Sponsors Urged To ‘Push Back’ On EU Country-Specific Clinical Trial Requirements
Executive Summary
It has been over five months since the EU Clinical Trial Regulation introduced harmonized requirements for approving new studies. A top European Commission official says that trial sponsors need to keep driving this message home to member states, who are clinging on to their national requirements out of habit.
A senior European Commission official has urged trial sponsors to dig in their heels when faced with disparate requirements being imposed on them by EU member states that are evaluating their applications to conduct studies under the EU Clinical Trial Regulation.
“I would really urge sponsors… to push back” on member state-specific requirements “during the clinical trial authorization phase to give the signal that the submission package [for trial approval and] the way trials are authorized has changed in Europe,” said Kristof Bonnarens, who is team leader at the commission's Directorate-General for Health and Food Safety (DG SANTE).
“There is now a harmonized package that needs to be submitted” to support clinical trial evaluations, Bonnarens said at a virtual webinar organized by the European Medicines Agency on 1 July to discuss the CTR nearly six months after the legislation came into force on 31 January 2022. (Also see "Here At Last: A New Era For Clinical Trials In The EU" - Pink Sheet, 31 Jan, 2022.).
He advised sponsors to make use of the “national contact points” that have been appointed for each member state if they have any questions related to the CTR.
Bonnarens’ remarks were in response to a comment during the webinar by a trial sponsor, who pointed out that as part of the clinical trial application process, some member states were asking for the sub-principal investigator’s CV, but others were not. The sponsor suggested that a common approach was needed on this front across the EU.
To the “question that ‘can we have a single approach?’ my answer is that it is already there,” said Bonnarens. On whether member states should be requiring CVs of sub-principal investigators, the commission representative said: “The answer is, at least in my head, quite straightforward. If it's not in [the] CTR, it does not exist, and specifically [the term] sub-principal investigator – I do not see that word in the CTR” and so the requirement to submit their CVs “does not exist.”
When dealing with any EU regulation, Bonnarens explained that if the legislation “is silent” on certain aspects, then member states can make additional rules, but not in cases where the requirements are clearly defined. In the case of the CTR, he noted, documents needed to support a clinical trial application are defined in Annex 1.
He acknowledged that things may not function in an ideal way in the real world. “If member states require things that are not in that [CTR Annex 1] list… can they do that? Of course, they can,” he noted.
Member states can launch such requirements via the new clinical trial submission portal, the Clinical Trial Information System (CTIS), as the “system itself does not do an intelligence check,” he observed. “But there is… no legal basis to require such things.”
Wet Signatures
Another issue raised at the webinar pertained to some member states insisting on “wet signatures” for certain documents in the trial application.
Bonnarens said there was some “confusion in the [EU regulatory] network on this” topic and clarity was offered via an updated Q&A document published in April. While the CTR does not require signatures, the Q&A document noted that signature requirements for certain documents (eg, site suitability statement) are subject to national law. (Also see "EU Clinical Trial Sponsors Reassured On Member State Dossier Requirements" - Pink Sheet, 14 Apr, 2022.)
If member states ask for signatures, Bonnarens said that this requirement should have a strong legal basis. “It needs to be in the legal text” and should not be the result of a “common habit” that member states have developed over the years, he added.
Making Use Of National Contact Points
Also at the webinar, another trial sponsor said they were frustrated that the ethics committees in some member states “were one step behind national competent authorities” when it came to aligning on CTR requirements and were unable to respond to sponsor queries.
Bonnarens noted that for the commission or anyone else reading the CTR text, the terms “national competent authorities and ethics committees… do not exist.” While ethics committees are only mentioned in the context of being provided with a veto right (in accordance with the national legislation), national competent authorities (NCAs) are not even mentioned in the CTR text except in relation to inspection responsibilities, he said.
NCAs and ethics committees are “old concepts” from the erstwhile Clinical Trial Directive, Bonnarens said, adding that the CTR stops at the member state level. “It’s up to the member states to organize… who is doing what” and execute it via the CTIS, but “there are always teething problems in such major changes,” he said.
He urged sponsors not to contact the ethics committees or the NCAs for CTR-related queries, but to instead make use of the national contact points appointed for each member state. “Those are the people that have the legal mandate to give a member state position” on questions related to the CTR, he added.