On 30 December 2008, the European Regulation on Advanced Therapy Medicinal Products ("Regulation 1394/2007" or “ATMP Regulation”) came into force. Like any other European Regulation, it has direct effect in all its provisions, and does not require any implementing measure in order to be enforced in the Member States. Since 30 December, any new ATMP has to comply with the provisions of Regulation 1394/2007.
The first ATMP to be authorised is the ChondroCelect, developed by the Belgian company TiGenix. It was authorised by a Commission decision of 5 October 2009.
The ATMP Regulation is part of a legal framework which encompasses the regulatory provisions applicable to cells and tissues. As a matter of fact, Regulation 1394/2007 provides that the donation, procurement and testing of those cells or tissues have to be made in accordance with Directive 2004/23/EC of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (hereafter, "Directive 2004/23"). Directive 2004/23 provides that those operations have to be performed in so-called “tissue establishments”.
Therefore, the implementation of Directive 2004/23 in the Member States was crucial for the actors of the pharmaceutical industry that intend to develop ATMP. In Belgium, the implementation process of Directive 2004/23 is now close to completion. It is the purpose of the present contribution to provide a general overview of the new Belgian legislation applicable to cells and tissues, which (partially – see below) entered into force on 1 December 2009. It does not examine the other aspects of the legislation on ATMPs, which are laid down in the pharmaceutical legislation, more specifically in the ATMP Regulation. The precise focus of this text is the implementation of Directive 2004/23 in Belgium, and its implications on the manufacturing of ATMPs.
The law of 19 December 2008
The first parliamentary discussions on the implementation of Directive 2004/23 date back to 2006. The legislative process resulted in the adoption in Belgium of the law of 19 December 2008 on the procurement and use of human corporal material intended for medical human applications or for scientific research (hereafter LHCM).
Its scope is broader than the scope of Directive 2004/23. First of all, the LHCM is intended to apply to scientific research, be there a human application or not in the framework of that research. Whereas Directive 2004/23 only applies to the cells or tissues intended for human applications, and scientific research without human application thus falls outside the scope of Directive 2004/23.
Secondly, as far as ATMPs are concerned, the LHCM does not limit its scope to the donation, procurement and testing of the human corporal material intended for the manufacturing of such products. It is, in principle, applicable to all operations carried out on human corporal material intended for the industrial manufacturing of ATMPs. However, a specific regime is provided for autologous ATMPs, for which the standards of quality and safety are only applicable to the donation, procurement and testing phases, the other operations being solely subject to the standards applicable to ATMPs, as defined in the pharmaceutical legislation. For allogeneic ATMPs, the standards of quality and safety apply throughout the whole manufacturing process, in addition to the standards defined in the pharmaceutical legislation. This differentiation made by the Belgian legislator between autologous and allogeneic ATMPs, which does not exist in the European legislation, creates an overlap between the quality and safety requirements resulting from the legislation on cells and tissues and the pharmaceutical legislation respectively.
The LHCM makes a distinction between four types of structures: the banks for human corporal material ("BCM"), the intermediary structures ("IS"), the production establishments ("PE") and the biobanks. The BCM must be operated by hospitals and can be accredited to perform any operation with the human corporal material. The IS may be accredited for the processing, preservation, storage and distribution of human corporal material, but they have to conclude an agreement with a BCM in order to do so. The PE can be accredited to perform any operation (testing excepted) without the consent of a bank, as far as the human corporal material is intended for the industrial manufacturing of autologous ATMPs. Finally, the biobanks are structures accredited to store human corporal material and make it available, exclusively for scientific research purposes provided it is not intended for any human application.
The LHCM organises different regimes, depending whether the human corporal material is intended for the manufacturing of ATMPs or not. If it is intended for the manufacturing of ATMPs, a distinction must be made between the autologous ATMPs and the allogeneic ATMPs.
Allogeneic ATMPs may only be produced in a BCM or an IS that concluded an agreement with a BCM. The autologous ATMPs may only be produced in a PE. In this case, the human corporal material may be transferred directly from the place where it has been collected to the PE, without having to transit through a BCM. In all other hypotheses, the human corporal material has to transit through a BCM.
The system organised by the LHCM is rather complex. Moreover, not less than six Royal Decrees implementing its provisions have been published in the Belgian Official Gazette so far. Those Royal Decrees relate to the general requirements applicable to BCM, IS and PE, to the quality and safety standards for the operations performed on human corporal material, to the hospital standards, to the notification of serious adverse reactions and events, and to the specific regime that is applicable to reproductive cells. The LHCM and the first Royal Decrees entered into force on 1 December 2009.
The Federal Agency for Medicines and Health Products is in charge of the surveillance of the compliance of the activities carried out with cells and tissues.
Aside from the implementation measures cited above, other decrees are worth mentioning here, notably the Royal Decree of 7 December 2008 on the conditions applicable to the intervention of the mandatory healthcare insurance in the costs of delivery of human tissues and establishing the list of those tissues, as well as the Ministerial Decree of 14 October 2009 determining the price of human corporal material.
A seventh Royal Decree, defining the specific regime applicable to biobanks, should be published shortly. It is currently under review by the legislation division of the Council of State. When the regime specific to biobanks will enter into force is not yet known with certainty. However, it can already be stated that this regime will provide for an accreditation procedure which will require a favourable opinion of an ethics committee. Once the accreditation is granted, no additional opinion of the ethics committee will be required in the course of the biobank’s activities, as long as those activities fall into the scope of the accreditation itself.
It is crucial for the healthcare biotechnology sector to follow the implementation process closely, as critical aspects of their activities fall into the scope of the new legal framework.