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The New EU Clinical Trials Regulation: Ready for Implementation

The New EU Clinical Trials Regulation: Ready for Implementation
04 August 2016

By Dr. Martine Dehlinger-Kremer, VP, Global Medical and Regulatory Affairs

The new European Union Clinical Trials Directive, anticipated to go into effect in October 2018, is expected to be a major improvement over the previous Directive 2001/20/EC. Meant to both simplify the submission of an application dossier for authorization and harmonize the procedures for conducting clinical trails, the new legal Regulation’s goals include:

  • Making the European Union more attractive for clinical trial research by reducing costs
  • Reversing the decrease in the number of clinical trials conducted in the EU
  • Maintaining high standards of patient safety

Prior to becoming effective, the EMA must have established an operational database for clinical trials and a portal for submissions. Six (6) months after these two components are functional, the Regulation comes into full effect.

The scope of the Regulation is extensive, with several primary components covered in the core text and multiple appendices, including: authorization procedures; start of trial; suspension or temporary holds; early termination; protection of subjects; informed consent; conduct of trials; safety reporting; IMP manufacturing, labelling and import; and insurance

Certain aspects are not covered by the Regulation and remain country specific, such as ethical considerations, legal representation, site requirements and some administrative procedures. That said, there are several advantages brought by the new Regulation. The most important of these are:

  • A harmonized application dossier that covers regulatory and EC approval
    • Part I – Study specific documents – The concerned Member States cooperate in the assessment of scientific, therapeutic and safety aspects
    • Part II – Country/site specific documents – The assessment is made by each concerned Member State individually, applied to items such as biological samples, clinical trial agreements, informed consent, recruitment of subjects
    • Parts I + II – Can be reviewed in parallel or sequentially, depending on the sponsor’s preference
  • A national level body reviews the documents, with just one contact point and one fee per country
  • Efficiency has been enhanced through:
    • A single portal for the submission of the clinical trial applications, no matter how many countries are involved
    • A single decision through the EU portal
    • New member states assess only Part II, with Part I remaining valid as already approved, unless there is a disagreement on the basis of circumstances permitted, such as safety, data reliability and robustness of the considerations
    • Review timelines are established, with a total time of 106 days allowed for the initial submission; advanced therapy trials can take up to 156 days

By harmonizing these requirements, submissions have been simplified from what might have been a total of 28 submissions to just one!

Impacts on Sponsors

Co-sponsorship: Under the new Regulation, co-sponsorship is now permitted, with each co-sponsor assuming full regulatory responsibility unless co-sponsors agree otherwise.

Monitoring: The extent and nature of monitoring is determined by the sponsor. Monitoring can be flexible based on the intervention level, objectives and methodology of the trial, and the degree of deviation of intervention from normal clinical practice.

Safety reporting: SUSARs are required to be electronically reported by the sponsor directly into EudraVigilance, instead of being submitted to each Member State. If an electronic report is not possible, then the adverse event should be reported to the country where the SUSAR occurred and they are to enter it into EudraVigilance.

Transparency: Results will be made publicly accessible in the EU database. Detailed summaries of the study results, including a summary in plain language, are to be submitted within one year of termination of the clinical trial. Final study reports that were submitted to support a marketing authorization are to be uploaded onto the EU database within 30 days of authorization, rejection, or withdrawal of the marketing application. Sponsors are subject to penalties if they fail to adhere to these transparency obligations.

Clinical trial data submitted in an application dossier must be based on clinical trials that have been registered, prior to their start, in a public registry that is a primary or partnered registry of the international clinical trials registry platform of the World Health Organization. For trials started before the Regulation applies, publishing in an independent peer-reviewed scientific journal is accepted as well. If trial data from the US is to be considered for the EU marketing application, then it must be registered prior to start, rather than within 21 days after recruitment start as typically required in the US.

In summary, the new EU Regulation on Clinical Trials is expected to be a major improvement over the previous CT Directive and will:

  • Streamline the approval process for studies conducted across multiple Member States
  • Make one single application sufficient for conducting clinical trials in several Member States
  • Harmonize the regulation of clinical trials throughout the Member States
  • Simplify reporting procedures
  • Increase the transparency of clinical trial results.

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