Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

My company is doing a Clinical Study in Europe (France, Germany and UK [previously part of EU]). The regulatory & clinical team which did the original CTN submission are not with the company and there is poor documentation, so I am not sure what was submitted. I need some guidance/education regarding Clinical Trial Notifications (CTN) in Europe:

1. For starting a clinical study in Europe, do we need to submit our clinical study protocol and other documents to Ethics Committee and to the Competent Authority (CA) in the country where we intend to do the study?
2. If we make any protocol changes, do we need to notify/get prior approval from the CA of the respective countries where we are doing the clinical study?
3. What are the requirements (if someone can point me to them) which triggers a submission/notification to the CA? Eg. If we are making a minor change instead of a change to I/E criteria, would that need a submission/notification to the CA?
4. Will the Notified Body review the submission approvals or notification confirmation while doing an audit?

Well, first of all, it is complicated. Currently, clinical trial applications are unique to each country's CA, but the fundamental requirement is for an IMPD, IB and protocol. And, yes, both CA and ICE submissions are required. And, there are guidelines on what is considered a major vs. minor amendments that do or do not require CA and ICE prior approvals.

However, note that as of January 31, the new clinical trial regulation (CTR) is going live and central applications will be possible and eventually required. There is not enough space here to go into details on the benefits and potential painful points, but most people are happy to see these changes come. I suggest that you find a resource to get you quickly up to speed on it. I have seen some very good communications come thru DIA on this topic.

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Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States
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Original Message:
Sent: 09-Dec-2021 03:37
From: Anonymous Member
Subject: Clinical Trial Notifications (CTN) in Europe

This message was posted by a user wishing to remain anonymous

My company is doing a Clinical Study in Europe (France, Germany and UK [previously part of EU]). The regulatory & clinical team which did the original CTN submission are not with the company and there is poor documentation, so I am not sure what was submitted. I need some guidance/education regarding Clinical Trial Notifications (CTN) in Europe:

1. For starting a clinical study in Europe, do we need to submit our clinical study protocol and other documents to Ethics Committee and to the Competent Authority (CA) in the country where we intend to do the study?
2. If we make any protocol changes, do we need to notify/get prior approval from the CA of the respective countries where we are doing the clinical study?
3. What are the requirements (if someone can point me to them) which triggers a submission/notification to the CA? Eg. If we are making a minor change instead of a change to I/E criteria, would that need a submission/notification to the CA?
4. Will the Notified Body review the submission approvals or notification confirmation while doing an audit?

Based on the mention of a Notified Body, I presume the original poster is discussing a medical device (though it wasn't said explicitly). In that case, the EU MDR clinical investigation articles will apply (see Chapter VI starting at Article 61), though each country's CA will apply their own procedures (e.g. ANSM for France, BfArM for Germany). The UK will follow their own (2002) Medical Device Regulation, which is a transposition of the EU MDD which was in effect at the time of Brexit (MHRA is their device CA).

To address (at least some of) your questions:
1. Yes, EC & CA approvals are generally necessary in European countries before starting a clinical study for an investigational device (i.e. not yet CE-marked). Each country has their own procedures and, recently, the UK is implementing a single 'streamlined' approach for both that should simplify the process (for both drugs and devices, I believe it is set to become mandatory in the new year).
2. The need to notify CAs after initial approval for the study depends on the type of change - see MDR Article 75.
3. See above.
4. I am not sure if a NB will review this as it is not in their remit (the responsibility belongs to the respective CAs) however they will review the CER which will include outcome from the clinical studies.

------------------------------
Jonathan Amaya-Hodges
Sr. Principal Consultant
jamaya-hodges@suttonscreek.com
Suttons Creek, Inc.
United States
https://suttonscreek.com/
------------------------------

Original Message:
Sent: 09-Dec-2021 15:51
From: Glen Park
Subject: Clinical Trial Notifications (CTN) in Europe

Well, first of all, it is complicated. Currently, clinical trial applications are unique to each country's CA, but the fundamental requirement is for an IMPD, IB and protocol. And, yes, both CA and ICE submissions are required. And, there are guidelines on what is considered a major vs. minor amendments that do or do not require CA and ICE prior approvals.

However, note that as of January 31, the new clinical trial regulation (CTR) is going live and central applications will be possible and eventually required. There is not enough space here to go into details on the benefits and potential painful points, but most people are happy to see these changes come. I suggest that you find a resource to get you quickly up to speed on it. I have seen some very good communications come thru DIA on this topic.

------------------------------
Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States

Original Message:
Sent: 09-Dec-2021 03:37
From: Anonymous Member
Subject: Clinical Trial Notifications (CTN) in Europe

This message was posted by a user wishing to remain anonymous

My company is doing a Clinical Study in Europe (France, Germany and UK [previously part of EU]). The regulatory & clinical team which did the original CTN submission are not with the company and there is poor documentation, so I am not sure what was submitted. I need some guidance/education regarding Clinical Trial Notifications (CTN) in Europe:

1. For starting a clinical study in Europe, do we need to submit our clinical study protocol and other documents to Ethics Committee and to the Competent Authority (CA) in the country where we intend to do the study?
2. If we make any protocol changes, do we need to notify/get prior approval from the CA of the respective countries where we are doing the clinical study?
3. What are the requirements (if someone can point me to them) which triggers a submission/notification to the CA? Eg. If we are making a minor change instead of a change to I/E criteria, would that need a submission/notification to the CA?
4. Will the Notified Body review the submission approvals or notification confirmation while doing an audit?