“The framework agreement, accompanied by assessments based on Hta (Health technology assessment), appears to be the best method in order to guarantee uniform access to the best therapies for patients with a view to vertical equity, sustainability, appropriateness, clinical need and protection of competition. However, it is necessary that it be used more uniformly in the Italian Regions. In a framework agreement where both the originator and the biosimilar are maintained, even if the originator maintains a minority share of the market, the clinician is allowed to have the originator available if the individual case requires it “. Thus Francesco Saverio Mennini, Director of the EeHta del Ceis Center, Faculty of Economics, University of Rome Tor Vergata, SiHta president, speaking today during the press conference for the presentation of the Expert opinion ‘Therapeutic Equivalence: Regulatory / Legal Review, Structural Approaches & new alternative procedural models’, organized by Mapcom Consulting, with the unconditional contribution of Gilead Sciences and Sanofi Italia.
“Decisions – observes Mennini – must therefore be taken on the basis of an assessment based on HTA including economic evaluations (cost effectiveness, minimization of costs, etc …) tending to underline the value of a technology.” In addition, thanks to HTA “The decision maker can make a more complete and exhaustive evaluation – he continues -: the method, in fact, allows to obtain a better demonstration of the value of the drug and its functionality with respect to a specific patient”. In this regard, “a recent study by the Ceis of Tor Vergata – he reports – highlighted how, in light of the current regulatory framework and with reference to biosimilars, the possibility of resorting to the framework agreement guarantees a statistically significant reduction in the price differential between originator and biosimilar, with a potential cost containment effect, also protecting competition and clinical needs “.
From a scientific point of view, “three types of equivalence can be identified: pharmaceutical, therapeutic and in clinical practice” states, in her speech, Paola Minghetti, full professor in the disciplinary group Pharmaceutical Technological Application, Department of Pharmaceutical Sciences of the University from Milan. “In particular – he specifies – therapeutic equivalence can be established both for medicines containing the same active ingredient (generics and biosimilars) and for products containing different active ingredients but with the same therapeutic indication. In the event that the active principle is represented by a biological substance – continues Minghetti – the therapeutic equivalence is subject to the carrying out of the comparability exercise which consists of comparative studies conducted also for the preclinical and clinical aspects “.
“The most complex case concerns the determination of the therapeutic equivalence between different active ingredients but having the same therapeutic indication and belonging to the same chemical class (Atc classification beyond the fourth level). These medicines – underlines Minghetti – can have comparable efficacy, but in the pre-authorization process no comparative studies were carried out to prove it.The regulatory agency must then find other sources of information to understand if this equivalence exists and find data and information that are not present in the registration files.
According to experts, the Italian discipline on the subject of therapeutic equivalence has a clear anomaly, especially as regards the methods of balancing the principles of health protection and the good performance of public administration, in particular in the form of containing public spending. “Today a regulatory revision would be desirable also because in fact there is no definition of therapeutic equivalence nor an exact indication, in an act having the force of law, of the criteria on the basis of which it is determined”, explains Vincenzo Salvatore, focus Healthcare and Life sciences team leader, BonelliErede, Full Professor of European Union Law, Insubria University, Varese. “I am convinced that, beyond a regulatory intervention that establishes some objectively appreciable criteria that must guide the exercise of therapeutic equivalence evaluation – he argues – if we want to introduce a cost containment mechanism it is perhaps not through an equivalence evaluation therapeutic, but perhaps in application of more modern criteria that led, for example, the European Union to adopt the recent regulation on Health technology assessment ”.
“The ten years that have passed since the issuance of Legislative Decree 95 of 2012 – adds Salvatore – allow us to highlight a series of critical profiles, both as regards the automatic substitutability between equivalent drugs (think of the complexity of the relationship between biologics and biosimilars) and as regards the reading, sometimes questionable, that the notion of therapeutic equivalence has been given by the administrative jurisprudence of legitimacy, think of the affirmation of the therapeutic equivalence of drugs that have the same fifth level ATC code “. The evaluations” seem increasingly oriented towards the pursuit of cost containment purposes, risking to overshadow scientific evaluations – the lawyer points out -. Keeping scientific assessments separate from those of an economic nature – as is the case for the European Medicines Agency – represents an element of guarantee and objectivity which, perhaps, also in Italy requires a rethinking of the system ”. Finally, “the subjects who have to make scientific evaluations and the subjects who carry out economic evaluations – concludes Salvatore – must be kept separate. They can talk and dialogue, but mixing the two skills risks polluting them both “.