submission options depend on the status of the clinical trial. Please contact the Paul-Ehrlich-Institut via email at ct@pei.de.

Updated: 26.08.2025

Who must be notified of the termination of a research project pursuant to section 141 of the Radiation Protection Act as of 1 July 2025?

In accordance with section 141 of the Radiation Protection Act (StrlSchG), notifications in accordance with section 32 of the StrlSchG must be submitted to the Paul-Ehrlich-Institut or the Federal Institute for Drugs and Medical Devices (BfArM), and approval applications in accordance with section 31 of the StrlSchG must be submitted to the Federal Office for Radiation Protection (BfS).

Updated: 26.08.2025

Is the opinion of the Ethics Committee on an approval application forwarded directly to the Federal Office for Radiation Protection or does the sponsor have to submit it themselves?

The opinion of the Ethics Committee is made available to the Federal Office for Radiation Protection (BfS) via an internal database.

Updated: 26.08.2025

Will there be separate approval letters for applications in accordance with the Clinical Trial Regulation or Medical Device Regulation/Medical Device Law Implementing Act and applications in accordance with section 31 of the Radiation Protection Act?

Yes. Applications in accordance with the Clinical Trial Regulation (CTR) or Medical Device Regulation (MDR)/Medical Device Law Implementing Act (Medizinproduktedurchführungsgesetz, MPDG) and applications in accordance with the Radiation Protection Act (StrlSchG) are conducted in separate procedures with different official responsibilities. Separate letters of approval (decisions) are drawn up for each procedure.

Updated: 26.08.2025

Will a written confirmation be issued stating that a radiation application for which a notification has been submitted may be started?

Section 33 of the Radiation Protection Act (StrlSchG) regulates when a radiation application for which a notification has been submitted may be started. An official decision will be issued in the event of prohibition or restrictions, time limitations or conditions, i.e. if the submitted radiation application may not be carried out or may only be carried out under restrictions, time limitations, or conditions.

Updated: 26.08.2025

Documents are submitted in PDF format. Does this also apply to forms edited in track changes mode for modification notifications?

Yes. Please first make your changes in track changes mode and then save the form as a PDF in track changes mode.

Updated: 26.08.2025

How should applications for radiation applications be submitted if the radiation application is to be carried out as part of a study that is not subject to the Clinical Trial Regulation or the Medical Device Regulation/Medical Device Law Implementing Act?

Please submit such applications directly to the Federal Office for Radiation Protection (BfS) in accordance with section 31a subsection 1 sentence 1 no. 3 of the Radiation Protection Act (StrlSchG).

Updated: 26.08.2025

How should applications or notifications be submitted for radiation applications to be carried out in combined studies (medicinal product and medical device)?

If a radiation application requiring approval in accordance with section 31 of the Radiation Protection Act (StrlSchG) or a radiation application requiring the submission of a notification in accordance with section 32 of the StrlSchG is to be carried out in combined studies – i.e. clinical trials that are submitted both in the Clinical Trials Information System (CTIS) and in the German Medical Device Information and Database System (Deutsches Medizinprodukte Informations- und Datenbanksystem, DMIDS) – the application or notification under radiation protection law should only be submitted exactly once. It can be submitted either in CTIS or in DMIDS.

Please note that the selection of the submission location should be made sensibly by the applicant according to the content focus of the study – the Clinical Trials Regulation (CTR) or the Medical Device Regulation (MDR).

Updated: 26.08.2025

Where can I upload application documents in the Clinical Trials Information System (CTIS)? The European Clinical Trials Regulation does not provide any guidance on the procedure.

The cover letter must either state that the applicant is carrying out a notification procedure in accordance with section 32 of the Radiation Protection Act (StrlSchG), also indicating whether radioactive substances or ionising rays are involved, or state that the applicant is applying for approval in accordance with section 31 of the StrlSchG. The documents for the respective procedures must be uploaded in Part II (Section N_Suitability of Facility) of the Clinical Trials Information System (CTIS). It is important that the prefixes required by the Federal Office for Radiation Protection (Bundesamt für Strahlenschutz, BfS) or the Association of Medical Ethics Committees (Arbeitskreis Medizinischer Ethik-Kommissionen, AKEK) are used in the file names. Corresponding information can be found on the website of the AKEK or the BFS, depending on which process is involved.

Updated: 26.08.2025

Will there then be new sections in Part II of the Clinical Trials Information System in which the documents for the notification procedure must be uploaded?

No, there will be no special sections. It is therefore all the more important to adhere to the naming conventions. The documents for the respective procedures must be uploaded in Part II (Section N_Suitability of Facility) of the Clinical Trials Information System (CTIS).

Updated: 26.08.2025

What is the procedure for studies submitted via the Clinical Trials Information System before 1 July 2025 that would require submission of a notification? Does the applicant have to wait until the initial submission has been approved and then submit the notification with a substantial modification?

The submission options depend on the status of the clinical trial. Please contact the Paul-Ehrlich-Institut via email at ct@pei.de.

Updated: 26.08.2025

If there are questions pertaining to radiation protection law during the notification procedure via the Clinical Trials Information System, are they submitted in Part I or Part II?

The documents are submitted in Part II (Section N_Suitability of Facility) in the Clinical Trials Information System (CTIS). Requests for Information (RFIs) are also submitted in Part II.

Updated: 26.08.2025

Are notification procedure modifications sent to the Paul-Ehrlich-Institut or the Federal Institute for Drugs and Medical Devices via the Clinical Trials Information System or via another route?

Modifications concerning notification procedures in accordance with section 32 of the Radiation Protection Act (StrlSchG) must also be submitted via the Clinical Trials Information System (CTIS).

Updated: 26.08.2025

Is initiating a notification procedure in the Clinical Trials Information System via cover letter allowed even if Germany is not a Reference Member State?

Yes, a cover letter is part of the procedure and you can also include information that is necessary on the national level in it.

Updated: 26.08.2025

How should radiation application notifications be carried out for studies with radiation applications subject to notification for which an application was submitted to the Clinical Trials Information System before 1 July 2025, but the procedure has not yet been completed and the Federal Office for Radiation Protection therefore cannot be notified beforehand?

The submission options depend on the status of the clinical trial. Please contact the Paul-Ehrlich-Institut via email at ct@pei.de.

Updated: 26.08.2025

What is the procedure for studies submitted via the German Medical Device Information and Database System before 1 July 2025 that require the submission of a notification? Does the applicant have to wait until the initial submission has been approved and then submit the notification with a "substantial modification"?

In most situations, the applicant must await the approval of the initial submission. Only then can a request for a substantial modification be made. The radiation application notification can be included in the substantial modification submission. Exception: If the ethics procedure has not yet been completed, it may still be possible – depending on the status of the procedure – to subsequently submit the notification under radiation protection law. Please contact your responsible ethics committee.

Updated: 26.08.2025

If there are questions pertaining to radiation protection law during the notification procedure via the German Medical Device Information and Database System, how are they handled?

The Ethics Committee is responsible for addressing aspects pertaining to radiation protection law. As part of the ethics procedure via the German Medical Device Information and Database System (DMIDS), the committee may also ask questions and/or make additional requests pertaining to radiation protection.

Updated: 26.08.2025

Where do applicants upload radiation protection documents in the German Medical Device Information and Database System? What should the documents be named?

The radiation protection documents must be uploaded in the German Medical Device Information and Database System (DMIDS) in the "Clinical Trials and Performance Studies" module (Klinische Prüfungen und Leistungsstudien) as attachment type "70_StS" (radiation protection, Strahlenschutz) under Tab 10 "Attachments" (Anlagen).

Updated: 26.08.2025

If an application for a radiation application requiring approval is submitted via the German Medical Device Information and Database System, does the BfS dossier have to be included in the initial submission?

Yes, all application documents must be uploaded at the beginning as the process is conducted sequentially. The application must be submitted to the Federal Institute for Drugs and Medical Devices (BfArM) and the Federal Office for Radiation Protection (BfS) as authorised by the Ethics Committee.

Updated: 26.08.2025

How do I submit a notification regarding the departure of a radiation protection supervisor pursuant to section 141 subsection 2 no. 1 of the Radiation Protection Ordinance?

The notification should be submitted in the Clinical Trials Information System (CTIS) as a non-substantial modification in accordance with EU Regulation No. 536/2014 Article 81 (9). The departure of the radiation protection supervisor should be communicated in an accompanying letter. Use the subject line: "Departure of radiation protection supervisor at study site xy".

Updated: 20.01.2026

How do I submit a notification regarding the termination of a research project pursuant to section 141 subsection 2 no. 2 of the Radiation Protection Ordinance?

The "End of Trial" notification submitted via the Clinical Trials Information System (CTIS) in accordance with EU Regulation No. 536/2014 Art. 81 (9) and Art. 37 (1) also covers the reporting obligation in accordance with section 141 subsection 2 no. 2 of the Radiation Protection Ordinance (StrlSchV).

Updated: 20.01.2026

How do I submit an immediate notification regarding discontinuation, interruption of use, or change of the benefit-risk ratio pursuant to section 141 subsection 3 no. 1 of the Radiation Protection Ordinance?

If the discontinuation or interruption relates only to the application of radiation or the application of radiation at individual study sites, this corresponds to a substantial modification pursuant to EU Regulation No. 536/2014 Art. 19 and 21. This modification must be reported via the Clinical Trials Information System (CTIS). Please provide information regarding the modification in the accompanying letter.

If the discontinuation or interruption relates to the entire clinical trial, this corresponds to a notification in accordance with EU Regulation No. 536/2014 Art. 37 or 38. The notification obligation pursuant to section 141 subsection 3 no. 1 of the Radiation Protection Ordinance (StrlSchV) is covered by the notification pursuant to Art. 37 or 38 of EU Regulation No. 536/2014.

Updated: 20.01.2026

How should the radiation protection supervisors (e.g. clinical radiology or a participating external radiological practice) be registered initially and how are changes reported?

In accordance with section 32 of the Radiation Protection Act (StrlSchG), details on the radiation protection supervisors do not have to be reported to the competent authority when submitting a notification. Even though there is no reporting obligation, the radiation protection supervisor positions must of course be filled, but a report to the competent authority upon submitting a notification in accordance with section 32 StrlSchG is not necessary. However, if the radiation protection supervisor departs from a multicentre study, the submission of a corresponding notification pursuant to section 141 subsection 2 no. 1 of the Radiation Protection Ordinance (StrlSchV) is mandatory (see FAQ "How do I submit a notification regarding the departure of a radiation protection supervisor pursuant to section 141 subsection 2 no. 1 of the Radiation Protection Ordinance?).

Updated: 20.01.2026

How should I submit notifications for modifications that do not lead to modifications listed in the "Form for Notifications in Accordance with Section 32 StrlSchG" by the Association of Medical Ethics Committees (AKEK)? For example, relevant protocol modifications, extension of the duration of the radiation applications, or insurance changes.

Please report these modifications as a substantial modification (SM) Part II exclusively via the Clinical Trials Information System (CTIS). Submitting a notification by email is not possible.

Updated: 20.01.2026

Which study sites must submit a final report to the relevant supervisory authority? Prior to 1 July 2025, reports were submitted by each site. The process for submissions after 1 July 2025 requires one study-wide report covering all study sites.

A final report is submitted in accordance with section 142 of the Radiation Protection Ordinance (StrlSchV) by the person authorised to carry out the medical research – usually the sponsor – to the competent supervisory authority. In the case of multi-centre studies, the radiation protection supervisors at each study site must provide the required information to the person authorised to carry out medical research.

Updated: 20.01.2026

How can I extend temporarily approved notifications submitted before 1 July 2025?

These modifications must be submitted as a substantial modification via the Clinical Trials Information System (CTIS). The accompanying letter must include information on the earlier notification submitted in accordance with section 32 of the Radiation Protection Act (StrlSchG), including whether radioactive substances or ionising rays are affected by the modification and if the corresponding documents have been uploaded in Part II (Section N_Suitability of Facility). An email must also be sent to ctr@bfarm.de when a substantial modification notification (SM) is submitted in CTIS indicating that these studies also concern the notification procedure initiated in accordance with section 32 of the StrlSchG.

Updated: 20.01.2026

Should an email modification notification only be sent for the first modification notification or for all subsequent modifications as well?

An email to ctr@bfarm.de is only necessary for the first modification notification. This applies to studies whose initial application was submitted and approved before 1 July 2025.

Updated: 20.01.2026

Which fees apply to the submission of a radiation protection notification in connection with the submission of a clinical trial?

The costs for a notification submitted in accordance with section 32 of the Radiation Protection Act (StrlSchG) are based on the Cost Ordinance under the Atomic Energy Act and the Radiation Protection Act (AtSKostV). The Paul-Ehrlich-Institut or the Federal Institute for Drugs and Medical Devices (BfArM) charges a fee pursuant to section 2 subsection 2 no. 7 AtSKostV. This fee claim is sent to the applicant in a joint invoice together with the fee claim for the clinical trial submission (e.g. application for approval of a clinical trial, substantial modification).

However, it should be noted that fee claims from the responsible ethics committee for the submission of notifications pursuant to section 32 of the StrlSchG are sent separately by the ethics committee to the applicant in accordance with section 2 subsection 2 no. 1a AtSKostV. This also applies to fee claims from the responsible ethics committee for approval applications submitted in accordance with section 31 of the StrlSchG.

Updated: 23.01.2026

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