Issuing authorization for a clinical trial of a medicinal product in Poland and EU – practical tips

Publication date: October 28, 2024

With the current medical standards, the birth of a new medicinal product (drug) can only become a fact as part of a long and expensive research and development process. Such a process is burdened with a high risk of failure. Usually, the research and development process lasts many years and is low in efficiency. However, such research is undoubtedly needed.

How to obtain permission for a clinical trial of a medicinal product?

In order to obtain permission to conduct such a trial in the territory of the Republic of Poland, an application for permission must first be submitted. Such an application may be submitted only by the sponsor – which stands for a natural person, company, institution or organization responsible for initiating, managing and arranging the financing of a clinical trial (Article 2, paragraph 2, point 14 of the Regulation of the European Parliament and of the Council (EU) No 536/2014 of 16 April 2014, OJ EU.L.2014.158.1). The sponsor is obliged to submit such an application via CTIS (i.e. the new European system, Clinical Trials Information System) to each interested Member State concerned by a given clinical trial. In the case of the Republic of Poland, the body that issues permits for clinical trials is the President of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.

CTIS Account

In accordance with the CTR (Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 repealing Directive 2001/20/EC (OJ EU. L. of 2014, No. 158, p. 1, as amended), applications for authorization to conduct clinical trials can only be submitted via the new European CTIS system, so it is advisable to set up an account in this system. The user of this system can be the sponsor, an authorized employee or collaborator of the sponsor. In order to gain access to the sponsor’s panel in CTIS, the user must have a European Medicines Agency (EMA) account. If they have previously created an account in one of the other EMA applications (e.g. Eudralink, SPOR, IRIS, EudraVigilance, OMS), they can use the same EMA account to also have access to the sponsor’s panel in CTIS. However, if the user does not have any EMA account, it is necessary to create an account by self-registering on the EMA account management page. There are several options for registering in CTIS and depending on which the sponsor chooses, it may also be necessary to establish and assign users the appropriate access roles allowing them to submit an application for permission to conduct a study on behalf of the sponsor (authorized employees and collaborators of the sponsor).

The European Medicines Agency recommends that sponsors carefully read the CTIS training modules and the CTIS Sponsor Manual, which provides detailed information on using the European Clinical Trials Programme, before creating an account and submitting an application.

Organization registration

Before submitting an application, the sponsor must be certain that their organization is registered in the EU Organisation Management Service (OMS). This is a necessary condition for submitting an application for permission to start clinical trials. A sponsor who does not have their organization registered in OMS must be aware that the registration process, according to official guidelines, takes from 5 to 10 days.

Registration of a medicinal product

Before submitting an application for authorisation to conduct a clinical trial, the sponsor must not forget to register (or ensure that they have registered) the details of all medicinal products that will be used in the clinical trial in eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD). The XEVMPD database should contain data on all medicinal products authorized for marketing in the EEA or under development (including the clinical trial stage). However, there is no need to register the so-called placebo in the database XEVMP.

Documentation and data required to submit an application

Submitting an application in the CTIS system is carried out in three parts: the preliminary part, part I and part II.

Introductory part

At this stage of submitting an application in the system, you should provide the simplest, most basic information about the planned clinical trial. First of all, it is about:

• name of the study and study sponsor (selected from the OMS list).

You will also need documents such as:

• cover letter from letter B of Annex I to CTR
• confirmation of payment of the fee (Details regarding the liability to the fee and its amount in the Republic of Poland are specified in Art. 58 of the Clinical Trials Act.)
• declaration of compliance with GDPR requirements.

In this section you should also list any interested Member States and propose which one will be the reporting Member State. When selecting Member States, you should also indicate how many participants from each country are expected to take part in the study.

Part I

At this stage, you should provide more detailed information:

• Phase of the planned study
• Type of disease that the study is about
• Therapeutic area
• Scope and purpose of the clinical trial
• Study inclusion and exclusion criteria
• Study endpoints
• Duration of a clinical trial from the beginning of study recruitment to its completion
• Data on recruited study participants (age range, gender, whether they are healthy or have any diseases).

You should also not forget about the documents at this stage:

• Test protocol in accordance with letter D of Annex I to the CTR
• Investigator’s brochure in accordance with letter E of Annex I to the CTR
• Good Manufacturing Practice Documentation in relation to the investigational medicinal product in accordance with letter F of Annex I to the CTR
• Auxiliary medicinal product dossier in accordance with point G of Annex I to the CTR
• Scientific indications and paediatric investigation plan in accordance with point I of Annex I to the CTR (if applicable)
• The content of the labelling of the investigational medicinal product in accordance with Annex VI to the CTR

Part II

As part of this stage, data regarding the practice of conducting the planned clinical trial should be provided. First of all, such as:

• Identification of clinical trial sites and investigators for each Member State concerned by the study.

Of course, as in the previous stages, one cannot forget about the documents (separately for each Member State concerned):

• Clinical trial recruitment rules in accordance with letter K of Annex I to the CTR
• Information for study participants
• Informed consent form and informed consent procedure according to letter L of Annex I to the CTR
• Documents confirming the appropriate qualifications of the researcher in accordance with letter M of Annex I to the CTR
• Documents confirming the appropriate quality of selected clinical research centers in accordance with letter N of Annex I to the CTR
• Evidence of insurance or membership of a national compensation mechanism in accordance with the national law of the Member State concerned in accordance with point O of Annex I to the CTR
• Documents relating to the financing of the clinical trial in accordance with letter P of Annex I to the CTR
• Documents relating to compliance with personal data protection rules in the Member State pursuant to letter R of Annex I to the CTR
• Documents confirming compliance with the rules regarding the collection of biological samples from participants and the storage and future use of these samples.

Language of submitted documentation

Article 10 of the Clinical Trials Act contains detailed requirements regarding the language in which the documentation described above should be submitted. According to this article, most of the documents attached under Stage I may be prepared in English or Polish, while the vast majority of documents submitted under Part II must be prepared in Polish.

Sponsor’s choice regarding application submission method

The sponsor may submit a full application, which will consist of both Part I and Part II simultaneously to all Member States concerned. It may also submit a partial application: Part I to all Member States concerned and Part II not to any Member State or only to some Member States.

Rapporteur’s role and evaluation of the application by the Member States

In the initial part of the application, the sponsor is required to propose which of the selected Member States concerned should act as the reporting Member State. This proposal is not binding – this means that the Member States concerned may, by agreement, select another Member State as the reporting Member State. In the event that the Member States cannot reach an agreement on the selection of the reporting Member State, the reporting Member State is the one proposed by the sponsor. However, if the clinical trial concerns only one Member State, this Member State becomes the reporting Member State. Once the reporting Member State has been determined, the Member States proceed to the assessment of the application, which takes place in three main stages: the formal assessment of the application, the assessment of Part I of the application, the assessment of Part II of the application.

Validation, i.e. the stage of formal assessment of the application

Within 10 days of submission of the application, the reporting Member State shall validate the application:

• It takes into account the comments submitted by other interested Member States
• Provides the sponsor with information via CTIS whether the clinical trial applied for falls within the scope of the CTR
• Checks whether the application documentation is complete in accordance with Annex I of the CTR.

Where the reporting Member State has not provided the sponsor with information within the abovementioned deadline, the clinical trial applied for shall be deemed to be covered by the CTR and the application dossier shall be deemed to be complete.

Where the reporting Member State determines that the application dossier is incomplete or that the clinical trial applied for is not covered by the CTR, it shall inform the sponsor thereof via the CTIS and set a deadline of no more than 10 days for the sponsor to submit comments on the application or to complete the application dossier in the CTIS.

Within 5 days of receipt of comments on the application or the completed application dossier, the reporting state shall notify the sponsor whether the application complies with the CTR requirements. If the sponsor fails to complete the application within the specified deadline, the application shall be deemed to have lapsed in all Member States concerned.

Application Part I Assessment Stage

At this stage, the rapporteur assesses the application from the following perspectives:

• Whether the clinical trial is low-intervention, if so defined by the sponsor;
• Compliance with Chapter V of the CTR with respect to:

– anticipated therapeutic and public health benefits

– risks and inconveniences for the participant

• Compliance with the requirements for the manufacture and import of investigational medicinal products and auxiliary medicinal products specified in Chapter IX of the CTR
• Compliance with the labelling requirements specified in Chapter X of the CTR
• Completeness and Adequacy of the Researcher’s Brochure.

Once the above-mentioned aspects have passed verification, the rapporteur draws up an evaluation report which contains one of the following conclusions:

• The study is permissible according to the CTR
• The study is permissible according to the CTR, after meeting the additional requirements listed in the conclusion
• Conducting the study is not permissible according to the CTR.

Within 45 days of the end of the formal assessment phase of the application (validation date), the rapporteur shall submit the final version of Part I of the assessment report to the sponsor via CTIS. If the rapporteur Member State wishes to consult experts, it may extend this period by a further 50 days for clinical trials concerning advanced therapy investigational medicinal products or medicinal products as defined in point 1 of the Annex to Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.

In the period between the validation date and the reporting date, the rapporteur may request additional information from the sponsor (CTIS). The sponsor must provide the requested information within the deadline specified by the rapporteur. This deadline may not exceed 12 days from receipt of the request. In order to obtain and assess additional information from the sponsor, the Member State may extend the deadline by a maximum of a further 31 days.

Application Part II Assessment Stage

The evaluation of Part II of the application differs in that it is not performed by the rapporteur but by each Member State concerned separately. The Member States shall evaluate the application in relation to the aspects set out in Article 7(1) of the CTR, in particular:

• compliance of the rules for remunerating or providing compensation to trial participants with the requirements set out in Chapter V of the CTR
• whether researchers have appropriate qualifications in accordance with national law
• whether the facilities where the research is to be carried out are suitable for conducting the research in accordance with the CTR requirements

Each Member State concerned shall assess Part II of the application within 45 days of the validation date (the date of the end of the formal assessment phase) and shall submit Part II of the assessment report to the sponsor via CTIS. The assessing Member States may also request additional information from the sponsor (CTIS). The sponsor shall provide additional information via CTIS within the time period specified by the Member State, which shall not exceed 12 days. Upon receipt of the additional information, the Member State concerned shall assess it within a time period not exceeding 19 days.

Member States Decision on Clinical Trial

Each Member State concerned shall notify the sponsor through CTIS whether it:

• issues a permit for a clinical trial
• issues a permit under certain conditions
• refuses to issue a permit.

Notification shall be made by means of a single decision within 5 days from the date of submission of Part I of the assessment report or from the last day of the assessment of Part II of the application, whichever is later. As a rule, Part I of the assessment report prepared by the rapporteur Member State is binding on the other Member States. A non-rapporteur Member State may only challenge a positive conclusion of the rapporteur Member State as regards Part I of the report on the following grounds:

• if that Member State considers that participation in the clinical trial would result in the subject receiving worse treatment than that which is standard clinical practice in the Member State concerned
• the clinical trial is to use medicinal products whose use is prohibited or restricted under national law (Article 90 of the CTR)
• additional considerations regarding participant safety and data robustness and reliability raised in the Part I evaluation.

Refusal to issue a permit

Where a Member State disagrees with the conclusion regarding Part I, it shall communicate its disagreement, together with a detailed justification, to the Commission, all Member States and the sponsor through CTIS.

A Member State concerned may refuse to authorise a clinical trial if it disagrees with the conclusion of the reporting Member State as regards Part I of the assessment report or if it finds, on duly justified grounds, that the aspects addressed in Part II of the assessment report are not complied with or where an ethics committee has issued a negative opinion. Each Member State must put in place an appeal procedure in the event of such a refusal.

If the Member State concerned has not notified the sponsor of its decision within the period referred to above (5 days from the date of submission of Part I of the assessment report or from the last day of the assessment of Part II of the application, whichever is the later), the conclusion on Part I of the assessment report shall be deemed to be the decision of the Member State concerned on the application for authorisation of the clinical trial.

Permission for clinical trials in Poland

In the case of the Republic of Poland, the provisions of the Act of 14 June 1960 – the Code of Administrative Procedure – shall apply to the procedure for issuing a permit for a clinical trial, and in the event of a negative decision of the ethics committee – Art. 34 of the Code of Administrative Procedure.

Withdrawal of application by sponsor

The sponsor has the right to withdraw its application at any time up to the reporting date. If the application is withdrawn before the sponsor is notified of the conclusion on Part I of the assessment report, the withdrawal of the application applies to the entire application in all Member States concerned. After the withdrawal, the application may be resubmitted. Such resubmitted application shall be considered as a new application for authorisation of another clinical trial.

Sponsors Be Cautious

Sponsors must also be careful about the specific regulation contained in Article 8(9) of the CTR: if no subject has been included in a clinical trial in a Member State concerned within 2 years from the date of notification of the authorisation, the authorisation shall expire in that Member State concerned, unless, at the sponsor’s request, this period has been extended in accordance with the procedure set out in Chapter III of the CTR.