Elusive EU Clinical Trial Rules Slip Again – Now To Late 2018

EMA board says it's "critical" that the complex new program provides the "required functionalities to all stakeholders in the most efficient and stable way from the start of its operations."

The schedule for getting the European Union's clinical trial portal and database up and running seems to have slipped again, this time by almost a year compared with earlier estimates. As currently forecast, the new system is not likely to be in place, or the provisions of the new Clinical Trial Regulation (CTR) in effect, until the autumn of 2018.

It's not clear why the new "delivery time frame," which has just been endorsed by the European Medicines Agency's management board and signed off by the executive director, has added another 10 months or so to the late 2017 forecast presented by an EMA official at the TOPRA meeting in Berlin in October.

But it's probably the highly complex nature of the project, and the need to get it right the first time, that is leading the regulator to err on the side of caution when predicting the likely timescale. EMA said that the CTR was an "ambitious project" that involved a "very significant overhaul" of the processes for the oversight and authorization of clinical trials.

The CTR includes a host of new rules in areas such as trial approval procedures, trial results submission and safety reporting, and is expected to streamline the whole clinical trial application system, thereby saving both companies and regulators time, effort and money.

Sponsors will be able to submit a single application to begin a trial, regardless of how many sites or countries are involved. Assessment of the application will be coordinated and a single decision on trial authorization will be taken by each member state. The portal and database will also serve as the central source of information on the lifecycle of all clinical trials conducted in the EU, and will contain other data as well, such as inspection results (Also see "EMA Clinical Trials Portal Training Reflects ‘Big Change Management’ For All" - Pink Sheet, 30 Nov, 2015.).

So it's important that the regulators get it right first time. The additional time frame agreed by EMA's management board will permit the "robust development and testing of the system" and allow "unforeseen difficulties and potential issues" to be resolved, EMA said.

For the board, it is "of critical importance that the EU system provides the required functionalities to all stakeholders in the most efficient and stable way from the start of its operations. This is to ensure delivery of the benefits foreseen by the Clinical Trial Regulation for researchers, patients and the public as a whole."

On the one hand, this may be a frustration for those awaiting the new, streamlined and harmonized rules on EU clinical trial applications and data transparency, but on the other it will give all those involved, particularly EMA, national agencies and industry, more time to prepare for the changes and bring their own systems in line with the new requirements.

New Development Timeline

The portal and database system will be delivered via an iterative approach, with user acceptance testing (UAT) being conducted at each iteration. Those taking part in UAT will include member state experts, sponsor organizations and associations representing users of public information, mainly patient and consumer bodies and health care professional organizations.

Development of the system is being guided by the "functional specifications" agreed in December 2014: it has to be built, tested, audited and declared fully functional before it can get up and running, and only then can the CTR be applied.

While the regulation came into force in June 2014, it stated that its provisions cannot apply before May 28, 2016. This is often cited as the date that the regulation will apply, but in practice it was always a "notional date," being simply two years after the publication of the regulation in the Official Journal of the EU on May 27, 2014.

Earlier predictions suggested mid- or late 2016 for the kick-off, but as time went by this slipped back and 2017 crept into the picture. As recently as October, the timetable presented by the EMA at the TOPRA conference showed an auditable version of the system being released at the end of the third quarter of 2016, with the audit beginning in November 2016 and its findings submitted for endorsement by the EMA management board in March 2017. The system was to be up and running by the end of that year.

But according to the new time frame unveiled by the board Dec. 17, the auditable version of the portal and database system will now not be released until July 2017. The independent audit of the system will begin in August 2017, with completion forecast for November that year and the board expected to endorse the audit in December.

Once the audit is complete and the system has achieved full functionality, the Commission has to publish a notice to this effect in the Official Journal, which is now scheduled for March 2018. The "production version" will go live in September, and the provisions of the CTR will apply from October 2018 "at the latest."

The EMA did say, though, that this was a "maximum time frame" and that "every effort" would be made to bring forward the timing of the audit, and hence application of the regulation. "Such adjustment will be agreed with the EMA management board and communicated by the agency," it added.

There will be a three-year transition period from the date that the regulation applies (that is from October 2018 at the latest). During the first of those three years, clinical trial applications can be made either under the current clinical trials directive (No 2001/20/EC) or under the new regulation. For the following two years, trials authorized under the directive will continue to be governed by that legislation, while any trials authorized under the directive and still under way three years after the regulation applies will then fall under the provisions of the regulation.

[Editor's note: This article is also published in Scrip Regulatory Affairs. "The Pink Sheet" DAILY brings selected complementary coverage from our sister publications to subscribers.]