There is currently much debate about adaptive pathways for new medicinal products to come to the market. The terms ’staggered approval’, ’progressive licensing’, and ’adaptive licensing’ have been used, often interchangeably, to describe the same broad concept. More recently, the term ‘Medicines Adaptive Pathways’ (MAPs) or ‘Medicines Adaptive Pathways to Patients’ (MAPPs) is discussed as potentially more appropriate terminology. For the time being, and in the interest of internal consistency, the term ’adaptive licensing’ (AL) is used throughout this document.
AL can be defined as a prospectively planned, adaptive approach to bringing drugs to market. Starting from an authorised indication (most likely a “niche” indication) for a given drug, through iterative phases of evidence gathering and progressive licensing adaptations concerning both the authorised indication and the potential further therapeutic uses of the drug concerned AL seeks to maximize the positive impact of new drugs on public health by balancing timely access for patients with the need to provide adequate evolving information on benefits and harms.
In addressing the ‘evidence versus access’ balance, and consistent with a staged approach to collection of evidence and consequent licence adaptations, AL aims at a life-cycle approach to evaluation and licensing of medicines.
AL uses the regulatory processes within the existing EU legal framework, including scientific advice (with participation of HTA bodies and/or payers and/or other stakeholders), centralised compassionate use, the “standard” marketing authorisation, conditional marketing authorisation, marketing authorisation under exceptional circumstances, risk management plans, other provisions of the pharmacovigilance legislation, patient registries, etc.
The Agency is aware that representatives from different stakeholder groups, including patients, academicians, research-based industry, HTA experts, and regulators from several jurisdictions have expressed an interest in exploring how the concepts of AL could be further explored and developed.
The potential benefits and risks of AL, as well as the issues that need to be addressed have been discussed in publications and at international conferences. Retrospective and hypothetical case studies have been developed by external groups to clarify the understanding of AL pathways.
The purpose of the pilot on AL is to provide a framework for informal interactions: by discussing ‘live assets’, i.e. medicines currently under development, it is hoped that all stakeholders will be able to address a range of technical and scientific questions (outlined in Annex I) which will help refine their understanding of how future AL pathways might be designed for different products and indications, what might be achieved by AL, how best to address the potential blocking factors and, possibly, to identify additional hurdles or issues that may not have become apparent yet.
Recalling that the aim of AL is timely access for patients to treatments that promise to address serious conditions where there is an unmet medical need, especially when there are no satisfactory alternative therapies, the Agency takes the view that all decision makers who ultimately determine patient access should ideally be involved in the pilot projects; this includes HTA bodies that inform reimbursement decisions and, where applicable, organisations issuing clinical treatment guidelines, and patient organisations. This is not intended to pre-empt current discussions with member states’ HTA bodies or with member states in the Pharmaceutical Committee coordinated by the European Commission but shall focus only on the technical and scientific issues of the ‘live asset’ under consideration. The examination of any legal aspects or potential legal limitations of AL within the existing EU legal framework is the competence of the European Commission who is carrying out this task in collaboration with the Member States and by consultation of relevant stakeholders, as necessary.
Giving due recognition to the fact that discussions on possible AL pathways of a live asset are of an exploratory nature, interactions between stakeholders will take place in a safe harbour environment so that strengths and weaknesses of all options for development, licensing and assessment may be explored openly and discussed without fear or favour in advance of more formal interactions that might eventually be undertaken such as Scientific Advice / Protocol Assistance or Marketing Authorisation Application; this is to ensure that none of the stakeholders represented at the table will be asked to make binding commitments or suffer unforeseen consequences.