Masterstudiengang "Drug Regulatory Affairs"


Making cellular therapies available to patients - Possible regulatory pathways in Europe and Germany ***

Christophe Klumb (Abschlußjahr: 2011)

Language: English

Cellular therapies have been rapidly evolving in the last years and the opposition between regulation and scientific innovation is seemingly increasing since the introduction of the new Advanced Therapy Medicinal Products (ATMP) Regulation in Europe. On the one hand it is clear that such revolutionary therapies need to be controlled having in mind the experimental and scientifically unsubstantiated clinical applications that used to be performed with stem cell therapies in Europe, and especially in Germany such as the injection of bone marrow stem cells in the brain supposedly to treat Parkinsons disease. On the other hand the plan enunciated by the Committee for Advanced Therapies (CAT) to foster scientific innovation in the field of advanced therapies does not seem achieved taking account of the one and only ATMP that was granted a centralised marketing authorisation since 2009 and the stagnation or even decrease in the yearly ATMP applications.

Depending on the nature and the function of the cells involved in a cellular therapy a classification of the latter is made determining the way of authorisation it has to follow: centralised marketing authorisation for ATMPs or national accreditation for blood stem cells for example (CD34+ haematopoietic stem cell grafts after chemotherapy). Some provisions of the legislation regarding cellular therapies leave some room for interpretation, which can in turn mean that developers and regulators may come to another classification of a cellular therapy and thus another way of authorisation. This can be an opportunity for developers if they can achieve acceptance of their argumentation by the regulators. The complexity of the European legislation can also lead to misinterpretation if the law texts are not read in the right order. Starting a classification directly reading the ATMP Regulation will certainly lead to an ATMP classification whereas starting with the medicinal product mother Directive could lead to scope exclusion (e.g. for autologous bone marrow isolated stem cells used in the same surgical procedure that are not actually placed on the market). The impact of the classification of the cells on the availability delay of the cellular product is determinant. A maybe faster and simpler way of bringing cellular therapies to the market would be the use of the medical device route. Cells that are gained or processed through a medical device could be the object of an authorisation together with this device, which would have a clinical end point in its intended use. Thus medical device clinical investigations could be performed and therapies linked to the use of the medical device could be authorised on the European market under the CE mark. The medical device authorisation pathway is simpler but still guarantees quality, safety and efficacy.

But there are other ways than a marketing authorisation to make cellular therapies available to patients such as the participation in clinical trials or in compassionate use programmes. Whereas the requirements and provisions for clinical trials are harmonised on the European level, compassionate use programmes remain in the responsibility of the Member State and not everyone have implemented a legislation to regulate them.

When the cellular therapy is on the market, it does not mean that patients directly have access to it. For products with marketing authorisations, adequate reimbursement strategies must be set-up so that patients and national healthcare systems can afford use them. Clinical trials do not present this drawback for patients, as the access to the cellular product being assessed is free of charge for the patients. So it is as well within compassionate use programmes in Germany. On the other hand, what is an advantage for patients leads to the absence of retribution for the developers of the therapies, which may threaten their existence.

Thus, improving the availability of cellular therapies to patients in Europe and Germany is mainly but not only a regulatory task.

Total pages: 49
Annexes pages: 11

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