Session 1: The hospital pharmacist and Advanced Therapy Medicinal Products (ATMPs): what is/are the right hospital pharmaceutical technology/technologies?
2 Roanne Hospital, France
3 Pitié-Salpêtrière Hospital, Paris, France
ATMPs are biological medicines for human use that are based on genes, cells or both. They offer innovative opportunities for the treatment of diseases and injuries. ATMPs are approved for different clinical uses or in clinical trials, and we are now in charge of handling it. The aim of this workshop is to think about the design of our future aseptic unit.
The late 1990s saw the arrival of new biological products: gene therapy products and cell therapy products. In 2003, Europe gave them the status of medicines for which the current definitions are:
- Gene therapy medicinal product (GTMP) means a biological medicinal product which has the following characteristics:
- it contains an active substance which contains or consists of a recombinant nucleic acid used in or administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence;
- its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence.
GTM products shall not include vaccines against infectious diseases.
- Somatic cell therapy medicinal product (SCTMP) means a biological medicinal product which has the following characteristics:
- contains or consists of cells or tissues that have been subject to substantial manipulation so that biological characteristics, physiological functions or structural properties relevant for the intended clinical use have been altered, or of cells or tissues that are not intended to be used for the same essential function(s) in the recipient and the donor;
- is presented as having properties for, or is used in or administered to human beings with a view to treating, preventing or diagnosing a disease through the pharmacological, immunological or metabolic action of its cells or tissues.
They are to be distinguished from cellular "therapy" preparations (CTP) that are not subjected to substantial manipulation and are used for the same essential function (s). CTPs fall under the scope of Directive 2004/23 / EC for "transplant" and are not pharmaceutical.
In 2007, in view of the evolution of these medicines, in particular in regenerative medicine, Europe confirms their status as medicines by adding two new types to it in the European regulation CE 1394/2007 of November for which the definitions are:
- Tissue engineered product (TEP) means a product that:
- contains or consists of engineered cells or tissues, and;
- is presented as having properties for, or is used in or administered to human beings with a view to regenerating, repairing or replacing a human tissue
- Combined advanced therapy medicinal product (Combined ATMP) means an advanced therapy medicinal product that fulfils the following conditions:
- it must incorporate, as an integral part of the product, one or more medical devices within the meaning of Article 1(2)(a) of Directive 93/42/EEC or one or more active implantable medical devices within the meaning of Article 1(2)(c) of Directive 90/385/EEC, and
- its cellular or tissue part must contain viable cells or tissues, or
- its cellular or tissue part containing non-viable cells or tissues must be liable to act upon the human body with action that can be considered as primary to that of the devices referred to.
Moreover, in France, the "hospital exemption" of the European regulation CE 1394/2007 has been transcribed into a “ATMP prepared punctually” (ATMP-pp) which have specific quality standards and are used within the same Member State, in a hospital, under the exclusive professional responsibility of a physician, to carry out a prescribed medical prescription for a product specially designed for a particular patient.
How are ATMP supported ?
Pharmaceutical aspect, whether under an authorization (AMM or process authorization for an ATMP-pp) or in a clinical trial, appears to be similar and may require the following means:
- cryopreservation in nitrogen or other forms requires equipment, facilities, formations and the respect of specific handling and safety rules, preservation between + 2 ° C and + 8 ° C at -20 ° C and -80 ° C are already known and mastered;
- defrosting of the cryopreserved drugs, mainly cellular, will impose equipment, specific facilities as well as the learning by the personnel of the operating modalities;
- finally, in the context of a genetically modified drug, GTMP or not, the drug circuit must comply with the required containment conditions, including preparation waste.
As the hospital pharmacist takes responsibility for this, he must have complete control of the means allocated to him: personnel, premises, equipment...
What added value in development?
The development of an ATMP, pp or not, calls for:
- in compliance with the requirements of the don regulation (Directive 2004/23 / EC) and its qualification;
- for the production, to the complex techniques of Biology such as cell culture, the production of vector requiring to obtain a transgene, to produce a master cell bank then working cell bank, or transfection of cell ...;
- for quality control, analytical biology techniques such as multiparametric flow cytometry, high throughput sequencing, "omics" techniques and the analysis of massive data generated by these high-speed techniques.
Certainly, these regulatory aspects and techniques seem to be far removed from the "standards" of pharmacy, especially pharmaceutical technologies. However, while it will be necessary for those involved in the development of ATMP to integrate these 3 aspects into their field of competence, the hospital pharmacist is a specialist of the production of the medicinal product. In fact, he possesses the mastery of good practices, specific equipment and facilities such as controlled areas, qualification of raw materials and packaging products ... His skills and experience gives him this pharmaceutical added value inevitable to bring these future candidates medicinal products to their authorization to be made available to the patients.