With Resolution No. 966 of July 9, 2025, which replaces the previous Resolution No. 1535 of September 12, 2017, AIFA (Italian Medicines Agency) has redefined the evaluation criteria for the recognition of therapeutic innovation and for the management of antimicrobial agents for infections caused by multidrug-resistant organisms, implementing Article 1, paragraphs 281 and following, of Law No. 207/2024.

 The innovativeness of a medicinal product is assessed based on the technology used to produce its active ingredient, its mechanism of action, route of administration, clinical efficacy and safety, its impact on patients’ quality of life, and its implications for the healthcare system.

For this purpose, a drug is considered innovative depending on the efficacy and safety results compared to existing therapeutic alternatives listed in the national pharmaceutical formulary at the time of its introduction, within a specific therapeutic indication.

The recognition of innovative status is based on three main criteria:

1. Therapeutic need: determined by the lack of effective treatments for a specific disease or condition, or the inadequacy (in terms of efficacy/safety) of existing options.
2. Added therapeutic value: assessed based on the clinical benefit and its magnitude in terms of outcomes that are recognized as clinically relevant and validated for the specific condition. The overall benefit of the medicine under evaluation is compared to available alternatives (if any) within the National Pharmaceutical Formulary prior to its introduction. This evaluation is based on comparisons of efficacy and safety through direct comparative clinical trials or indirect comparisons with robust statistical methodologies.
3. Quality of evidence: high-quality evidence ensures the transferability of results obtained in pivotal clinical trials to real-world clinical practice.

For the first two criteria, a five-level rating scale is applied (maximum, significant, moderate, low, absent), while the third criterion is rated on four levels (high, moderate, low, very low).
Therapeutic innovation is granted when all three criteria reach at least a “moderate” level, except in the case of orphan drugs, where a “low” quality of evidence may be accepted.

Additionally, an added value may be recognized if the drug’s preclinical and clinical development has been predominantly carried out in Italy.

The recognition of innovative status is valid for a maximum of 36 months, without the possibility of extension. It entitles the product to access resources from the Innovative Medicines Fund; temporary exemption from statutory price reductions; inclusion in Regional Therapeutic Formularies (PTR); exclusion from the calculations of direct purchase pharmaceutical expenditure and market share thresholds attributed to the Marketing Authorization Holder (MAH).

 As for drugs targeting multidrug-resistant organisms, AIFA does not assess standard innovativeness for medicinal products based on active ingredients classified as “reserve” by the WHO or as active against priority pathogens on the Bacterial Priority Pathogens List. These products can access the Innovative Medicines Fund, up to an annual ceiling of €100 million, and until the expiration of patent protection or data exclusivity periods.

The resolution entered into force on July 13, 2025, the day following its publication in the Official Gazette.