New legislation: EU Regulation 536/2014

Regulation 536/2014 will replace Directive 2001/20/EC. This makes it an important regulation within clinical research. Some points that will change with the introduction of the regulation can be found below.

Terminology in the regulation

The regulation distinguishes between a study without intervention, clinical trial, clinical trial with limited intervention and a clinical study. These definitions can be found in recital 3 of the preamble, recital 54 of the preamble and Article 2 of the Regulation.

The regulation uses different definitions for drugs, i.e. investigational medicinal products, authorised investigational medicinal products, advanced therapy investigational medicinal products, auxiliary medicinal products and authorised auxiliary medicinal products. These definitions can be found in Article 2 of the Regulation.

New EU portal and EU database

To support the provision in the regulation, the EMA is building a new EU portal and database for clinical trials with medicines. This portal will replace EudraCT. Via the EU portal, a sponsor may submit a request for advice, approval or amendment to an application dossier. The EU database is publicly accessible. However, confidential information will not be publicly available. See also Article 81 of Regulation 536/2014.

Reporting a serious breach

A ’serious breach’ regarding the conduct of a clinical trial should be reported by the sponsor of the clinical trial (see Article 52 of the Regulation). Reference should be made to a serious breach when the protection and rights of a participating subject or the reliability and scientific value of the results of a clinical trial are affected.

A serious breach always occurs within the context of a clinical trial. An incident which is called a calamity in the Healthcare quality, complaints and disputes act is an unintended or unexpected event which relates to the quality of care and that results in the death of or serious harm to a subject.

The Regulation states that the sponsor is responsible for reporting serious breaches via the E-portal. The sponsor does so without undue delay and within seven days after he took note of the serious breach. In the event that the serious breach is also an incident which is called a calamity in the Healthcare quality, complaints and disputes act, it must also be reported to the Health and Youth Care Inspectorate (HYCI).

Compliance with protocol and good clinical practice

As in the WMO, the Regulation outlines that a clinical trial (with medicinal products) must be carried out in accordance with the applicable protocol and Good Clinical Practice. Article 47 of the Regulation states that the involved parties must take into account the quality standards and guidelines of the ICH-GCP on Good Clinical Practice.

Co-sponsorship of a clinical trial

The Regulation introduces the term co-sponsorship in Article 72. In a clinical trial with multiple sponsors, the responsibilities of the sponsor apply to all sponsors unless the sponsors determine otherwise in a written agreement that defines their respective responsibilities. If the agreement does not indicate to which sponsor a certain responsibility belongs, the responsibility rests with all sponsors.


On 16 April 2014, the European Parliament and the Council of the EU adopted this Regulation on clinical trials with medicinal products for human use. The purpose of the regulation is to ensure that European countries work more uniformly, thereby making it easier to conduct trials with medicinal products in different EU member states. Regulation 536/2014 will replace Directive 2001/20/EC.

For clinical trials with medicinal products it is important that the rights, safety, dignity and well-being of the subjects are protected and that the trial data are complete and reliable. The exact date of entry into force is not yet known. Information on the expected date when this Regulation will come into effect is described on the EMA website. First an independent audit must establish/confirm that the EU portal and the EU database have become fully functional and that the systems meet the functional specifications.

When this Regulation comes into effect, anyone who is involved in a clinical trial with medicinal products for human use must comply with the requirements of the regulation. A transitional provision applies to the regulation. This is described in Article 98 of the regulation. The most current information on the date of entry into force of the regulation can be found on the aforementioned website.

For more information on the Regulation, the following websites can also be consulted: