2. General Questions

2.1 Name of Regulatory Authority

The Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (“the Office”/URPL).

2.2 Name of Ethics Committee

The Act provides for a new structure for the functioning of bioethics committees evaluating clinical trials. It established the Supreme Bioethics Committee (Naczelna Komisja Bioetyczna “NKB”), operating at the Medical Research Agency. 

The NKB is responsible for supervising the ethical assessment of clinical research and organizing the work of the bioethics committees included in the official list of bioethics committees. The NKB and bioethics committees are responsible for the ethical assessment of a clinical trial taking place in Poland.

The NKB published the list of the Polish bioethics committees which are authorized to carry out evaluation of a clinical trial of a medicinal product.

The list of Bioethics Committees in Poland authorized to carry out ethical review of a clinical trial of a medicinal product is published in the Supreme Bioethics Committee.

2.3 Clinical Trial Application Language

Predominantly in Polish – but see below: some parts may be in English.

Article 10 (1) of the Act of March 09, 2023, on Clinical Trials of Medicinal Products for Human Use, indicates the language accepted for each of the documents: 

(1) Annex I to Regulation (EU) 536/2014:

(a) the documentation listed in Parts B-I and Q and R is prepared in English or Polish, except for the summary of the clinical trial protocol, which is prepared in Polish,

(b) the dossier referred to in J-P is prepared in Polish,

(c) the application listed in Part C shall be supplemented with translations in Polish in the sections where the system allows for the introduction of such translation,

(d) documents confirming the appropriate suitability of the clinical trial sites listed in Part N are presented as signed and dated copies of documents.

(2) Annex II to Regulation (EU) 536/2014:

(a) the documentation listed in Parts B, C, F, and G is prepared in English or Polish, except for the summary of the clinical trial protocol, which is prepared in Polish,

(b) the documentation listed in Parts D and E is prepared in the language in which the original application for the authorization of the clinical trial was submitted,

(c) the application listed in Part C shall be supplemented with translations in Polish in the sections in which the system allows for such a translation to be introduced.

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes. A single application submission for Part I (intended for URPL review) and Part II (intended for EC review) can be submitted in parallel through the EMA CTIS portal.

Article 11 of the Act

“A clinical trial may be commenced after obtaining a decision on the issuance of a clinical trial permit, taking into account Article 8 (6) and Article 14 (11) of Regulation 536/2014.”

Further, Art 4, EU CTR 536/2014 provides that: 

“A clinical trial shall be subject to scientific and ethical review and shall be authorized in accordance with this Regulation.

The ethical review shall be performed by an ethics committee in accordance with the law of the Member State concerned. The review by the ethics committee may encompass aspects addressed in Part I of the assessment report for the authorization of a clinical trial as referred to in Article 6 and in Part II of that assessment report as referred to in Article 7 as appropriate for each Member State concerned.”

2.5 Can regulatory authority and EC submission be done in parallel?

Yes, a single, centralized, EU application is made, with the application being processed according to EU CTR 536/2014.

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

If the product is being imported from outside the EEA, then the Office President’s certificate attesting that the clinical trial has been entered in the Central Register of Clinical Trials is required. If importation is from within the EEA, then no such certification is required.            

According to Art 37K (4) of the Pharmaceutical Law of 2001 (consolidated text 07 Oct 2022):

“(3) Import of investigational medicinal products and equipment necessary for conducting clinical trials shall require the Office President’s certificate attesting that the clinical trial has been entered in the Central Register of Clinical Trials and that the product or equipment concerned is imported for the purposes of such trial.

(4) The provision of paragraph 3 shall not concern the import of investigational medicinal products and equipment necessary for conducting clinical trials from a European Union Member State or a European Free Trade Association (EFTA) Member State – party to the Agreement on the European Economic Area.” 

More information and forms can be found on the Polish government page.

2.7 Biological Specimen Export Requirements

We have not been able to determine an answer to this question.

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes, subject to the applicable rules.

The inclusion of GMOs is contemplated by Clinical Trial Regulation (EU) 536/2014 which provides that the covering letter to the EMA, submitting an application to carry out a clinical study, must state whether the investigational medicinal product consists of or contains a GMO - see Annex I.B(f).

2.9 Is in-country sponsor presence/representation required?

If the Sponsor is not established in the EU, the Sponsor needs to establish a legal representative within the EU. 

See: Art 74, EU CTR 536/2014: 

“1. Where the sponsor of a clinical trial is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication to that legal representative shall be deemed to be a communication to the sponsor.

2. Member States may choose not to apply paragraph 1 as regards clinical trials to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical trial who shall be the addressee for all communications with the sponsor provided for in this Regulation.

 3. As regards clinical trials to be conducted in more than one Member State, all those Member States may choose not to apply paragraph 1 provided that they ensure that the sponsor establishes at least a contact person in the Union in respect of that clinical trial who shall be the addressee for all communications with the sponsor provided for in this Regulation.”

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

Yes, a local investigator is required under Article 2 of the Act of March 2023 on Clinical Trials of Medicinal Products for Human Use. 

Art 49 of the EU CTR 536/2014 also provides that:

“The investigator shall be a medical doctor as defined in national law, or a person following a profession which is recognized in the Member State concerned as qualifying for an investigator because of the necessary scientific knowledge and experience in patient care. Other individuals involved in conducting a clinical trial shall be suitably qualified by education, training, and experience to perform their tasks”.

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

No, under the EU Clinical Trial Regulation 536/2014, there is no role for a Chief or Coordinating Investigator, only for a Principal Investigator and Investigator.

Article 73, EU CTR 536/2014, indicates:

“A principal investigator shall ensure compliance of a clinical trial at a clinical trial site with the requirements of this Regulation. The principal investigator shall assign tasks among the members of the team of investigators in a way which is not compromising the safety of subjects and the reliability and robustness of the data generated in the clinical trial at that clinical trial site”.

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled?

Yes, a written contract is required between the sponsor and the CRO, delegating authority. The contract does not need to be notarized and/or apostilled, so far as we are aware, at an EMA level, now that applications are made electronically.

Article 71, EU CTR 536/2014, provides clarification on the sponsor's role:

“Sponsor

A clinical trial may have one or several sponsors.

Any sponsor may delegate, in a written contract, any or all of its tasks to an individual, a company, an institution, or an organization. Such delegation shall be without prejudice to the responsibility of the sponsor, in particular regarding the safety of subjects and the reliability and robustness of the data generated in the clinical trial. The investigator and the sponsor may be the same person.”

However, for contract negotiations at a site level, it may be requested to the Sponsor and/or CRO a “power of attorney” for those individuals authorized to sign the contracts. Additionally, a document confirming the registration of the Sponsor/CRO to the Polish registry companies will be requested. Signatory rights of the person signing PoA on behalf of the Sponsor/EU Representative are clearly documented in the extract from the commercial register of the entity they represent (it has to be clear if this person(s) can sign individually or jointly with another company representative). In case this is not clear from the commercial register, then a notary statement with this confirmation must be provided.

2.13 Is there a requirement to register clinical trials on a local registry or database?

No, the current Act-March 2023 does not indicate that clinical trials must be registered in a local registry.         

However, there are local registries available, the list of those registries can be found within the Patient portal under the Medical Research Agency. 

Additionally, as of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS. EU CTR continues to display information on EudraCT trials. EudraCT remains available for amendments to EudraCT trials, creation of PIP/Art 46 third country files (see FAQs), updating of EudraCT trials’ statuses, and relevant submission of results.

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

25 years from the end of the clinical trial. 

See Article 58, EU CTR 516/2014

“Archiving of the clinical trial master file

Unless other Union law requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least 25 years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national law.

The content of the clinical trial master file shall be archived in a way that ensures that it is readily available and accessible, upon request, to the competent authorities.

Any transfer of ownership of the content of the clinical trial master file shall be documented. The new owner shall assume the responsibilities set out in this Article.

The sponsor shall appoint individuals within its organization to be responsible for archives. Access to archives shall be restricted to those individuals.

The media used to archive the content of the clinical trial master file shall be such that the content remains complete and legible throughout the period referred to in the first paragraph.

Any alteration to the content of the clinical trial master file shall be traceable.”

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

Relevant provisions on periodic safety reporting are a part of the EU CTR.

Articles 41 & 42, EU CTR 536/2014, relate to this.  

Art 41 CTR: “Reporting of adverse events and serious adverse events by the investigator to the sponsor

1. The investigator shall record and document adverse events or laboratory abnormalities identified in the protocol as critical to the safety evaluation and report them to the sponsor in accordance with the reporting requirements and within the periods specified in the protocol.

2. The investigator shall record and document all adverse events, unless the protocol provides differently. The investigator shall report to the sponsor all serious adverse events occurring to subjects treated by him or her in the clinical trial, unless the protocol provides differently.

The investigator shall report serious adverse events to the sponsor without undue delay but not later than within 24 hours of obtaining knowledge of the events, unless, for certain serious adverse events, the protocol provides that no immediate reporting is required. Where relevant, the investigator shall send a follow-up report to the sponsor to allow the sponsor to assess whether the serious adverse event has an impact on the benefit-risk balance of the clinical trial...”

Art 42 CTR: “Reporting of suspected unexpected serious adverse reactions by the sponsor to the Agency

1. The sponsor of a clinical trial performed in at least one Member State shall report electronically and without delay to the database referred to in Article 40(1) all relevant information about the following suspected unexpected serious adverse reactions:

(a) all suspected unexpected serious adverse reactions to investigational medicinal products occurring in that clinical trial, irrespective of whether the suspected unexpected serious adverse reaction has occurred at a clinical trial site in the Union or in a third country;

(b) all suspected unexpected serious adverse reactions related to the same active substance, regardless of pharmaceutical form and strength or indication investigated, in investigational medicinal products used in the clinical trial, occurring in a clinical trial performed exclusively in a third country, if that clinical trial is sponsored:

(i) by that sponsor, or

(ii) by another sponsor who is either part of the same parent company as the sponsor of the clinical trial, or who develops a medicinal product jointly, on the basis of a formal agreement, with the sponsor of the clinical trial. For this purpose, provision of the investigational medicinal product or information to a future potential marketing authorization holder on safety matters shall not be considered a joint development; and

(c) all suspected unexpected serious adverse reactions to investigational medicinal products occurring in any of the subjects of the clinical trial, which are identified by or come to the attention of the sponsor after the end of the clinical trial.

2. The period for the reporting of suspected unexpected serious adverse reactions by the sponsor to the Agency shall take account of the seriousness of the reaction and shall be as follows:

(a) in the case of fatal or life-threatening suspected unexpected serious adverse reactions, as soon as possible and in any event not later than seven days after the sponsor became aware of the reaction;

(b) in the case of non-fatal or non-life-threatening suspected unexpected serious adverse reactions, not later than 15 days after the sponsor became aware of the reaction;

(c) in the case of a suspected unexpected serious adverse reaction which was initially considered to be non-fatal or non-life threatening but which turns out to be fatal or life-threatening, as soon as possible and in any event not later than seven days after the sponsor became aware of the reaction being fatal or life-threatening….”.

Additionally, a clarification on safety reporting was posted on the URPL website on 15 May 2023, providing the following clarification on the safety reporting requirements for studies submitted according to the EU CTR 536/2014:

“…For studies submitted in accordance with the provisions of Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC (OJ 2014/2014 EU L 158, 27.05.2014, p. 1, as amended. (as amended), hereinafter referred to as 'Regulation 536/2014' – and therefore via the CTIS portal – annual patient safety reports and reports of unexpected serious adverse reactions to medicinal products must be submitted in accordance with that Regulation, i.e. Annual Participant Safety Reports (ASRs) to the ASR EudraVigilance Module on the CTIS Portal and reports of Unexpected Serious Adverse Reactions (SUSARs) directly to the EudraVigilance Clinical Trial Module. With regard to studies carried out in accordance with Regulation 536/2014, it is not required to submit safety reports directly to the President of the Office (URPL).”

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)? 

Annual reports of clinical trials falling within the scope of the EU CTR 536/2014 shall be submitted to the EMA Clinical Trials Information System (CTIS).

Article 43, EU CTR 536/2014:

“1. Regarding investigational medicinal products other than placebo, the sponsor shall submit annually through the database referred to in Article 40(1) to the Agency a report on the safety of each investigational medicinal product used in a clinical trial for which it is the sponsor.

2. In the case of a clinical trial involving the use of more than one investigational medicinal product, the sponsor may, if provided for in the protocol, submit a single safety report on all investigational medicinal products used in that clinical trial.

3. The annual report referred to in paragraph 1 shall only contain aggregate and anonymized data.

4. The obligation referred to in paragraph 1 starts with the first authorization of a clinical trial in accordance with this Regulation. It ends with the end of the last clinical trial conducted by the sponsor with the investigational medicinal product…”.

There are also other reporting/notification requirements, that will be required to be performed within the CTIS, those are:

2.17 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol? 

Yes, notification is required within seven days of becoming aware of the breach (see details below).    

Notification of a Serious Breach allows the sponsor to inform about a breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial. These notifications must be made without undue delay but no later than 7 days from the date on which the sponsor became aware of the breach (article 52 of the CT Regulation). 

For more information, refer to the following EMA guidance on notification of serious breaches: 

1. Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol 
2. Appendix III b – Information to be submitted with a notification of a serious breach

2.18 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

Yes – Art 40(1) of the Act of March 2023 provides that: 

“Article 40

(1) The sponsor and the investigator by virtue of conducting a clinical trial shall be subject to compulsory liability insurance for damages caused in connection with the conduct of the clinical trial.

(2) In the case of a low-intervention clinical trial within the meaning of Article 2 (2) (3) of Regulation 536/2014, the sponsor shall not be required to take out liability insurance for damages caused in connection with the conduct of the clinical trial.

(3) The sponsor shall attach to the application for a clinical trial permit proof of insurance confirming the conclusion of the liability insurance contract referred to in paragraph (1) and payment of the deposit referred to in Article 42 (1).

(4) The civil liability insurance referred to in paragraph (1) shall cover the civil liability of the investigator and the sponsor for damage consisting in bodily injury, disorder of health, or death of the clinical trial participant, during the period of insurance coverage, caused in connection with the conduct of the clinical trial.

(5) The liability insurance referred to in paragraph (1) shall not cover damages:

1) consisting of damage, destruction, or loss of property;

2) resulting from the development of addiction in a clinical trial participant, if the possibility of development of addiction was presented in writing to the clinical trial participant at the start of the clinical trial;

3) directly or indirectly caused by or related to asbestos;

4) involving an obligation to pay contractual penalties;

5) arising from acts of war, martial law, riot and civil commotion, as well as acts of terror.

(6) The liability insurance referred to in paragraph (1) shall cover all damages within the scope referred to in paragraph (4), subject to paragraph (5), without the possibility of contractual limitation by the insurance company of the payment of damages.

(7) The obligation of liability insurance referred to in paragraph (1) shall arise no later than the date of submission of the application for a clinical trial permit.

(8) The minimum guarantee amount of the liability insurance referred to in paragraph 1 with respect to one event and all events, the consequences of which are covered by the contract of liability insurance for damage caused in connection with the conduct of a clinical trial, depends on the number of participants in the clinical trial and is equivalent in zlotys to:

1) up to 50 people - 2,000,000 euros;

2) above 50 persons - 5,000,000 euros.

(9) The minimum guarantee amount referred to in paragraph (8) is determined jointly with respect to the sponsor and all investigators participating in the clinical trial in question.

(10) The amounts referred to in paragraph 8 shall be calculated using the average euro exchange rate announced by the National Bank of Poland for the first time in the year in which the insurance contract was concluded as referred in paragraph 1."