Updated on July, 5th 2021
On 29 March 2017 United Kingdom initiated the exit process by written declaration according to Article 50 of the Treaty on the European Union. The transition period during which EU law continues to apply ends at 31 December 2020. According to the current state of the exit negotiations it is expected that there might be a so called “hard Brexit”. In that case after 31 December 2020 the United Kingdom will neither be part of the European Union (EU) nor a State Party to the Agreement on the European Economic Area (EEA) nor apply other transitional arrangements for the variously affected areas. This would also significantly affect clinical trials of medical devices and medicines and other studies with humans.
A clinical trial of a medicinal product or medical device may only be carried out in Germany (and Europe) if and as long as there is a sponsor or a legal representative of the sponsor whose registered place of business is located in a Member State of the EU or in another State Party to the Agreement on the EEA (see § 40 (1) sent. 3 no. 1 AMG, § 20 (1) sent. 3 no. 1a MPG).
In the case of a “hard Brexit”, clinical trials in which the sponsor or legal representative is based in the United Kingdom and where no sponsor or legal representative based in the EU / EEA has been designated until then, must not be continued after the effective date of Brexit. In order to avoid clinical trials and in particular its participants being compromised, it is therefore recommended to nominate a sponsor or legal representative of the sponsor based in the EU or the EEA, timely.
Please also take note to the following aspects: The change of the sponsor or legal representative is a substantial amendment according to § 10 (1) GCP–V and § 22c(3) MPG. This modification may therefore only be implemented after authorization and favorable opinion.
Even though the federal agencies and ethics committees will endeavour for a fast processing, the legal periods of 20 or 30 days for trials with medicinal products and medical devices should be considered. In order to enable processingas quicklyas possiblethemodifications relating to the change of sponsor or legal representative should not be combined with other modifications not directly related to the change of the sponsor or the change of the legal representative. Additional claims concerning the other modifications may significantly delay the processing of the modification due to the change of sponsor or legal representative.
Please note that this change may also affect the validity of the existing insurance for clinical trials and that also the insurancecarrier must be authorized to conduct business within the EU or the EEA.
The change of sponsor or legal representative may also require the policyholder to be corrected in the insurance policy. The change of the sponsor or legal representative or the insurance carrier also requires a corresponding editorial adjustment of the trial protocol and of the informed consent form (as well as other documents and files, if applicable). These documents should be included in the application to § 10 (1) GCP–V or § 23c(2) No. 2 MPG.
On June 28, 2021, the European Commission issued an adequacy decision. Personal data can now flow freely from the European Union to the United Kingdom, where it is subject to a level of protection equivalent in substance to that guaranteed under EU law. It should be noted that the adequacy decision expires four years after its entry into force and can be renewed if the United Kingdom continues to ensure an adequate level of data protection. Pursuant to Art. 13(1)(f) GDPR, data subjects must be informed that the data will be transferred to a third country for which the European Commission has adopted an adequacy decision.
Even though manufacturing and import permits are not part of the assessment of the Ethics Committee, as a precautionary measure, it should be recalled that a “hard Brexit” might have a significant impact in that area, especially in case the import of the IMP into the EU takes place via the United Kingdom or if the medicinal products are manufactured in the United Kingdom. Therefore, appropriate precautions should be taken to ensure uninterrupted availability of the investigational medicinal product in the interest of the trial subjects.
Notification of a substantial Amendment
The submission of an application for a substantial amendment must be done via the DIMDI system in the case of medical device testing. Please update the corresponding information in the notification form (section: sponsor / legal representative). Explain the changes by entering the new sponsor / legal representative and, if applicable, further consequential changes in the notification form and coverletter. If there are changes in the insurance certificate, it must be submitted together with the conditions of insurance.
In case of a clinical trial of a medicinal product, the application for a substantial amendment should generally be submitted to the competent Ethics Committee in a hard copy together with an electronic data medium. Please take into account the information on the website of the responsible ethics committee regarding different submission modalities in the context of the COVID–19 pandemic.The modifications have to be explained, the new sponsor / legal representative and any further consequential changes in the accompanying letter have to be mentioned. The cover letter must be signed by the sponsor or the legal representative based in the EU / EEA. Otherwise, it may be necessary for the authorized representative to prove his authorization in a suitable form (see § 14 (1) VwVfG). If the information in the insurance policy changes, this must be submitted together with the conditions of insurance. Studies that do not fall under the provisions of §§ 40 ff AMG or §§ 20 ff MPG Even in studies that do not fall under the provisions of §§ 40 ff AMG or §§20 ff MPG, there may be consequences in the case of a “hard Brexit”. In particular, the transmission of personal data and samples as well as any existing insurance should be checked accordingly.
|Questions||Remark||Assessment by the ethics committee (EC)|
|Sponsor/legal representative based in the EU/EEA?||accompanying letter (as well as notification form, if applicable)||+|
|Is the insurance valid?||Hand in the renewed insurance certificate and conditions, if applicable||+(the validity of the insurance will be checked in any case)|
|Is the insurance company based in the EU/EEA?||+|
|Informed consent form(s)||Should be handed in with application according to § 10 (1) GCP–V and § 22c (2) no. 2 MPG||It is at the discretion of the EC to review editorially corrected documents in a cursory manner and to provide notes if necessary|
|person responsible for data processing|
|data protection officer of the sponsor / legal representative|
|responsible data protection supervisory authority of the sponsor / legal representative|
|Information about the transfer to a third country|
|Protocol||Current sponsor||Should be handed in with application according to § 10 (1) GCP–V and § 22c (2) no. 2 MPG||It is at the discretion of the EC to review editorially corrected documents in a cursory manner and to provide notes if necessary|
|Is the uninterrupted availability of the investigational medicinal product ensured?||Although, not in the primary area of responsibility of the EC, a lack of medicinal products supply may still lead to withdrawal|