Before a medicinal product may be tested in humans in the European Union, the clinical trial needs an authorisation. Since Regulation (EU) No 536/2014, the sponsor submits a single clinical trial application (CTA) for this via the EU portal CTIS, which covers all Member States in which the trial is to take place. One Member State takes the lead as the reporting Member State, the others contribute to the assessment, and in the end each Member State decides for its own territory. Service providers compile the dossier for this and handle the authorities’ requests for information until the decision.
Where to submit
Via CTIS, the EU portal and database, to all Member States in which you want to run the trial.
Who assesses
Part I jointly under the lead of the reporting Member State, Part II by each Member State on its own.
What the dossier contains
Among other things the protocol, investigator’s brochure, IMPD, GMP evidence, labelling and the national documents listed in Annex I.
Who decides in Germany
The BfArM or the Paul-Ehrlich-Institut, bound by the assessment of the competent ethics committee.
Annex I of the Regulation sets out the full structure of the application dossier. One of the key documents is the Investigational Medicinal Product Dossier (IMPD). It contains information on the quality, manufacture and control of the investigational medicinal product, summaries of non-clinical pharmacology and toxicology, data from previous use in humans and an overall assessment of benefits and risks. Equally central is the Investigator’s Brochure, which presents the clinical and non-clinical data on the investigational medicinal product for the investigators. If an already authorised medicinal product is used within the terms of its marketing authorisation, the summary of product characteristics can replace part of these documents.
When you need this
An application is required for every clinical trial with medicinal products for human use, from first-in-human use to trials with authorised medicinal products. A company’s first application is particularly demanding, because the team is not yet familiar with the requirements of the Regulation and the workflows in CTIS. In addition, there are the national documents for Part II, for example on informed consent, trial sites and insurance.
Work continues after authorisation, because substantial modifications, for example to the protocol or the IMPD, must again be authorised via CTIS. Many sponsors therefore outsource regulatory support for the entire trial.
Legal basis and rules
Regulation (EU) No 536/2014
Governs the authorisation procedure directly in all Member States, including submission and validation (Article 5), assessment of Part I and Part II (Articles 6 and 7), decision (Article 8) and substantial modifications (Chapter III).
Annex I of the Regulation
Defines what an initial application contains, from the cover letter and EU application form through the protocol, investigator’s brochure, GMP evidence and IMPD to insurance, proof of fee payment and data protection.
CTIS
The EU portal and database operated by the European Medicines Agency. Applications, requests for information from the authorities, responses and decisions are handled exclusively through it.
German Medicines Act (Arzneimittelgesetz, AMG), §§ 40 to 42
Governs the German side of the procedure: authorisation by the competent federal higher authority, application in German or English, documents for participants in German, division of tasks between the authority and the ethics committee.
Medical Research Act (Medizinforschungsgesetz)
Amended the AMG with effect from 30 October 2024. Since then, among other things, a deadline of 26 days from validation applies to the assessment under Article 6 if no other Member State is involved, and a Specialised Ethics Committee for special procedures exists at the BfArM.
In Germany, the federal higher authority mainly assesses the aspects of Part I, in particular benefits and risks, while the ethics committee is responsible for Part II and gives its opinion on individual points of Part I. For applications submitted after 30 June 2025, the Specialised Ethics Committee at the BfArM is responsible, among other things, for first-in-human trials of new medicinal products and for advanced therapy medicinal products; otherwise an ethics committee that is competent under the law of the federal state (Land) and registered with the BfArM is responsible.
How the procedure works
The Regulation sets deadlines for each step. The basic procedure under Articles 5 to 8:
01
Submission
You submit the dossier via CTIS to the Member States of your choice and propose one of them as reporting Member State, which confirms its role within six days.
02
Validation
Within ten days the reporting Member State checks whether the trial falls within the scope of the Regulation and whether the dossier is complete. If something is missing, you have a maximum of ten days to provide it; otherwise the application is deemed to have lapsed.
03
Assessment of Part I
The assessment report on Part I is available within 45 days of validation. For requests for information the period can be extended by up to 31 days, and you must respond within the set deadline of no more than twelve days. For advanced therapy medicinal products an extension of 50 days is possible.
04
Assessment of Part II
Each Member State concerned also assesses Part II within 45 days of validation, with the same rules for justified requests for information.
05
Decision
Within five days of the later of the two assessment dates, each Member State notifies whether it authorises the trial, authorises it subject to conditions or refuses it.
Missed response deadlines end the application
If you do not answer the authorities’ requests for information within the set deadline, you lose the application: under Articles 5, 6 and 7 of the Regulation it is then deemed to have lapsed, and for Part I even in all Member States concerned. Before submission, therefore, decide who will answer requests for information.
The authorisation expires in a Member State if no participant has been included in the trial there within two years of notification of the decision, unless you apply for an extension in good time. You must update the investigator’s brochure as soon as new relevant safety information becomes available and review it at least once a year.
What to look for when choosing a provider
A good service provider does not just format documents but anticipates the authorities’ assessment. These questions help when comparing providers:
Questions to ask the provider
How many applications has the provider already submitted via CTIS, and in which Member States acting as reporting Member State has it been involved?
Does it have experience with your type of investigational medicinal product, for example a first-in-human trial, a biologic or an advanced therapy medicinal product?
Can it also review the quality part of the IMPD on a technical level, or does it only handle structure and submission?
How does it ensure that requests for information are answered within the short response deadlines?
Does it know the national requirements for Part II in all countries in which you want to run the trial?
Does it also handle substantial modifications and the extension to further countries after authorisation?
Frequently asked questions
Can I submit Part I only at first?
+
Yes. Under Article 11 of the Regulation you can limit the application to Part I and submit Part II within two years of notification of the conclusion on Part I. If you miss this deadline in a Member State, the application is deemed to have lapsed there.
In which language must the application be submitted in Germany?
+
Under § 40 AMG you can submit the application in German or English. Documents intended for participants or their legal representatives, for example the patient information and the informed consent form, must be available in German.
How do I add another country later?
+
Through a separate application in CTIS under Article 14. The original reporting Member State remains responsible, and the new Member State decides within 52 days of submission, although this period can be extended for requests for information.
Do I need a full IMPD for an authorised comparator?
+
Not necessarily. If it is used within the terms of its marketing authorisation, the summary of product characteristics can replace the non-clinical and clinical data under Annex I. If it is modified, for example for blinding, information on quality is added.
Sources
Every statement in this text was checked against these primary sources (as of 10.11.2026). Laws, guidelines and authority websites, no advertising.
Mikle-Pharm GmbH, based in Landau in der Pfalz, advises pharmaceutical companies on regulatory affairs, marketing authorisation dossiers and project evaluation across the entire medicinal product lifecycle.