In March 2021 the Italian Medicines Agency adopted new guidelines for drug pricing and reimbursement decisions.
The Italian Medicines Agency (Agenzia Italiana del Farmaco – “AIFA”) is the national authority vested with jurisdiction over medicinal products. The Italian legislative Decree 219/2006 on medicinal products for human use (“Italian Medicines Code”), implementing Directive 2001/83/EC, and Regulation (EC) 726/2004 sets forth the main regulatory framework for the authorization of medicinal products in Italy.
AIFA and its technical and advisory committees (CTS – Technical Scientific Committee and CPR – Pricing & Reimbursement Committee) are responsible for defining the system of eligibility for reimbursement and supply for all authorized medicinal products, as well as negotiating the price of those to be paid by the National Health Service (NHS – Servizio Sanitario Italiano [SSN]), after negotiation with pharmaceutical companies.
The pricing process
With Resolution no. 1372/2020, AIFA has adopted the consolidated version of the new “Guidelines for drafting the dossier supporting the pricing and reimbursement application for medicinal products” according to the Ministerial Decree on 1 August 2019 (published in the Italian Official Journal no. 185 of 24 July 2020).[i] The new legislation has been enacted to answer the need to introduce criteria adequate to the continuous evolution of drug policies and to meet higher standards of transparency. In particular, the Decree substitutes the historic Resolution 3/2001 by the Inter-ministerial for Economic Programming Committee (CIPE),[ii] and defines the criteria and the ways in which the Italian Agency of Medication (AIFA) determines, the price of drugs reimbursed by the National Health Service.
Differences between the two AIFA resolutions for the pricing and reimbursement procedure
Compared to the CIPE Resolution, the Decree introduces relevant changes, shown in this table (PDF).
First, the new rules will apply to a broader range of products, including medicinal products authorized through centralized, mutual recognition, decentralized and national procedures, medicinal products to be included in the law 648/1996 (early access program)[i] and some C/C(nn) medicinal products purchased by NHS facilities for public health needs.[ii]
Second, the Decree focuses on the added therapeutic value of medicinal products versus the main comparators rather than to the favourable cost-effectiveness ratio as of CIPE Resolution. This represents one of the most important changes, as the company will have to provide evidence on the drug clinical benefit with respect to available alternatives (or best supportive care in case these are not present). Furthermore, with the scientific documentation presented in support of the negotiation request, the company will have to provide self-certified information on the:
- Clear identification of the comparator(s) or, where not available, of the best supportive care, including, if relevant, any non-pharmacological therapeutic strategy to demonstrate the added value of the drug over therapeutic alternatives in terms of clinical outcomes and costs
- Tools, including diagnostic, to identify eligible patients, and the type and level of care envisaged for the product administration
- Prices of the product in other EU countries and UK with info on negotiated discounts and/or managed entry agreements and/or any confidentiality agreements
- Details on the product patent status
- Production capacity as well as ability to manage unexpected manufacturing issues
- Mechanisms envisaged to ensure adequate supply of the drug to the NHS, avoiding situations of shortage
- Any public contributions/incentives received for R&D activities.
A further change is that the Budget Impact Analyses (BIA) and pharmaco-economic analyses are now mandatory. Companies may present the following types of analysis:
- BIA from the NHS perspective to provide forecast of expenditure on pharma and other healthcare costs highlighting potential saving effects due to the new drug (time horizon of at least 2 years)
- Cost effectiveness analysis and/or cost utility conducted in comparison with the standard of care identified within the Italian NHS context with a preferred lifetime time horizon, and also with incremental costs and outcomes presented at five and ten years.
AIFA recommends that companies refer to the CHEERS Checklist and to the principles of good practice relating to the development of budget impact analyses, as published by ISPOR.[i]
Regarding the negotiation procedure, while the CIPE Resolution expected this to be activated only by the pharmaceutical company, the Decree also guarantees this capability to AIFA. Specifically, this will be possible for drugs: 1) with significant impact in terms on NHS expenditure or inappropriate prescribing due to market changes which lead to an excessive increase in its use or to an unfavorable cost/therapy ratio compared to other reimbursed drugs; 2) that have never undergone previous negotiation; 3) not reimbursed due to failure in reaching a price agreement in a previous negotiation. Furthermore, while with the CIPE Resolution the negotiation procedure had to be completed within 90 days, the new one Decree provides for a term of about 180 days, which can be interrupted only once if AIFA requests an integration of additional evidence.
The Technical-Scientific Committee (CTS) will evaluate the clinical and the therapeutic added value of the drug versus clearly identified comparators may, if necessary, call a scoping meeting, when appropriate, between AIFA and the company following the submission of the dossier will be called. The Pricing and Reimbursement Committee (CPR) will evaluate the reimbursement price on the basis of the added therapeutic value of the applicant drug (according to CTS decision). Should the drug not demonstrate superiority vs the comparators and the company does not provide a price counteroffer (same or even lower price than identified comparators), the negotiation will have a negative conclusion.
To simplify negotiation procedures, the Decree introduces the possibility for AIFA to regulate automatic mechanisms in favour of generic and biosimilar drugs.
Finally, similarly to the CIPE resolution, the contract between AIFA and the manufacturer is automatically renewed every 24 months, unless AIFA or the company do not propose an alteration of the conditions within 60 days from the contract expiry date (instead of previously 90 days). , for example in case the company demonstrates objective difficulties in obtaining raw materials or incurs in demonstrated increased manufacturing costs.
The new guidelines became effective on 1 March 2021. An online price negotiation system is in place that allows companies to submit the documentation for the pricing and reimbursement procedure for medicinal products and to monitor the progress of the various stages of the negotiation procedure. A new electronic interface is being developed by AIFA to allow the preparation and online filing of the Dossier.
At ICON, we are ready to support pharmaceutical companies providing a full range of services, from strategic analysis, pricing strategy, development of economic models, drafting of the pricing and reimbursement application, per these new requirements, submission and follow-up of the procedure, including attendance to negotiation meetings with the Italian Authorities.
To learn more, visit ICONplc.com/HEOR or contact us today.
 Determinazione DR 1372-2020. https://www.aifa.gov.it/en/-/determinazione-dg-1372-2020-linee-guida-per-la-compilazione-del-dossier-a-supporto-della-domanda-di-rimborsabilita-e-prezzo-di-un-medicinale
 Deliberazione n.3/2001, Individuazione dei criteri per la contrattazione del prezzo dei farmaci, GU (Serie Generale n.73 del 28.03.2001)
 Legge 23 dicembre 1996 n. 648, Conversione in legge del decreto-legge 21 ottobre 1996, n. 536, recante misure per il contenimento della spesa farmaceutica e la rideterminazione del tetto di spesa per l'anno 1996, GU Serie Generale n. 300 del 23.12.1996. https://www.parlamento.it/parlam/leggi/96648l.htm
 Legge 8 novembre 2012, n. 189, articolo 12, comma 5. G.U. n. 263 del 10/11/2012. Conversione in legge, con modificazioni, del decreto-legge 13 settembre 2012, n. 158, recante disposizioni urgenti per promuovere lo sviluppo del Paese mediante un piu' alto livello di tutela della salute. (12G0212) (GU Serie Generale n.263 del 10-11-2012 - Suppl. Ordinario n. 201). https://www.gazzettaufficiale.it/eli/id/2012/11/10/012G0212/sg
 Consolidated Health Economic Evaluation Reporting Standards (CHEERS) - Explanation and Elaboration. April, 2013. https://www.ispor.org/heor-resources/good-practices/article/consolidated-health-economic-evaluation-reporting-standards-(cheers)---explanation-and-elaboration.