Are you a U.S. company contracting with laboratories in Europe to conduct clinical trials on your behalf? This article is for you.
We previously wrote an article on the obligations under European law associated with the conduct of clinical trials and how life sciences companies are required to comply with heavy regulatory requirements, including the General Data Protection Regulation (GDPR), the European Clinical Trial Directive (CTD), and any EU Member State laws implementing any European legislation into national law.
On January 31, 2022, the long awaited EU Clinical Trial Regulation 536/2014 (CTR) came into force, replacing the CTD, with the objective of simplifying and harmonizing the rules that apply to clinical trials in the EU.
What laws apply to clinical trials in the EU?
You may wonder what the difference between a regulation and a directive is. A regulation is a binding legislative act which must be applied in its entirety across the EU whereas a directive only provides a baseline for EU Member States to adopt their own national law implementing the directive. Therefore, the new EU Clinical Trial Regulation is automatically applicable in all EU Member States in its entirety and replaces the new defunct CTD.
To date, companies are required to comply with the GDPR and the CTR to conduct clinical trials in the European Economic Area (EEA). The CTR imposes obligations related to the establishment and conduct of a clinical trial and, in parallel, the GDPR imposes obligations related to the processing of personal data while conducting a clinical trial. To understand how to comply with GDPR in the context of conducting clinical trials, please see here our article on this topic.
What Changes For You?
- Co-ordinate assessment process
Prior to the entry into force of the CTR, clinical trial sponsors had to submit clinical trial applications separately to national competent authorities (NCA) and ethics committees (EC) in each country to gain regulatory approval to run a clinical trial.
While the type of information required for clinical trial applications remains the same with the CTR, the submission process has been refined to co-ordinate and harmonize assessments of multinational applications: a single NCA and EC decision per member state is sufficient. In other words, a coordinated assessment will be led by one reporting member state throughout a trial’s life cycle for multinational applications.
As a sponsor, you can request a desired reporting member state and in case more than one member state is willing to act in such capacity, the member states will decide which one shall function as the reporting state. Regarding the process, the Regulation specifies that the reporting member state has six days from the submission of the application to notify the sponsor and the other member states that it is the reporting member state.
It is therefore very important for sponsors to carefully select their desired reporting Member State and to collaborate with their regulatory teams and Contract Research Organizations (CROs) before submitting an application.
- Clinical Trial Information System (CTIS)
The Regulation leverages a new portal and database called the Clinical Trial Information System (CTIS) where sponsors must upload and submit all data, including initial clinical trial application data and documentation.
This system enables sponsors to apply for clinical trial authorization in up to 30 European countries with a single application which facilitates the expansion of trials to other EEA countries. In addition, it allows national regulators to collaboratively process clinical trial applications in more than one country, request further information, authorize or refuse a trial and oversee an authorized trial. Last but not least, it enables transparency and access to information for any party interested in clinical trials conducted in the EEA.
Under the CTR, sponsors have been authorized to use the CTIS since January 31, 2022 but are not obliged to do so now, as there is a three-year transition period, as follows:
- Until 30 January 2023, clinical trial sponsors may use the CTIS to apply to run a clinical trial under the Clinical Trials Regulation, or they may choose to apply to run a trial under the Clinical Trials Directive;
- From 31 January 2023, clinical trial sponsors will need to use the CTIS to apply to start a new clinical trial in the EU;
- From 31 January 2025, any trials approved under the Clinical Trials Directive that continue running will need to comply with the Clinical Trials Regulation and their sponsors must have recorded information on them in the CTIS.
Therefore, sponsors must have a firm transition strategy in order to comply with the Regulation.
- Public transparency
As previously mentioned, one of the main objectives of the Regulation is to increase public transparency. Until now, transparency generally has not been necessary until the product approval stage.
With the CTR, transparency is required throughout the development process, with some exemptions to protect personal data, commercial confidentiality information, and confidential communication among member states regarding their assessment or clinical trial supervision by member states.
- Consent
In relation to informed consent, the CTR provides additional details on the prior interview with the patient and his/her legally designated representative. Requirements pertain to qualified staff, the type of information given to the patient, the format in which such information is given (taking into account the special needs of the patient), and the requirement to verify if the patient has understood the information. It also requires that a copy of the informed consent be delivered to the patient or his/her representative.
Also of note, the Regulation provides a definition of informed consent as “a subject’s free and voluntary expression of his or her willingness to participate in a particular clinical trial, after having been informed of all aspects of the clinical trial that are relevant to the subject’s decision to participate or, in case of minors and of incapacitated subjects, an authorization or agreement from their legally designated representative to include them in the clinical trial.”
The CTR also provides for the possibility of a simplified informed consent for certain low intervention clinical trials which are conducted in one Member State only and it sets forth the conditions for obtaining informed consent when including the patient in a clinical trial in an emergency situation.
- Deadlines
The CTR implements strict deadlines for responding to application queries or requests for information (RFI): sponsors have 12 calendar days maximum to reply. Additionally, authorizations may expire if no patient is recruited within two years. This is a pure novelty of the CTR. Likewise, the CTR mandates reporting serious breaches within seven days.
The Clinical Trial Regulation introduces significant changes to the previous regulatory framework on clinical trials, encouraging sponsors to think more proactively and frequently about their regulatory strategy.
To learn more about the EU Clinical Trial Regulation (CTR) and about conducting clinical trials in the European Union, contact the Law Office of S. Grynwajc today! Our lawyers are admitted to practice in both the U.S. and the EU, and have particular expertise in advising on the laws and regulations that apply to the healthcare industry.
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This article has been written with the participation of Camille Ley