Vastuskiri

Dear Ruth,

Thank You for Your inquiry. Your questions will be answered below in blue colour:

Question (1): For PMPF studies performed in the Almac USA laboratory, and samples have been collected from Estonian subjects, does Almac need to send a notification to Health Board (Medical Devices Department)?

Question (2): For PMPF studies performed in the Almac NI laboratory, and samples have been collected from Estonian subjects, does Almac need to send a notification to Health Board (Medical Devices Department) in addition to the MHRA?

In case this PMPF involves a device which will be used within the scope of its intended purpose and the study does not involve invasive or burdensome procedures, notification of the Health Board regarding the study is not needed regardless of whether the samples will be analysed in the USA or Northern Ireland of the UK laboratory.

As soon as the device will be used outside the scope of its intended purpose and/or the study involves invasive or burdensome procedures, authorisation of the study by the Health Board is needed.

To assess whether the procedures could be invasive or burdensome, please refer to guidance document MDCG 2021-6 Rev. 1 Regulation (EU) 2017/745 – Questions & Answers regarding clinical investigation.

Question (3) For CDx performance studies, if the left over samples have been collected from Estonian subjects as part of a previous clinical trial which had gained regulatory and ethical approval, and the informed consent provided allowed future studies to be performed on the clinical sample, for testing within the Almac USA laboratory, does Almac need to send a notification to Health Board (Medical Devices Department) or are the previous approvals enough?*

Question (4): For CDx performance studies, if the left over samples have been collected from Estonian subjects as part of a previous clinical trial which had gained regulatory and ethical approval, and the informed consent provided allowed future studies to be performed on the clinical sample, for testing within the Almac NI laboratory does Almac need to send a notification to Health Board (Medical Devices Department) or is the MHRA notification and previous approvals enough?

As per Estonian Medical Devices Act § 211 (3) point 2, the sponsor is required to notify the Health Board of such studies at least 10 days in advance:

(4) The sponsor notifies the Health Board at least ten days in advance if they plan to conduct:

1) an investigation specified in Article 74 of Regulation (EU) 2017/745 of the European Parliament and of the Council, where the investigation would involve submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are not invasive or burdensome;
 2) a performance study specified in subsection 2 of Article 58 of Regulation (EU) 2017/746 of the European Parliament and of the Council involving companion diagnostics using only left-over samples.

This obligation remains in force regardless of whether the samples will be analysed in the USA laboratory or Northern Ireland of the UK laboratory.

Any further details about conducting clinical investigations and performance studies in Estonia could be found in the Medical Devices Act. 

Best regards,

Dear Health Board (Medical Devices Department),

I am writing in regard to queries about performance study notifications as described in IVDR.

From my understanding, there are two occasions when a notification to a Competent Authority is required:

• Post-market performance follow-up (PMPF) study involving a CE marked device being used within its intended use, but for which the study involves additional invasive or burdensome procedures

• Performance studies involving Companion Diagnostics (CDx) using only left-over samples

For context, Almac Diagnostic Services design, develop and manufacture in vitro diagnostic (IVD) devices which are utilised only within Almac’s clinical laboratories in Northern Ireland (NI, UK) and North Carolina (USA). Clinical samples are sent from EU member states to Almac for analysis within the Almac clinical laboratories. The results generated contribute to the clinical performance data for the IVD (for CE marked devices and/or CDx).

If testing is performed in the Almac NI laboratory, a notification will be sent to the UK Competent Authority, the MHRA, to ensure IVDR requirements are met as an EU testing site (as described in the NI Protocol/Windsor agreement). However, we would like to understand additional notification requirements for testing outside the EU (in the USA Almac laboratory) and if additional notifications for testing in NI is required.

Question (1): For PMPF studies performed in the Almac USA laboratory, and samples have been collected from Estonian subjects, does Almac need to send a notification to Health Board (Medical Devices Department)?

Question (2): For PMPF studies performed in the Almac NI laboratory, and samples have been collected from Estonian subjects, does Almac need to send a notification to Health Board (Medical Devices Department) in addition to the MHRA?

Question (3): For CDx performance studies, if the left over samples have been collected from Estonian subjects as part of a previous clinical trial which had gained regulatory and ethical approval, and the informed consent provided allowed future studies to be performed on the clinical sample, for testing within the Almac USA laboratory, does Almac need to send a notification to Health Board (Medical Devices Department) or are the previous approvals enough?

Question (4): For CDx performance studies, if the left over samples have been collected from Estonian subjects as part of a previous clinical trial which had gained regulatory and ethical approval, and the informed consent provided allowed future studies to be performed on the clinical sample, for testing within the Almac NI laboratory does Almac need to send a notification to Health Board (Medical Devices Department) or is the MHRA notification and previous approvals enough?

Kind Regards,

Ruth Scott