Step‑by‑step Clinical Trial Authorisation Process in Germany (CTIS, Ethics & National Rules)

Any sponsor planning to conduct a clinical trial involving an investigational medicinal product (IMP) on German territory must complete the clinical trial authorisation process Germany requires under the EU Clinical Trials Regulation. Since 31 January 2023, the Clinical Trials Information System (CTIS) has been the sole submission channel for initial clinical trial applications across the European Economic Area, replacing the former EudraCT‑based workflow. In Germany, a valid authorisation depends on two parallel outcomes: a favourable opinion from a responsible ethics committee and a positive assessment by the competent national authority, either the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) or the Paul‑Ehrlich‑Institut (PEI), depending on product type.

This guide sets out the full procedure, the documents needed, key timelines, indicative costs and common pitfalls that sponsors and regulatory affairs teams face in 2026.

Overview of the Clinical Trial Authorisation Process and Who It Applies To

Regulation (EU) 536/2014, the Clinical Trials Regulation (CTR), governs the authorisation, conduct and oversight of clinical trials of medicinal products for human use throughout the EEA. The regulation applies to all interventional studies involving an IMP, including trials of chemical entities, biologics, vaccines, gene‑therapy products and advanced‑therapy medicinal products (ATMPs). Non‑interventional studies, compassionate‑use programmes and studies involving medical devices (rather than medicinal products) fall outside its scope.

Under the CTR, the sponsor bears primary regulatory responsibility. Both commercial pharmaceutical companies and non‑commercial academic sponsors must submit through CTIS. Where a trial includes sites in Germany, the sponsor must satisfy Germany’s national requirements in addition to the coordinated EU assessment. This dual requirement, central CTIS submission plus national validation, is the defining feature of the clinical trial authorisation process Germany applies in practice.

When to Use CTIS for Initial Applications

CTIS is mandatory for every initial clinical trial application submitted to any EEA Member State. The former EudraCT database is no longer used for new submissions. Sponsors access CTIS through the EU Clinical Trials portal, where they create a sponsor workspace, register their organisation, and prepare the structured application dossier. EudraCT numbers may still appear in legacy references, but all new applications and substantial amendments are filed exclusively through CTIS.

Eligibility and Prerequisites for the Clinical Trial Authorisation Process in Germany

Before a sponsor can submit a clinical trial application, several eligibility conditions and prerequisites must be satisfied. The CTR permits any legal entity established in the EEA to act as sponsor. Non‑EU sponsors may apply, but they must designate an EU‑based legal representative who assumes the sponsor’s obligations under the regulation. The sponsor must also ensure that trial insurance or an equivalent indemnity arrangement is in place to cover participant liability, a requirement that German national practice enforces strictly.

The application covers all interventional trials involving an IMP. Trials of authorised medicinal products used within their marketing‑authorisation terms (non‑interventional studies) do not require a CTA. Compassionate‑use programmes are governed by separate national procedures. A trial triggers the German CTA requirement whenever at least one investigator site is located in Germany, regardless of where the sponsor is established.

Which Authority Is Competent in Germany?

Germany splits competent‑authority responsibilities by product type. BfArM assesses applications for trials involving chemical medicinal products and most small‑molecule drugs. PEI is responsible for trials involving vaccines, sera, blood products, tissue preparations, allergens, gene‑therapy medicinal products, somatic cell‑therapy products and other ATMPs. Sponsors must identify the correct authority before submission; mis‑routing causes delays and potential validation failure.

Ethics Committee Requirement and Local Considerations

A favourable opinion from a responsible ethics committee is a mandatory prerequisite for authorisation under the CTR. In Germany, the responsible ethics committee is determined by the location of the coordinating investigator. For multicentre trials, one lead ethics committee issues the primary opinion, but individual site ethics committees (at the respective Landesärztekammer or university) may be consulted on site‑specific matters. Sponsors must prepare German‑language informed consent forms and patient information for each participating site. Both the competent authority authorisation and the ethics committee opinion must be obtained before any trial activities may begin.

Step‑by‑Step Clinical Trial Authorisation Procedure

The following six steps describe the application workflow from initial preparation through post‑authorisation obligations. The timeline table at the end of this section summarises each step, the responsible actor and the typical duration.

Step 1: Pre‑Submission Preparation

The sponsor must register its organisation in CTIS before any application can be created. Registration requires an EMA Account, which any authorised individual can create through the EMA Account Management portal. The sponsor’s organisation must then be verified and linked to the CTIS sponsor workspace. Typical verification takes 2–7 days, but complex organisational structures or first‑time registrations can require up to 30 days.

During this phase, the sponsor assigns user roles within the CTIS workspace, regulatory affairs staff, medical monitors, CRO personnel, and configures access permissions. If a contract research organisation (CRO) will manage the filing, the CRO’s users must be granted delegate access within the sponsor workspace.

Translation planning begins here. Germany requires that certain national‑annex documents, informed consent forms, patient information leaflets and, in some cases, protocol synopses, be submitted in German. Sponsors should commission certified translations early, as delays in this step frequently cascade into the validation phase.

Step 2: Draft the Clinical Trial Application Dossier

The CTIS application is structured into modules. Part I of the application (assessed jointly by all concerned Member States) includes the clinical protocol, the Investigator’s Brochure (IB), the Investigational Medicinal Product Dossier (IMPD) and the structured EudraCT data set entered directly into CTIS. Part II (assessed nationally) includes country‑specific documents such as informed consent forms, investigator CVs, GCP certificates, insurance evidence and ethics committee submission forms.

For Germany, the national annex in Part II must contain the documents required by BfArM or PEI (depending on product type) and the responsible ethics committee. These typically include German‑language informed consent forms, site‑specific investigator qualifications, evidence of clinical trial insurance meeting German statutory requirements and any BfArM/PEI templates or supplementary forms.

Sponsors should use the latest versions of protocol templates and ensure strict version control across all documents. Every document uploaded to CTIS must carry a date and version number. Inconsistent versioning is one of the most common causes of validation queries.

Step 3: Submit the Initial Application via CTIS

The sponsor creates a new clinical trial application in the CTIS sponsor workspace. The application form requires the sponsor to designate a Reporting Member State (RMS), the country that will coordinate Part I assessment, and one or more Member States Concerned (MSCs). If Germany is not the RMS, it is designated as an MSC, and its national documents are attached under the Germany‑specific Part II section.

Once the application is submitted, CTIS automatically routes it to all designated Member States. In Germany, the competent authority (BfArM or PEI) and the responsible ethics committee each receive access to the relevant application modules. The date of successful submission is recorded as Day 0 of the regulatory timeline.

Sponsors should confirm that all attachments have uploaded correctly and that the CTIS status shows a validated submission. Technical upload failures, corrupted PDFs, oversized files, misnamed documents, can delay the start of the regulatory clock.

Step 4: National Validation and Ethics Committee Review

After submission, Member States perform a completeness and validation check. Under the CTR, this validation phase is designed to confirm that all required documents are present and that the application is formally admissible. In Germany, BfArM or PEI reviews the Part I and Part II dossier components relevant to its competence, while the responsible ethics committee checks the national‑annex documents.

The validation window in German practice typically spans 10–21 days, depending on the authority and the trial’s complexity. If the dossier is incomplete, the authority or ethics committee issues a request for information (RFI) through CTIS. Each RFI triggers a clock‑stop: the regulatory assessment clock pauses until the sponsor provides a satisfactory response.

Once validation is complete, the coordinated Part I assessment phase begins. The RMS leads the scientific evaluation over a standard period of 45 days (extendable in defined circumstances), and MSCs, including Germany, provide national input. The ethics committee conducts its parallel review of Part II matters, including informed consent, participant recruitment and data protection arrangements.

Sponsors should allocate a dedicated rapid‑response team for RFIs. Late or incomplete responses can prolong the procedure significantly and, in the worst case, lead to a negative coordinated decision.

Step 5: Authorisation Outcome and Start‑of‑Trial Notifications

A positive outcome requires both a favourable ethics committee opinion and a national competent authority authorisation for Germany. If the RMS and MSCs reach a positive Part I conclusion and Germany’s Part II assessment is also favourable, Germany issues its national authorisation through CTIS. The decision is recorded on the EU Clinical Trials Register and becomes publicly accessible.

Before recruiting the first participant at any German site, the sponsor must submit a start‑of‑trial notification. This notification confirms that site‑level arrangements, investigator agreements, pharmacy readiness, local ethics acknowledgement, are in place. The notification is typically filed through CTIS and copied to the responsible ethics committee.

Step 6: Post‑Authorisation Obligations

Authorisation is not the end of the regulatory process. Throughout the trial, the sponsor must comply with ongoing reporting and amendment obligations under the CTR. Suspected unexpected serious adverse reactions (SUSARs) must be reported to the EudraVigilance database. Fatal or life‑threatening SUSARs require an initial report within 7 days, with follow‑up information provided within a further 8 days. All other SUSARs must be reported within 15 days.

The sponsor must submit a Development Safety Update Report (DSUR) annually, in accordance with CTR and ICH E2F schedules. Any change to the protocol, investigator team, IMP manufacturing or trial design that qualifies as a substantial amendment must be notified through CTIS. Member States, including Germany, have defined review periods for substantial amendments.

Required Documents and Information for a Clinical Trial Application in Germany

A complete application dossier must satisfy both the CTIS Part I/Part II structure and Germany’s national‑annex requirements. The table below consolidates all key documents needed, indicating who prepares each document, the expected format and any Germany‑specific notes. Documents marked as “CTIS‑hosted” are entered or uploaded directly into the CTIS platform. Documents marked as “National annex” are attached under the Germany‑specific Part II section.

Translation and version control. All participant‑facing documents, ICFs, patient information leaflets and recruitment materials, must be submitted in German for sites located in Germany. E‑signatures are accepted in CTIS, but certain ethics committees may require wet‑ink originals for specific forms. Sponsors should confirm the signature policy of the responsible ethics committee before submission.

CTIS‑hosted versus national annex. Part I documents (protocol, IB, IMPD) are uploaded centrally and assessed by all concerned Member States. Part II documents (ICFs, investigator qualifications, insurance, ethics forms) are country‑specific and reviewed only by the national competent authority and ethics committee for that Member State.

Timeline and Key Deadlines for the Clinical Trial Authorisation Process in Germany

The CTR establishes a structured regulatory timeline for the coordinated assessment of clinical trial applications. Under Regulation (EU) 536/2014, the standard initial assessment period is set at a combined total that, including validation and Part I/Part II review, should not exceed approximately 60 days from validated submission to final Member State decision, subject to clock‑stops triggered by RFIs.

In German practice, the national validation check typically takes 10–21 days. During this window, BfArM or PEI confirms the completeness of both Part I and Part II documents, and the responsible ethics committee verifies receipt of its required national‑annex materials. If validation queries arise, the clock stops until the sponsor responds satisfactorily.

Clock‑stops are the single largest source of timeline uncertainty. For minor queries, a missing CV, a formatting error, sponsors are typically expected to respond within 7–14 days. For major scientific or safety queries, the expected response window extends to 21–30 days. Each day of clock‑stop adds directly to the total elapsed time. Industry observers expect that in 2026, the average total elapsed time from CTIS submission to national authorisation in Germany, including clock‑stops, is 2–4 months.

Costs, Fees and Tax Considerations

The total cost of securing a clinical trial authorisation in Germany varies widely depending on the trial’s complexity, the number of sites and whether the sponsor uses a CRO. Germany’s regulatory fee structures differ from those in some other EEA Member States: competent authority fees for initial CTA assessment are set by BfArM and PEI under their respective fee schedules, and ethics committee fees are determined independently by each Landesärztekammer. Sponsors should verify current fee amounts directly with the relevant authority and ethics committee before budgeting.

The table below provides indicative cost ranges. All figures are approximate and subject to change; they should be confirmed against the current fee schedules published by BfArM, PEI and the responsible Landesärztekammer.

What Changes in 2026: CTR, CTIS and National Validation Updates

The transition from the former EU Clinical Trials Directive (2001/20/EC) to Regulation (EU) 536/2014 reached its practical completion between 2022 and 2025. Since 31 January 2023, CTIS has been the mandatory submission route for all initial clinical trial applications in the EEA, and EudraCT‑based submissions are no longer accepted for new trials. By 2026, the operational maturity of CTIS has improved, but sponsors still encounter system updates, evolving user‑interface changes and periodic maintenance windows that can affect submission timing.

In Germany, several practical developments shape the 2026 landscape. The BfArM and PEI have progressively standardised their national‑annex expectations, reducing, but not eliminating, variation in the documents and formats they require. Ethics committees across the Länder have moved toward greater digitisation of their review processes, though the degree of digital readiness varies by region. Early indications suggest that stricter organisation‑registration checks within CTIS are leading to longer initial verification times for sponsors registering for the first time.

The German Medizinforschungsgesetz (MFG), the Medical Research Act, introduced changes intended to streamline national clinical‑trial procedures and align German practice more closely with the CTR framework. The likely practical effect is a more standardised national validation process and clearer rules on the division of responsibilities between the competent authority and ethics committees. Sponsors planning submissions in 2026 should review the latest BfArM, PEI and ethics committee guidance to confirm current procedural requirements.

Common Pitfalls in the Clinical Trial Authorisation Process and How to Avoid Them

• Incomplete national annex or missing German translations. The most frequent cause of validation failure in Germany is submitting Part II documents without German‑language ICFs, patient information or required local templates. Mitigation: commission certified translations during dossier assembly and perform a pre‑submission completeness check against the relevant ethics committee’s template requirements.
• Mis‑routing submissions to the wrong competent authority. Submitting a vaccine trial to BfArM instead of PEI (or vice versa) causes rejection at the validation stage. Mitigation: confirm the IMP’s product classification against the BfArM/PEI competence split before selecting the competent authority in CTIS.
• Missing or inadequate insurance coverage. German national requirements for clinical trial participant insurance are strict. A policy that satisfies one Member State’s requirements may not meet Germany’s statutory minimums. Mitigation: obtain a German‑law compliant clinical trial insurance certificate and have it reviewed by local counsel before submission.
• Delayed CTIS organisation verification. First‑time sponsor registrations in CTIS can take up to 30 days. If verification is not complete before the target submission date, the entire timeline shifts. Mitigation: begin CTIS registration at least 6 weeks before the planned submission date.
• Late or incomplete responses to RFIs. Every day of delay in responding to an RFI extends the clock‑stop and the total elapsed time to authorisation. Repeated or unsatisfactory responses can lead to a negative coordinated decision. Mitigation: assign a dedicated RFI rapid‑response team with authority to approve responses within 48 hours of receipt.
• Ethics committee heterogeneity across Länder. Requirements for site‑specific documentation, fee amounts and review timelines vary between the ethics committees of different German states. Mitigation: appoint a local regulatory coordinator for each Land and maintain a central checklist of each committee’s requirements.

Appealing a negative decision. If Germany issues a negative national decision, either a refusal of competent‑authority authorisation or an unfavourable ethics opinion, the sponsor may have recourse to administrative objection procedures under German administrative law. The specific procedure, applicable deadlines and prospects of success depend on the grounds for refusal and the authority involved. Sponsors facing a negative outcome should engage experienced regulatory counsel promptly, as objection deadlines can be short.

Sources

1. European Commission / EUR‑Lex, Regulation (EU) 536/2014 (Clinical Trials Regulation)
2. EMA, CTIS / EU Clinical Trials (CTIS for sponsors)
3. BfArM, Clinical trials (Germany)
4. Paul‑Ehrlich‑Institut (PEI), Clinical trials
5. EudraCT / EMA EudraCT FAQ
6. ClinicalTrialsRegister.eu (EU Clinical Trials Register)
7. Charité Study Center guidance (operational checklists)
8. PMC / NCBI, CTR/CTIS implementation experiences
9. Lexology, German clinical trial application guidance
10. German Legal Code, Arzneimittelgesetz (AMG)