Insights

The Italian Medicines Agency (AIFA) has published the long-awaited update to the guidelines for preparing the price and reimbursement dossier. The new version, released on 23^rd December 2025, includes some important updates in both structure and substance, aligning the Italian process with the latest European standards and the Health Technology Assessment (HTA) framework.

Regulatory background

The guidelines have been updated to take into account:

• Regulation (EU) 2021/2282 of the European Parliament and of the Council of December 15, 2021, on Health Technology Assessment, as well as the relevant Implementing Acts adopted by the European Commission and the technical and procedural guidelines adopted by the HTA Coordination Group.
• The changes made pursuant to Decree-Law No. 169 of November 8, 2022, coordinated with Conversion Law No. 196 of December 16, 2022 (Official Journal - General Series - No. 301 of December 27, 2022) which abolished the Technical-Scientific Commission (CTS) and the Pricing and Reimbursement Committee (CPR), assigning their functions to the Scientific and Economic Commission for Medicines (CSE).
• The changes made by Resolution No. Pres/966/2025, in which AIFA identified the criteria for the classification of innovative drugs and antimicrobial agents used in infections caused by multidrug-resistant organisms

Expanded Scope of Comparators

Comparators are identified within the following:

• the Best Standard of Care (any other pharmacological or surgical treatment or variable combination of treatments, including any medical devices or digital therapies, which constitute the best treatment available in healthcare pathways),
• medicinal products with a comparable therapeutic indication (i.e. medicinal products that share the same authorised therapeutic indication or the same reimbursed therapeutic indication)
• the comparative treatment used in the registration clinical trials.

New Criteria for Therapeutic Innovation

The new guidelines incorporate the recently introduced (12^th July 2025) changes to the criteria for the assessment of therapeutic innovation (see RPN blog here).

Description of Clinical Evidence

• Companies have the possibility to provide indirect comparisons and network meta-analyses,
• Greater emphasis is put on patient-reported outcomes (PROMs) and experience measures (PREMs), which must be validated
• The description of clinical trials becomes optional for drugs that underwent Joint Clinical Assessment

Economic Evaluations

• A Budget Impact Analysis (BIA) for new drugs or extensions of indications is requested if at least one of following occurs:
  • the expected turnover for the first 3 years of reimbursement is equal to or greater than €50 million;
  • the estimated expenditure for the purchase of the Product is significantly offset (i.e., by at least 30%) by lower expenditure on other drugs and/or other healthcare resources.
• Cost-Effectiveness/Cost-Utility Analyses (CEA/CUA) are mandatory only for new drugs (including orphan drugs) or extensions of indications. However, in case of extensions of indications, economic analyses are not mandatory in the following cases:
  • the extension of the indication concerns subgroups of patients of an indication already reimbursed (e.g., extension to pediatric population, modification of reimbursement criteria, etc.);
  • the weight of the new indication on the total turnover of the drug is less than 15% in each of the first 3 years.
• In case the available evidence shows equivalence or non-inferiority of the Product vs the Comparator or non-statistically significant differences in clinically relevant outcomes, it is possible to submit a cost-minimisation analysis.
• Models must be submitted as Excel or TreeAge files, with the possibility to also provide models generated through “R” (in addition to the “standard” formats)

Implementation

The new guidelines for P&R dossiers will become operational on 1^st April 2026 in order to provide pharmaceutical companies with a reasonable period of time to adapt to the new requirements.

Conclusions

The 2025 AIFA guidelines represent a decisive step forward for the Italian pharmaceutical market. By embracing HTA principles and European harmonization, they set a new standard for price and reimbursement.

At RPN, we understand that navigating the Italian landscape can be complex and resource-intensive. Our team of market access and regulatory experts is ready to support pharmaceutical companies at every stage of the dossier preparation process—from strategic planning to the submission of robust, compliant, and value-driven dossiers. With our deep knowledge of the Italian and European regulatory landscape, we help you anticipate challenges, optimize your submissions, and accelerate patient access to innovation.

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