To submit a Clinical Trial Application (CTA) in Europe, you must submit your application through the Clinical Trials Information System (CTIS), the EU-wide portal that has been mandatory for all clinical trial applications since January 2025. The process involves preparing a structured dossier, selecting your participating member states, and completing both Part I (scientific and regulatory content) and Part II (national and ethics requirements) of the application. The sections below walk through each key aspect of the CTA submission process in detail.
What documents do you need to submit a CTA in Europe?
A CTA submission in Europe requires a structured set of documents divided into two parts. Part I covers the scientific and medicinal product information shared across all member states, while Part II contains country-specific documentation, including ethics committee submissions and national regulatory requirements. Together, these documents must give authorities a complete picture of the trial’s design, safety profile, and operational setup.
The core documents required for Part I include:
- Cover letter explaining the nature and scope of the application
- EU application form completed via CTIS
- Investigational Medicinal Product Dossier (IMPD) covering quality, non-clinical, and clinical data
- Investigator’s Brochure (IB) summarizing the clinical and non-clinical profile of the investigational product
- Clinical Trial Protocol including the full study design, endpoints, and statistical methodology
- Summary of the protocol in lay language
Part II documentation typically includes informed consent forms, subject recruitment arrangements, insurance or indemnity certificates, proof of financial arrangements, and documentation of the suitability of investigators and trial sites. Each participating member state may have additional national requirements layered on top of these, so it is important to check country-specific guidance before finalizing your submission package. To learn more about how we support clients through this process, visit our regulatory services overview.
How does the CTIS portal work for CTA submissions?
CTIS is the centralized EU platform where sponsors submit, manage, and track clinical trial applications across all EU and EEA member states. Sponsors create a single application in CTIS, upload all required documentation, and select which member states will participate. The portal then routes the application simultaneously to the relevant national competent authorities and ethics committees for review.
The workflow in CTIS follows a structured sequence. After account registration and organization enrollment, the sponsor creates a new trial workspace, completes the application form, and uploads Part I and Part II documents. Once submitted, the system triggers the validation phase, during which authorities check whether the application is complete before formal review begins.
CTIS also manages the entire post-authorization lifecycle, including substantial modifications, safety reporting, and trial results submission. Familiarity with the portal’s structure before your first submission is strongly recommended, as navigating the document hierarchy and role assignments can be time-consuming without prior experience.
What is the review timeline for a CTA in the EU?
The standard review timeline for a CTA in the EU under the Clinical Trials Regulation (EU No 536/2014) is up to 30 days for the initial assessment phase, followed by a consolidated assessment phase of up to 22 days. Including the validation phase and any clock stops for responses to questions, the total timeline from submission to authorization can range from approximately 45 to 90 days, depending on the complexity of the trial and the number of member states involved.
The timeline breaks down into distinct phases. The reporting member state leads the Part I assessment and produces a consolidated assessment report. Member states then have the opportunity to raise concerns or accept the conclusions. Part II is assessed independently by each member state in parallel. Clock stops occur when authorities request additional information, and these pauses can add several weeks if the sponsor’s responses require significant preparation.
For low-intervention trials or trials with well-established investigational products, timelines tend to be shorter. For first-in-human studies or trials involving complex biological products, sponsors should build additional time into their planning for potential questions and supplementary data requests.
Which EU member states need to be included in a CTA?
You only need to include the EU member states where you actually intend to conduct the clinical trial. There is no requirement to apply in all member states simultaneously. The reporting member state, which leads the Part I scientific assessment, is selected by the sponsor at the time of submission, and that choice has strategic implications for the review process.
Choosing the right reporting member state matters. Some sponsors select member states with strong regulatory expertise in the relevant therapeutic area, faster historical review times, or existing relationships with the competent authority. The reporting member state coordinates the consolidated assessment and communicates with other member states throughout the process, so its regulatory culture and workload can influence the overall experience.
If you plan to expand the trial to additional member states after the initial authorization, you can submit a substantial modification to add new countries. This is a common approach when sponsors want to start quickly in a core set of countries and scale up recruitment later. Our team has extensive experience guiding sponsors through these decisions — find out more on our company page.
What are the most common reasons a CTA gets rejected or delayed in Europe?
The most common reasons for CTA rejection or delay in Europe include an incomplete or poorly structured IMPD, inconsistencies between the protocol and the investigator’s brochure, insufficient non-clinical data to support the proposed dose or patient population, and missing or inadequate national Part II documentation. Administrative errors during CTIS submission, such as incorrect document categorization or missing signatures, can also trigger validation failures that reset timelines.
Beyond documentation gaps, scientific deficiencies are a frequent source of clock stops. Authorities often raise questions about the risk-benefit justification, the adequacy of monitoring plans, or the suitability of proposed trial sites. Sponsors who underestimate the level of detail required in the IMPD quality section, particularly for novel formulations or complex manufacturing processes, frequently receive requests for supplementary data.
Preparation is the most effective mitigation. Conducting a pre-submission review of your dossier against current EMA guidance documents, running internal mock validation checks, and confirming national requirements with each participating member state before submission significantly reduces the risk of avoidable delays.
How does a CTA submission differ for biologics or ATMPs?
CTA submissions for biologics and Advanced Therapy Medicinal Products (ATMPs) follow the same CTIS process as conventional small molecules, but the IMPD requirements are substantially more demanding. For biologics, the quality section must address the complexity of the manufacturing process, characterization of the active substance, comparability data where relevant, and a detailed discussion of immunogenicity risk. For ATMPs, which include gene therapies, somatic cell therapies, and tissue-engineered products, additional requirements around donor testing, traceability, and specific risk assessments apply.
ATMPs in particular require engagement with the EMA’s Committee for Advanced Therapies (CAT) in many cases, and sponsors developing these products are strongly encouraged to seek scientific advice before preparing the CTA dossier. The scientific complexity of ATMPs means that the IMPD often needs to justify unconventional manufacturing steps, limited batch release data at early trial stages, and risk management strategies tailored to the specific modality.
For both biologics and ATMPs, regulatory submissions of this complexity benefit from early alignment with authorities. Pre-submission meetings with the reporting member state’s competent authority can clarify expectations and reduce the likelihood of major questions during formal review, which is particularly valuable given the long development timelines and high costs associated with these product classes.
How Starodub supports your CTA submission in Europe
Navigating a CTA submission in Europe involves detailed documentation, strategic member state selection, and a thorough understanding of CTIS and the Clinical Trials Regulation. We support biopharmaceutical and medical device companies at every step of this process, from initial dossier planning through to authorization and lifecycle management.
Our support for CTA submissions includes:
- IMPD preparation and review for small molecules, biologics, and ATMPs, ensuring the quality, non-clinical, and clinical sections meet current EMA expectations
- CTIS submission management, including document structuring, portal navigation, and validation checks before formal submission
- Reporting member state strategy, helping you select the most appropriate country to lead your Part I assessment
- Part II coordination across multiple member states, including country-specific national requirement checks
- Response to authority questions, drafting clear and scientifically substantiated replies to consolidated assessment reports and national queries
- Substantial modifications for protocol amendments, new member state additions, and safety updates throughout the trial lifecycle
With over 400 completed projects and a team that includes specialists in biologics, ATMPs, and regulatory CMC, we bring both scientific depth and practical submission experience to every engagement. If you are preparing a CTA or want to review your submission strategy, get in touch with our team to discuss how we can support your path to clinical trial authorization in Europe.
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This content was generated with the help of AI and it may contain mistakes
