Studies on medicinal products with human subjects
In the nineties of the last century, a legal framework for clinical trials on medicinal product with human subjects was sought within the European Union. The underlying motive was that the European Union should become an interesting region for the pharmaceutical industry.
In 1995, the European Commission presented their proposal for an EU directive which was followed by complex negotiations between representatives of the Member States and debate in the European Parliament. Gradually, ethical discussions were getting more and more consideration in the debate.
On 21 November 2000 the amended directive was adopted by the European Parliament. Three weeks later also the European Council also approved the definitive Good Clinical Practice Directive (Directive 2001/20/EC) in the conduct of clinical trials with a medicinal product.
The EU Good Clinical Practice Directive (Directive 2001/20/EC) regulates clinical trials with medicinal products including the Advanced Therapy Medicinal Products (i.e., gene therapy medicinal products (GTMP
), somatic cell therapy medicinal products (sCTMP), tissue-engineered products (TEP) ), xenotransplantation, vaccines, and clinical trials with genetically modified organisms (GMOs).
The introduction of the Good Clinical Practice Directive in 2001 made it necessary to adapt the Dutch WMO for studies on medicinal products with human subjects. An important change was the introduction of a dual assessment system. The EU directive is based on a review by both a Competent Authority and an MREC. Until then, the Netherlands, only had a single review by an accredited MREC or in special cases a single review by the CCMO.
In most EU member states the directive was incorporated into national legislation by May 1st, 2004. Due to the discussions in the Dutch Senate, the introduction of the directive in the Netherlands was delayed. On March 1st, 2006 the amended WMO - which now included the directive - finally came into effect.
The discussions in the Dutch Senate resulted in a delay of the implementation of the EU directive in the Netherlands.
The Dutch government choose for an implementation that as much as possible in accord with newly (in 1999) introduced WMO and the existing situation of the decentralized review by accredited MRECs. As a result, the integral and multidisciplinary assessment of the entire research file by the recognized MRECs remained in place and the Competent Authority would do marginal review of the research file.
In order to guarantee that the MRECs would have the appropriate expertise on board for the review of studies on medicinal products, two disciplines (i.e., clinical pharmacology and pharmacy), were added to the mandatory composition of the accredited MRECs.
As a result of the implementation of the EU directive the CCMO became the Competent Authority of studies on medicinal products that are reviewed by the accredited MRECs. In some special cases (e.g., gene therapy and somatic cell therapy trials and trials with unlicensed vaccines) the CCMO - and not an MREC - is the reviewing committee. In these cases the Minister of Health Welfare and Sports is formally the Competent Authority.
In practise the Dutch Medicine Evaluation Board (MEB) acts as the Competent Authority in behalf of the Minster, as we briefly explained in the first theme Explaining the Dutch Review System.
For gene therapy and somatic therapy trials, studies with nucleotides and unlicensed vaccines, and non-therapeutic intervention research with minors and incapacitated subjects the CCMO (and not an MREC) is the reviewing committee. For these cases, the Ministry of Health, Welfare and Sports is formally the Competent Authority. The Ministry has mandated this task to the MEB. For all other trials with medicinal products, the MREC is the reviewing committee and the CCMO the Competent Authority.
On 16 April 2014 the EU Clinical Trial Regulation (EU no 536/2014) has been published which introduced a new system of submission and assessment of clinical trials with investigational medicinal products. This regulation will be in force from January 31th 2022 onwards.