Regulation of advanced therapy medicinal products in Europe and the role of academia

Abstract

GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field.

About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use

“…QPs are approved by the regulatory authority and often have a pharmaceutical background. An issue identified by Pearce et al [22] and also observed by us [57] is the hesitation of QPs to take over responsibility for releasing an ATMP, as such products may not be part of their area of expertise. While we are in the comfortable situation that denovoDerm and denovoSkin products are manufactured in a certified GMP facility in Zurich [58] including release by a QP, difficulties were encountered when arranging import of the ATMPs to The Netherlands for an international multicenter clinical trial.…”

“…Interestingly, a survey at European research centers working with ATMPs showed that most of the participating centers supported strict and careful ATMP regulation. None of the centers in this survey supported potential lower GMP standards for ATMPs than standard medicines or lower standards for academic groups [22]. …”

“…As also shown by Pearce et al [22], this leads to the use of far-fetched animal models [51]. To perform pre-clinical testing on ATMPs, animal testing is standard, though the choice of the appropriate small and large animal model is challenging.…”

“…al. [22] therefore suggests a paradigm shift in pre-clinical ATMP testing, suggesting first-in-man data to be used as part of the dossier for clinical trial authorization. Such first-in-man data, also referred to as phase 0 study, then might be followed by a classic phase I trial.…”

Natural Killer Cells for Therapy of Leukemia

“…However, high operational expenditures for such facilities need to be taken into account [86]. Marketing of such ‘advanced medicinal products', is a complex process which in Europe is overseen by the European Medicines Agency [85,88]. Hence, practicability and cost factors pose limits to the implementation of such new types of personalized medicines in blood centers.…”