EU drug manufacturers call for ATMP regulation overhaul
Only two ATMP marketing authorisations have been approved since the 2007 regulation came into effect, with three applications under evaluation
The European Association for Bioindustries, EuropaBio, has called for a re-assessment of how the European Union (EU) advanced therapy medicinal products (ATMP) regulation is being implemented because of the slow development of these medicines.
In response to a call from the European Commission for comments on the issue, the association said that the regulation ‘has not been sufficient to result in a surge of newly-approved ATMPs in the five years since it entered into force’. Indeed, only two ATMP marketing authorisations have been approved since the 2007 regulation came into effect, with three applications under evaluation. This is in spite of growth in the number of companies and investment in advanced medicines.
EuropaBio says part of the problem has been ‘some hurdles lying with the adequacy of the regulatory framework’. The association said the regulation ‘has been divergently implemented at European and EU member states level and between member states themselves’, cutting against the point of an EU regulation which is supposed to guarantee regulatory uniformity.
‘This is also exemplified by the very diverse implementation of the [EU] cells and tissue Directive across Europe,’ said the association.
As a result ‘further streamlining and clarifying’ of EU advanced medicine development rules would ‘greatly benefit any developer’. That said, the association does not want more harmonisation to mean excessive red tape, making regulatory compliance a ‘resource-consuming activity for SMEs. Therefore, it should not divert resources from innovation’.
The association said new guidelines should ‘always be aligned and specific’ and ‘take the latest scientific advances into account’.
Further streamlining and clarifying of EU advanced medicine development rules would greatly benefit any developer
A particular problem highlighted by EuropaBio is the way the regulation allows hospitals to treat patients with ATMPs ‘on a non-routine basis according to specific quality standards, and used within the same member state in a hospital under the exclusive professional responsibility of a medical practitioner, [under] an individual medical prescription for a custom-made product for an individual patient’.
While this sounds sensible, it has driven a ‘coach and horses’ through regulatory harmonisation, said EuropaBio. Some member states have implemented a rule on this so-called ‘hospital exemption’ or ‘HE’, while others ‘have used different definitions for the use of ‘non-routine’, and some have not defined it at all. As a result, ‘there are major irregularities in the national implementation of HE’, concluded the association, calling on the European Commission to ‘further clarify and strengthen the definition of hospital exemption’.
The key is ensuring that these special treatments should only be given when there are no approved advanced medicines for a particular health problem or it is impossible for a hospital to be involved in a clinical trial of a relevant drug under development, said the association.
Meanwhile, EuropaBio called for a review and clarification of how the advanced medicine regulation interacts with the cells and tissue directive, and of whether this directive should be turned into an EU regulation to maximise harmonisation across all member states.
The ATMP regulation has partly turned out to be an overly rigid corset which does not drive forward development and technical progress
The need for EU legislation on the issue to allow controls to take account of fast moving technological progress was stressed by the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) in its comments to the Commission. It said that the regulation set established a market approval system that was too onerous for the smaller companies and university facilities that currently dominate the European advanced medicine field, and who have ‘limited resources both financially and regarding staff’.
And while the ATMP regulation has provided a ‘better definition and a regulatory framework’ for advanced medicine development, it has also ‘partly turned out to be an overly rigid corset which does not drive forward development and technical progress for ATMP but hampers them’, said EUCOPE.
Indeed it stressed that the ‘rigidity of the legislation currently perturbs innovation in the ATMP field because technical improvements – which are achieved in fast succession for tissue engineered products and somatic cell therapeutic products – are counteracted by the rigid system of variations and line extensions’ within the market approval systems.
Another industry group, the Alliance for Advanced Therapies, also stressed the need for clarifying the technical requirements of market approval applications, so that the data requirements are not excessive. It wants medicine developers to be given a break, given ‘the limited marketing authorisation experience so far, the diversity of ATMPs and the rapid[ity of] state-of-the art developments’.
The alliance suggested the regulation’s risk-based approach (RBA) principles should be applied proactively ‘to help bring proportionality to the amount of data to be generated’.