Clinical Trial Application

 

Submission of a Clinical Trial Application

The Clinical Trials Information System (CTIS) is the single entry point for the submission of information relating to clinical trials in the European Union (EU) and the European Economic Area (EEA).

CTIS includes a workspace for clinical trial sponsors and the organisations working with them, a workspace for the authorities of EU Member States and EEA countries and the European Commission, as well as a public page.

CTIS is available on the European Union clinical trials website. To support the use of CTIS, an online support service is available - CTIS Service Desk - or you may contact them by email at: ServiceNow@ema.europa.eu.

If you are a non-commercial sponsor, please submit your query by opening a service request on the CTIS Service Desk and indicating that you are a non-commercial sponsor in the corresponding field ('User affiliation').

 

How are clinical trials processed in CTIS?

Clinical trial sponsors wishing to obtain regulatory approval for a clinical trial in one or more EU Member States and EEA countries must submit a single clinical trial application form and an application dossier through CTIS. The submission of the single clinical trial authorisation application form and the application dossier will also include the public registration of the clinical trial.

CTIS enables the day-to-day process management of EU Member States, EEA countries and sponsors throughout the clinical trial lifecycle. CTIS will ensure the regulatory oversight functions of clinical trials as well as the supervision and monitoring tools.

 

 

How to prepare for CTIS

Sponsors may consult the CTIS Handbook for sponsors for guidance on preparing for CTIS.

You may also find information on CTIS training and support in training sessions made available by the EMA: (bitesize talks, walk-in clinics, webinars, events for academia and demonstrations).

In the newsletter "Clinical Trials Highlights", you can find important information and updates on clinical trials and also on CTIS.

 

 

How to prepare the submission of the application?

For information on guidance documents on the submission and assessment of clinical trials, application templates, and question-and-answer documents, you may consult the CTCG page: «https://www.hma.eu/about-hma/working-groups/clinical-trials-coordination-group.html»

For information on the documents required to be included in a clinical trial authorisation application, please consult Annex I of the European Clinical Trials Regulation.

For information on the registration of investigational medicinal products in the Extended EudraVigilance Medicinal Product Dictionary, you may consult the EMA page on this topic: XEVDPM

 

To prepare your applications by anticipating possible questions that may be raised during the assessment, please consult the selected list of the most frequent and relevant considerations raised during the assessment of clinical trial authorisation applications in the document "Frequent issues identified during Part I and Part II assessments".

To better prepare your application, you may request scientific advice prior to submission:

  1. Pre-CTA advice pilot
  2. SAWP CTCG pilot on scientific advice
  3. Regulatory and Scientific Advisory Office (GARC)
  4. Simultaneous National Scientific Advice (SNSA)
  5. ETF scientific advice that facilitates clinical trial authorisations (SA-CTA)

For more information on scientific advice, you may consult the mapping of available Scientific Advice options on the Accelerating Clinical Trials in the EU (ACT EU) page.

 

Timelines

The timelines for the assessment of a clinical trial application under Regulation (EU) No. 536/2014 are harmonised across the European Union through the CTIS (Clinical Trials Information System).

The standard assessment process generally takes up to 60 days, but this period may be extended if there are requests for additional information (RFI).

 

Aplication Phases and Timelines

The assessment is divided into three main stages:

  1. Validation (up to 10 days): Verification that the application is complete and falls within the scope of the regulation.
    • If there are requests for additional information (RFI): The sponsor has 10 days to respond, and Member States have 5 days to review the response (totalling +15 days).
  2. Assessment of Part I and Part II (up to 45 days):
    • Part I: Scientific and regulatory aspects common to all Member States (coordinated by the Reporting Member State).
    • Part II: Country-specific ethical aspects (in Portugal, assessed by the Ethics Committee for Clinical Research (CEIC)).
    • If there are requests for additional information (RFI): The timeline may be extended by a maximum of 31 days (12 days for the sponsor's response and 19 days for the final assessment by the authorities).
  3. Decision (5 days): Notification of the final decision following the conclusion of the assessment.

Note: In the case of the assessment of applications for trials involving advanced therapy medicinal products (ATMPs), the assessment period may be extended by a further 50 days.

 

Fees

The procedures for obtaining authorisation from INFARMED, I.P. and a favourable opinion from CEIC require the payment of a fee, according to the type of study, and the submission of the documentation required for the clinical trial application or substantial modification. Ministerial Order No. 63/2015, of 5 March, sets the fees applicable to acts carried out under Law No. 21/2014, of 16 April, as amended by Law No. 73/2015, of 27 July.

Following the submission of clinical trial applications and substantial modifications in the Clinical Trials Information System (CTIS), the links relating to fee payment and fee exemption requests will be made automatically available to the respective EU contact point identified in CTIS. A manual with further details on this new procedure has been made available.

 

Fee Exemption

In accordance with the provisions of paragraph 3 of Article 26: "Non-commercial clinical trials, as well as clinical trials in which the sponsor is the investigator, are exempt from payment of the fees referred to in paragraph 1."

 

Applicable Regulation:

Regulatory provisions applicable to the submission of applications for the conduct of a Clinical Trial as well as applications for Substantial Modification, Notification of Clinical Trial Completion and Final Report, and other Notifications: