Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5653_Библиотеки_им_академика_М_И_Перельмана

Regulation (EC) No. 1394/2007, applied by the European Medical Agency (EMA) from 30 December 2008, was the rst to specically address cell, gene and tissue engineering thera­pies. It legislated an independent review of ATMP to guarantee high standards of quality, efcacy and safety equivalent to those of other pharma­ceuticals before a product is distributed to patients. Directive 2001/83/EC dened (i) gene therapy medicinal products (GTMP) and (ii) somatic cell therapy medicinal products (sCTMP), with subsequent addition of (iii) tissue- engineered products (TEP) and (iv) com­bined ATMP in Regulation (EC) No. 1394/2007.

Notably, classication in the United States by the Federal Drug Administration (FDA) differed since it highlighted only two product types, gene therapy and cellular therapy. Nonetheless, overall approval procedures for ATMP in both regions have strong similarities with expectation that greater regulatory convergence will help ATMP development globally [68]. Providing a central route for EU authorization of ATMP, the expert Committee for Advanced Therapies (CAT) inau­gurated in January 2009, helped establish classi­cations and certication procedures to support small and medium enterprises (SME) and com­panies in early phases of ATMP development, clarifying whether a product falls within the de­nition of an ATMP in the EU.From the very large number of applications for authorization, dispro­portionately few have been approved. This has not only reected the acknowledged deep intri­cacy of the therapeutic goals, but called into question whether the length and complexity of the regulatory procedures were themselves hav­ing detrimental consequences [57]. An unfortu­nate misguided impression would be that the regulatory framework is principally a signicant obstacle that needs to be overcome before wide­scale deployment of a new cell therapy. Likewise,

Three regulatory initiatives, namely, orphan drug (OD) designation, the hospital exemption (HE) clause and compassionate use (CU), have sought to mitigate hurdles, incentivize ATMP development and enable early patient accessibil­ity. The EMA’s Committee for Orphan Medicinal Products (COMP) is responsible for recommend­ing whether ATMPs apt for providing new medi­cines for rare untreatable diseases qualify for OD designation according to Orphan Medicines Regulation (EC) No. 141/2000. OD designation introduces incentives that compensate for small patient populations offering limited return on investment. This includes protocol assistance, reduced procedural fees and product market exclusivity for 10years after marketing authori­zation [44]. Most of the currently approved ATMP target orphan diseases. The HE clause, within regulation (EC) No. 1394/2007, allows ATMP manufacture to be authorized by a national competent authority (NCA) of the Member State rather than otherwise mandatory centralized mar­keting authorization procedures. Thereby, patients may benet from specic ATMP treat­ments when no other authorized solutions remain available [36]. Valuable clinical experience can be gained, but the type of clinical data generated under the HE scheme fails to match clinical trial data and is not appropriate for supporting future marketing authorization applications (MAA). Despite broad ethical risk–benet assessment and informed consent from the patient before treatment [32, 159], an analysis of HE implemen­tation across seven countries revealed differences in HE interpretation and implementation. Although some countries required full compli­ance with good manufacturing practice, as well as non-clinical and clinical evidence, others did not [59]. Restricted scale HE treatment may apparently introduce parallel ATMP systems, dif-