Pilot project for new Clinical Trial Regulation
In 2020 the new clinical trial regulation 536/2014 (CTR) is foreseen to enter into force. This important change in legislation targets administrative simplification and harmonization in Europe.
An important, preparatory step is a pilot project to obtain experience and align processes between all participants. The CTR pilot is organised in collaboration with the ethics committees. The procedure to authorise the trial will follow the national legislation of 7th May 2004 but the dossier to be sent and its evaluation will follow the spirit of the new regulation and the draft Belgian law.
Sponsors of trials are invited to express their intent to become a candidate for the pilot. Sponsors are helping FAMHP to recognize obstacles and to streamline the procedure and will off course obtain useful experience prior to the entering in force of the new regulation. If you are willing to express your intent please fill out this form and send it to CTRpilot@afmps.be.
As from the 15th of February 2021, a system with time slots has been introduced within the Division R&D for all initial dossiers applications via the CTR pilot. Further information and the link to this reservation system can be found below. Initially, the time slots were opened for each month at a time, however, in order to have more predictable timelines for sponsors of clinical trials, the time slots for the June-July-August will be opened at once. This will take place, as before, on the first Friday of May (7th of May 2021). Time slots for September-October-November will be opened on the first Friday of August (6th of August 2021).
Submitting an application
Each clinical trial protocol is identified at European level with a unique number. This number has to be asked by the requesting company in the EudraCT database before submission of any demand. The European application form, wich is part of the dossier, has also to be completed in the EudraCT database.
A clinical trial can only start after receiving a favourable opinion from the Ethics Committee ( recognized Ethics committees ) and if the relevant authority (FAMHP: R&D) has not indicated any major insufficiency within the legal timeframe provided for in the law dated 7th May 2004 related to experiments on human people.
The application must be sent via CESP to:
Federal Agency for Medicines and Health Products
Research and development division
Galileelaan - Avenue Galilée 5/03
Regarding the electronic submission via CESP (Common European Submission Portal) of CTA/CTR Pilot dossiers and substantial amendments to the R&D department, we kindly advise you to contact us if no confirmation of receipt has been received within 5 days.
The maximum time taken by FAMHP to give an opinion is 15 days for monocentric phase I clinical trials and 28 days for all other clinical trials with a possible clock-stop of maximum one month.
For formulating a CTA you will find all the details in the following document : " Detailed guidance for the request for authorisation of a CT on a medicinal product for human use : "CT Application". For Belgium only one copy of each document is required.
Submission of applications for clinical trials with GMO medicinal products:
For the submission of applications for clinical trials with GMO medicinal products please follow the guidance document: Belgian Regulatory Guidance On The Use Of Genetically Modified Organisms In A Clinical Trial
A Questions and Answers document and an overview of the regulatory requirements in most of the EU countries are also available on the European Commission website by following this link.
In view of the particular nature of the production method, it is possible to grant a "conditional approval" for the annual update of flue vaccines that have already been authorised.
This means that such a trial can be approved even if some data about the quality (in particular certificates of analysis) are missing. But that is only valid if these data are submitted to AFMPS one week before the start of the clinical trial and if the evaluation is positive.
Development safety Update Reports - DSUR
Once a year, during the entire duration of the experiment, the sponsor must provide the minister and the Ethics Committee in Belgium and those of the Member States on whose territory the trial is conducted in the case of a multicenter trial, a list of all suspected serious adverse events that have occurred during that period as well as a report on the safety of the participants pursuant to article 28, § 2 of the law of 7 May 2004 relating to experiments on human people.
Submission must only be made to the FAMHP via the Common European Submission Portal (CESP).
The following documents should be enclosed:
- The DSUR complying with the formatting mentioned in the ICH E2F guideline.
- The template "DSUR – submission for Belgium" (which can be copied and pasted)
- A signed cover letter
Guidance can be found here.
A fee is due for each DSUR submitted.
The FAMHP asks to wait for the structured invoice for the payment. More information on the payment method and the fee amount can be found here.
The European directive 2001/20 has been incorporated in national law by the law dated 7th May 2004 (French version) published in the Belgian Monitor of 18th May 2004. The new legal framework has been in force since 1st May 2004.
The law of 7 May 2004 has been modified several times (see below)
Note: the laws, royal decrees and circulars are (except for a few) not translated in English. Therefore we refer to the links on the French and the Dutch version of the website.
Law dated 7th May 2004 (French version) related to experiments on human people.
Modified by the following laws :
Royal Decrees (laws)
Royal Decree dated 30th June 2004 (French version) determining the measures for carrying out the law dated 7th May 2004 (French version) relating to experiments on human people concerning clinical trials of medicines for human use, modified by the
Royal Decree dated 15th July 2004 (French version) determining the fees to be paid for a request for an opinion or for authorisation to conduct a clinical trial or an experiment.
Circular 653 (French version): Clinical trial requests relating to COVID-19
Circular 613 (French version): Changes to the law of May 7, 2004 concerning experiments on human people.
Directive 2001/20/EC of the European Parliament and of the Council
Directive 2005/28/EC of the Commission laying down principles and detailed guidelines for good clinical practice.
Directive 2003/94/EC of the Commission laying down principles and detailed guidelines for good manufacturing practice.
Exploratory clinical trial: guidance (version 3 - June 2016)
Questions / Answers - FAQ's
For questions please send an e-mail to : CT.RD@fagg.be
European harmonization on specific topics with regards to clinical trials
At the moment, clinical trials are under national scrutiny. However, a lot of the scientific aspects are governed by European and/or international guidances. The success of the Voluntary Harmonisation Procedure (VHP) has made it clear that there are differences in interpretation of guidances.
The clinical trials facilitation group (CTFG), in which the FAMHP plays an active role, has discussed two aspects in detail and has made compromise proposals.
1) Good Laboratory Practice
Directive 2001/83/EC states that Non-clinical (pharmaco-toxicological) studies shall be carried out in conformity with the provisions related to Good Laboratory Practice. This Directive does not concern clinical trials. However, since Directive 2010/63/EU indicates that the care and use of live animals for scientific purposes is governed by internationally established principles of replacement, reduction and refinement, it would be expected that studies would be conducted according to GLP from the first time. Regulation 536/2014 (entry into force foreseen mid-2016) concerning clinical trials states that non-clinical information submitted in an application dossier shall be based on data derived from studies complying with Union law on the principles of good laboratory practice, as applicable at the time of performance of those studies. Thus it is made clear that in the future GLP conform studies will be requested in support of clinical trial applications. International guidance documents indicate that pivotal safety pharmacology studies and toxicology studies are expected to be GLP compliant. The issue was discussed at the Clinical Trial Facilitation Group and a document was published on their website (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_06_HMA_CTFG_GLP_in_clinical_trials.pdf) in order to lead to European harmonisation.
At Belgian level, a brief survey of sponsors of phase I clinical trials with medicinal products of chemical origin that were recently submitted in Belgium, indicated that all pivotal safety pharmacology studies (hERG, CNS, cardiovascular and respiratory) are indeed available according to GLP before the First in-Human study.
The main issue in the CTFG document is that as applications for CTA’s do not include individual study reports, Sponsors should include a statement confirming the OECD GLP status, either within the Investigator's Brochure (IB) or within the covering letter.
ICH M3 and ICH 5A guidelines indicate requirements for non-clinical data concerning potential reproductive toxicity. When clinical trial applications are submitted, little or no data exist concerning reproductive toxicity. This is particularly the case for early phase clinical trials. At a time where a benefit to the mother is not yet firmly established, damage to the unborn child must absolutely be avoided.
The Clinical Trial Facilitation Group has provided a document on their website that envisages harmonization of the requirements for clinical trial applications throughout Europe (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf). This document is intended for ALL clinical trials that are submitted. Sponsors are asked to pay attention to this document and to clearly justify their strategy for contraceptive measures during clinical trials.
- Belgian pharmaceutical conference - 17/04/2012
One of the main sessions during the Belgian Pharmaceutical Conference (Terhulpen, 17th of April 2012) covered clinical research in Belgium. An important topic, because clinical research is more then just a way to gather evidence for future medicinal products : it is also an important job creator (almost 30.000 jobs in Belgium). For patients, the participation to clinical trials can mean an early access to innovative medicines. Belgium is one of the bigger research countries in Europe : 9% of the clinical trials in Europe are performed in Belgium.
The current situation on clinical trials has been investigated by Ingrid Maes, Director Strategy & Operations Pharma & Healthcare of PwC. The FAMHP’s database on clinical trials was investigated, and a survey was held with representatives of various stakeholders.
The results of this investigation were presented – the presentation can be downloaded HERE.
Federal Agency for Medicines and Healthproducts
Research and development department
Galileelaan - Avenue Galilée 5/03