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The new EU clinical trial regulation: a regulatory affairs perspective

13 March 2015


Why is it necessary?
The new regulation will replace the controversial and much criticised EU directive (Directive 2001/20/EC). The existing directive was introduced with the intention of harmonising and simplifying clinical trials in the EU. However, in practice the directive is ostensibly antithetical to the objectives for which it was designed, evidenced by a 90% rise in the delays for launching a clinical trial, a 2-fold increase in administrative costs for non-commercial trials and, rather alarmingly, a 25% fall in the number of clinical trials conducted in Europe between 2007 and 20112.
How did this directive achieve the opposite of what it was designed to do? One reason may lie in the fact it was introduced as a directive rather than a regulation. Under the process known as ‘transposition’ the directive sets the framework but the practical details of implementation are left for the member states to decide individually. Therefore, multiple applications of nearly identical dossiers have to be made in each member state concerned, which leads to multiple assessments and, inevitably, divergent decisions, timelines and outcomes. The overbearing bureaucracy which has stifled the speed of progress leaves applicants feeling strangled by red tape.

The new regulation
The new EU clinical trial regulation was published in the Official Journal of the European Community on the 27th May 2014 (Regulation (EU) No 536/2014). A regulation, unlike a directive, will be directly applicable in all EU member states without the need for national interpretations and legislation3.
The regulation will enable clinical trial sponsors to submit a single application, via a centralised portal, for all EU countries in which they would like to conduct their trial. The applicant will propose a reporting member state (RMS), however; if another MS offers to lead the assessment within 3 days then the proposed RMS may decline to act. If another MS does not volunteer within 6 days, then the proposed RMS must accept the lead.
The assessment of trials will take place in two stages. Part I is a joint scientific assessment by the member states, coordinated by the RMS to determine whether the trial is acceptable. Part II is the country specific assessment by each participating member state. Parts I and II may be submitted together, or part I can be submitted initially for review and agreement followed by the submission of part II, which can occur up to 2 years after part I information was provided.
A significant advantage of the new regulation is the instatement of more economical timelines for the assessment of applications. Validation must be completed within 25 days, part I assessment should be complete within 45 days (which can be extended by 50 days for clinical trials involving an advanced therapy investigational medicinal product and by an additional 31 days if further information is requested from the sponsor), and part II assessment should also be complete within 45 days (or 76 days for further information). If submitted together, then the overall timings may be between 60 and 106 days.

Risk-adapted management
The regulation sees the birth of ‘low intervention trials’ which describes a trial with very low risk compared to standard care. Such trials are subject to less stringent regulation in areas such as monitoring, requirements for the contents of the master file and investigational medicinal product traceability.
On the surface, this also appears to offer a way for applicants to obtain marketing authorisation for several indications based on “low intervention” trials. Clinical trials are considered “low intervention” for the testing of a drug used beyond its authorised indications. As a result, pharmaceutical companies may be able to apply for a license for a single narrow indication with data from small-scale clinical trials. Subsequently, additional indications can possibly be applied for based on “low intervention” trials4.

More pros than cons
There are some potential issues to be considered with the new regulation. How will the IT systems of each member state be made compatible? How can it be ensured that the ethics committee approvals are gained nationally but within a similar timeframe? Will the workload for popular RMS’ be overwhelming, as is currently the case with the decentralised procedure? Is 12 calendar days for applicants to respond to questions too rigid and demanding?
Whilst such questions need to be carefully considered, from our point of view the new regulation represents a clear, although only theoretical at present, improvement upon existing practices. The possibility of a clinical trial approval within 60 days should do much to restore the waning clinical trial activity in Europe. Moreover, a streamlining of the application process will be ardently applauded by regulatory professionals across Europe. The switch from providing a multiplicity of data to adhere to country specific requirements to a single submission via the portal and a single scientific assessment is a rational approach that should reduce the time and cost it takes to request a trial in Europe.
The regulatory community seems to concur. Here at Diamond BioPharm, the Head of Regulatory Affairs, Nicholas Littlebury, has identified learning and communication as fundamental keystones for the new regulation. “The centralisation of clinical trial submissions in Europe will rely heavily on effective communication between the various health authorities and sponsors within the regulations initial implementation period. All parties will need to ensure that there is continued effective learning to ensure that the overarching goals of the new regulation can be achieved. This should ultimately lead to a better process for conducting Clinical trials throughout the European Union”. The European Federation of Pharmaceutical Industries and Associations (EFPIA) called the proposal “an important step towards a much needed simplification and standardisation of clinical trials administration”.

How Diamond BioPharm can help
Diamond BioPharm Ltd are an EU regulatory affairs and product development consultancy based in the UK. Our experienced team have extensive experience undertaking clinical trial related activities including the writing and reviewing of IMPDs and Investigator Brochures along with full clinical trial application preparation, submission and coordination in Europe. Our team remain vigilant to upcoming changes in the regulatory landscape and look forward to undertaking clinical trial applications under the new regulation.


  1. Official Journal of the European Union, Regulation (EU) No 536/2014. (accessed 09/03/2015).
  2. NHS Confederation. The New EU Clinical Trials (accessed 09/03/2015).
  3. National Institute of Health Research. New EU CT Regulation: An interview with Tanya Simmons. (accessed 09/03/2015).
  4. The European Consumer Organisation. New European Clinical Trials Regulation: a major advance in transparency, to be confirmed. (accessed 09/03/2015).
13 March 2015