A recent decision by the Italian Council of State (CS) comes as welcome news for the innovative pharmaceutical industry as it sets important boundaries to the initiatives that regional authorities can take in the attempt to limit public pharmaceutical expenditure under the increasing pressure of their budgetary constraints.

The CS has firmly stated that the national Italian Medicines Agency (AIFA) has exclusive competence in pharmaceutical regulatory policy concerning marketing authorisations, assessment of therapeutic indications, therapeutic equivalence between active substances, and pricing and reimbursement determinations, among other things. Therefore, no diverging recommendations can be taken by individual Italian regions concerning the use of medicines, as such independent actions would jeopardise the provision of uniform healthcare services across the country and undermine patients’ rights.

Facts

In 2015, the Veneto Region adopted a series of “evidence based recommendations” relating to the use of certain oncology medicinal products. Recommendations No. 1 and No. 3 (the Recommendations) concerned Roche’s Avastin and Perjeta, respectively, for the treatment of ovarian and other female reproductive system cancer (Avastin) and breast cancer (Perjeta).

The Recommendations were prepared by an ad-hoc Working Group set up by regional law and had the purpose of classifying the concerned oncology products under one of four categories, reflecting their level of “recommendation” in relation to specific indications and/or patient populations. For each category, the Recommendations set an expected percentage of use of the concerned product – the decree enacting the Recommendations establishing a monitoring system at the regional level to ensure compliance with such targets. The four categories are:

  • Recommended: “usable in the majority of patients” – expected use 60% or more;
  • Moderately recommended: “raising doubts about whether the medicine should be used in the majority of patients, but advising that its use should be taken into account” – expected use 30-40%;
  • Recommended in selected cases: “usable only in selected patient cases” – expected use 10-30%;
  • Not recommended: “advising not to use the product” – expected use less than 10%.

The Recommendations were formulated on the basis of a combination of the following four criteria (importantly: a mixture of scientific and economic considerations):

  1. Therapeutic alternatives;
  2. Quality of the scientific evidence;
  3. Risk/benefit ratio;
  4. Cost compared to therapeutic alternatives.

The Recommendations classified Avastin as either “moderately recommended” (for high-risk patients) or “not recommended” (for low-risk patients), and Perjeta as “moderately recommended” or “not recommended” for certain indications or patient populations.

Roche sought the annulment of the aforementioned Recommendations before the Veneto administrative court and, upon dismissal, appealed to the Italian CS.

Holding

The Italian CS stated that only AIFA is competent to make determinations regarding the marketing authorisation of medicinal products, the classification of medicines (e.g., medicines for hospital use), therapeutic indications, therapeutic equivalence between active substances, pricing, reimbursement and post-market monitoring of the use of medicinal products in Italy.

The CS reached this conclusion on the basis of a consolidated line of case law of both the administrative courts and the Italian Constitutional Court, specifying that pharmaceutical regulation reserves the aforementioned assessments to the national authority (AIFA). The Italian regions are prevented from regulating the use and reimbursement of medicines in a manner that is incompatible with the one established on the basis of AIFA’s recommendations at the national level.

More specifically, medicinal products classified by AIFA as “for hospital use” (Class H), such as Avastin and Perjeta, are part of the offering by the Italian National Health Service, and of the so-called “essential levels of healthcare” (livelli essenziali di assistenza) that must be guaranteed uniformly to all patients throughout the country. The CS found that Italian regions may not set stricter criteria for the supply of such products than those set by AIFA at national level, as such limitations would harm the uniformity of the “essential levels of healthcare” in Italy.

The CS put forward the following main arguments in support of its determination, finding that the Recommendations:

  1. Interfered, by producing independent technical evaluations at the regional level, with the technical assessments performed by AIFA at the national level (or, to the applicable extent for centrally authorised products, the EMA);
  2. Established therapeutic equivalence between active substances without having consulted AIFA, despite the latter being an exclusive competence of the medicine regulatory authority;
  3. Influenced the prescription of medicinal products by doctors, thereby limiting their freedom to prescribe in accordance with their clinical evaluations;
  4. Influenced the decision-making of hospital managers, thereby indirectly restricting doctor’s freedom of prescription;
  5. Negatively affected the uniform supply of the products in the Italian territory.

The CS therefore found that the Recommendations were unlawful and ordered their annulment. Importantly, neither (i) the fact that the Recommendations were allegedly based on the scientific advice of reputable oncologists and experts following internationally recognised scientific standards, nor (ii) the CS’s acknowledgement that the Veneto Region may have been pursuing the “abstractly commendable aim” of limiting public pharmaceutical expenditure prevented the CS from reaching the aforementioned conclusions.

A welcome judgment

In a time of uncertainty around pharmaceutical reimbursement policy, where budget-constrained governments attempt to undermine the integrity of the medicines regulatory framework in multiple ways, this CS decision comes as a welcome reminder that the assessment of medicinal products is a matter of pharmaceutical law and the exclusive competence of medicine regulatory authorities – even in times of financial difficulties. No parallel system should be permitted that undermines the predictability and soundness of the pharmaceutical regulatory framework, in the primary interest of innovation and – most importantly – of patient safety and public health.