iSpeak Blog

Introduction to EU Clinical Trial Regulation No. 536/2014


EU Directive 2001/20/EC worked to simplify and harmonise the administrative provisions governing clinical trials.  It was, and remains, a good attempt but many hold the opinion that the full benefits of the directive haven’t been realized based on variations in local implementation.  Recognizing the challenges this created for running a clinical trial in several member states simultaneously and with the goal of encouraging clinical study sponsors to conduct trials across member states, the European Parliament and the Council of the European Union enacted new EU Clinical Trial Regulation No. 536/2014 on 16 April 2014. Once EU Clinical Trial Regulation No. 536/2014 becomes effective, EU Directive 2001/20/EC, to the extent that it concerns investigational medicinal products, will be replaced by the new Regulation.   Clinical trials that started before the new Regulation becomes effective may continue utilizing the rules in the original Directive for a period of 3 years from the Regulation’s effective date.  Further, sponsors can opt for the ‘old system’ within one year of the Regulation’s effective date and operate under the Directive for duration of a three year transition period. Unlike the previous clinical trial Directive, the new EU Clinical Trial Regulation, once effective, will be law governing the conduct of clinical trials across all member states.  The overarching change enacted by the Regulation is the centralization of the clinical trial application process.  Under the Regulation, a proposed study’s clinical trial application will be submitted electronically through a new electronic portal. The centralized submission will trigger review by representatives from the individual member states in which the sponsor is requesting the trial be conducted. Once an application is received, a single member state is chosen to lead the assessment (known as the “reporting member state”). 

In some cases, the reporting member state may be the member state that is requested by the sponsor, and in other cases, a member state may volunteer to lead the assessment.  With input from other member states as needed, the reporting member state validates the application or sends queries to the sponsor requesting further clarification of details.  The reporting member state will assess the validated application with respect to compliance, patient safety and scientific value.  An assessment report is sent to other member states for comment and the aggregated comments are then sent to the sponsor.  This can become an iterative process in which changes are made to study design prior to reporting member state study approval.  Although the study approval is done at the discretion of the reporting member state, individual member states can refuse to authorize the clinical study in their states. Beyond centralizing the application process, the EU Clinical Trial Regulation provides rules for conducting clinical trials that span from gaining a patient’s informed consent to the management of a study’s clinical drug supply.  These new rules may require those responsible for supplying study drugs to make changes to their business practices. 

In some cases, the changes will increase the efficiency of drug supply provision and in other instances there may be new challenges individual trial sponsors need to address.  Therefore, each organization’s clinical drug supply group should make its own thorough review of the pending Regulation for an early understanding of the new rules that may require changes to a firm’s current practice.  The reader should keep in mind that this new regulation may introduce subtle changes that could result in the need to evaluate, and possibly adapt clinical supply chain operations. This article along with our new monthly series are intended to  introduce new and different components of the EU Clinical Trial Regulation and where firms may need to consider changes to their clinical supply chain operations to ensure readiness when the new regulation comes into force.  The installments that follow will discuss specific considerations when providing drug supply for EU studies governed by the Regulation.  In an attempt to help the reader digest the ramifications of the change, the subjects of follow on papers have been segmented into descriptions and highlights of changes that pertain to different areas of drug supply such as but not limited to:

  • Investigational and Auxiliary Product Labeling
  • Use of Authorized and Unauthorized Auxiliary Products in Clinical Trials
  • Import and Release of Investigational Product
  • Clinical Trial Application Filing Process

Read the next installment in this series - Auxiliary Medicinal Products in EU Clinical Trials.  A diverse team of pharmaceutical industries peers organized by ISPE’s Investigational Products Community of Practice (IP COP) is writing these articles and hopes you enjoyed this introduction and the monthly series.  The COP encourages you to look for future briefs/posts as the IP COP dives into different aspects of the new Regulation in an effort to help the IP community be as prepared as they can for the new regulation!


  • Ted Bradley (Pfizer) – IP COP Task Team Contributor.
  • Hans von Steiger (Pfizer) – Regulation Introduction Author
  • Magali Busqet (Sanofi) – IP COP Task Team Contributor
  • Massimo Eli (Merck) – IP COP Task Team Contributor
  • Chuck Gentile (Sanofi) - IP COP Task Team Contributor
  • Juliette Kirk (Pfizer) – IP COP Regulatory Consult
  • Kirsteen Magee (Mylan) - IP COP Task Team Contributor
  • Marianne Oth (Eli Lilly) - IP COP Task Team Contributor
  • Bernd Steffens (Boehringer Ingelhiem) – IP COP Task Team Contributor
  • Martin Waldherr (Roche) – IP COP Task Team Contributor