The set of the authorized texts that governs this therapeutic domain has been elaborated thanks to the works of the professionals involved in this therapeutic activity under the initiative of the French Establishment of the Grafts, a public establishment administrative in nature and the French Society of Hemapheresis which brings together the various actors of the apheresis in France.
The regulation concerns:
•The cellular therapy activity.
•The staff involved in the withdrawal and the transformation of the product.
•The material necessary for the withdrawal and the transformation.
•The cellular product itself.
•The eventual clinical tests done.
•The cautions to exercise.
The cellular therapy activity has been defined as “the administration of autologous, allogeneic or even xenogeneic cells, to the man with the goal to prevent, to treat or to attenuate an illness”. A legal framework governing this activity has been put in place and is governed by the bioethic law of July 29, 1994, various measures of social and statutory sanitary order of May 28, 1996 and the “sanitary security” law of July 1st, 1998.
The extracorporeal photochemotherapy (ECP) is within this definition and an authorization delivered by the decentralized services of the state for the withdrawal and the administration of the cells, sensitized and irradiated, is indispensable to undertake this activity.
The staff involved in the withdrawal are the physician and graduate nurses of state. The staff involved in the transformation of the cellular product is physician, pharmacist, biologist and technician of laboratory.
The entire staff must conform to the rules of good practices as they appear in the decree of December 1998 requiring, notably, the existence of a system of quality insurance.
The material of withdrawal and irradiation is submitted to the same rules of good practices as well as the relative regulation to the medical devices (decree of February 4, 1995) and to the part of the “hospital law” (Article L.712-12) relating to the heavy equipment that is indispensable to carrying out the therapeutic activities at high costs.
The cellular product and the process used to arrive at the product administered to the patient must receive an authorization of the French agency of sanitary security and sanitary products (Afssaps) according to the decree of October 1st, 2001.
The 8-methoxy psoralen (8-MOP) used at the time of the ECP does not have statute really clarified in France between a product having to receive a temporary authorization of use (ATU) and a supplementary therapeutic product (PTA).
However, the 8-MOP, as used in the ECP would not need a demand for marketing authorization (AMM), which means that it fits within the definition of a product with an ATU. Therefore, it seems that the 8-MOP as used today in the ECP should be considered like a supplementary therapeutic product (PTA).
The conditions of marketing and use of these supplementary therapeutic products will be fixed by a decree. Their authorization will be given by the Afssaps.
The debate is not closed and the difficulty to get this product in this therapeutic application should be raised in order not to deprive the patients of a therapeutic product which has given good results in some conditions, and merits to be valued in other conditions, during clinical tests.
The clinical tests of cellular therapy must be allowed before they are operational and this authorization is given by the Afssaps according to the decree of October 1st, 2001 and modes fixed by decree.
Finally there are regulations that define the cautions to exercise for all therapeutic products. With regard to the ECP, the concerned cautions are the materiovigilance defined in the articles R.665-48 to R.665-64, the biovigilance in application of the L.1211-7 article of the code of the public health.
In conclusion, the recommendations for the professionals who practice the ECP in France would be to complete a file of authorization to set in motion this cellular therapy, to conform to the rules of good practices, including the setting up of a system of quality insurance, to declare the incidents linked to the materials and the products used, to assure the follow-up of the administration of the cellular product at the patient.
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