Clinical trials - Regulation EU No 536/2014
Although the Regulation entered into force on 16 June 2014 the timing of its application depends on the development of a fully functional EU clinical trials portal and database, which will be confirmed by an independent audit. The Regulation becomes applicable six months after the European Commission publishes a notice of this confirmation. The entry into application of the Regulation is currently estimated to occur in 2019.
The Regulation will ensure a greater level of harmonisation of the rules for conducting clinical trials throughout the EU. It introduces an authorisation procedure based on a single submission via a single EU portal, an assessment procedure leading to a single decision, rules on the protection of subjects and informed consent, and transparency requirements.
It will also make it easier for pharmaceutical companies to conduct multinational clinical trials, which should increase the number of studies conducted within the EU. More detailed information on the regulation is available on the European Medicine Agency (EMA)'s website.
EU Clinical Trial Portal and Database
Articles 80 and 81 of the Regulation assign the EMA the task of creating an EU Portal and Database. The EU Portal will be a single entry point for submission of data and information relating to clinical trials required by the Regulation. The EU Database will contain all data and information submitted via the EU Portal.
The EU Portal and Database will be the backbone of the new regime for clinical trials in Europe. It will considerably facilitate the application for clinical trials authorisation, in particular in case of multinational clinical trials, to the sponsor; the assessment carried out by national authorities; and access to clinical trials information by the general public.
The EMA together with the EU countries and the Commission are currently working in order to set up the portal and database. On 14 December 2014 the EMA Management Board endorsed the Functional specifications of the EU portal and EU database to be audited.
EMA's Management Board endorsed a timeframe for the delivery of the Portal and Database in December 2015. However, due to technical difficulties with the development of the IT systems, the portal’s go-live date had to be postponed and therefore the EU Clinical Trial Regulation will come into application during 2019 instead of October 2018, as previously scheduled. For further information please consult the EMA website.
The Clinical Trials Regulation provides more transparency on clinical trials data. All information in the EU database will be publically accessible unless its confidentiality can be justified on the basis of:
- Protection of commercially confidential information
- Protection of personal data
- Protection of confidential communication between EU countries
- Ensuring effective supervision of the conduct of clinical trials by EU countries
To support the transparency requirements of the Regulation, EMA has added two sets of requirements to the functional specifications for applying the exceptions:
- Features to support making information public
- Disclosure rules describing the practical implementation of the transparency rules.
The EMA Management Board endorsed both documents in 2015:
- Revision of section 6 of the "Functional specifications for the EU portal and EU database to be audited" setting out features to support making information public
- Appendix, on disclosure rules, to the "Functional specifications for the EU portal and EU database to be audited"
The Regulation simplifies the rules on safety reporting:
- The protocol may provide that not all adverse events (AE) and serious adverse events are recorded and reported.
- For a clinical trial involving more than one investigational medicinal product (IMP) a single safety report can be submitted in the Clinical Trial Eudravigilance database.
- Suspected unexpected serious adverse reactions (SUSARs) can be reported via the database.
Commission legal obligations in the context of Regulation (EU) No 536/2014
The inspection of clinical trials may concern good clinical practice as regards the conduct of clinical trials as well as good manufacturing practices as regards the manufacturing of the investigational medicinal products.
For clinical trials submitted on the basis of the Regulation, the Implementing Regulation (EU) 2017/556 of 24 March 2017 on detailed arrangements for the good clinical practice inspection procedures pursuant to Regulation (EU) No 536/2014 of the European Parliament and of the Council will apply.
The Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017, supplementing Regulation (EU) No 536/2014 of the European Parliament and of the Council, will apply to all clinical trials authorised on the basis of the Clinical Trials Regulation. It specifies principles and guidelines for good manufacturing practice for investigational medicinal products for human use, and arrangements for inspections. Complementary to this, the detailed Commission guideline, adopted on 8 December 2017, on the good manufacturing practice for investigational medicinal products, pursuant to the second paragraph of the Article 63(1) of Regulation (EU) No 536/2014 was adopted on 8 December 2017.
Both Regulations and the guideline will become applicable at the same time as Regulation (EU) No 536/2014.
Clinical trials conducted outside the EU
If clinical trials are conducted outside the EU, but submitted for marketing authorisation in the EU, they have to follow similar principles to the provisions of the Clinical Trials Directive (Annex I, point 8 of the Directive 2001/83/EC.
Clinical trials conducted outside of the EU should also be conducted in accordance with principles equivalent to those of the regulation as regards the rights and safety of the subject and the reliability and robustness of the data generated in the clinical trial.
This data should only be submitted in an application if the clinical trial has been registered ahead of time in a public register which is a primary or partner registry of, or a data provider to, the WHO ICTRP. The same applies to data gathered from a clinical trial that took place before the date of application of the regulation, or if the results have been published in an independent peer- reviewed scientific publication.