AIFA new era: What we’ve learned so far – and what’s next?

Fig.1 – Number of procedures processed by the CSE in each session (3-mo. rolling average). Source: Esiti CSE – Settore HTA, from Apr. 2024 to Jan. 2025.

An analysis of the distribution of procedure types across sessions shows the CSE likely prioritizing new indications and products in its early meetings, to then settle, in recent sessions, on a consistent distribution among the different procedure categories, with renegotiations typically making up the largest share, followed by indication extensions, new products, and orphan drugs (Fig.2).  

Fig.2 - Rolling averages of negotiation type (%) by grouped session. Source: Esiti CSE – Settore HTA, from Apr. 2024 to Jan. 2025.

In this analysis, to address the backlog of procedures caused by the AIFA assessment halt during the transition to the new CSE, a distinction has been made between procedures initiated under the former AIFA and those under the new CSE. To differentiate between them, a temporal cutoff was applied based on the "procedure duration" specified in the CSE outcome document: procedures that began before January 2024 (i.e., prior to the implementation of the new CSE) are categorized as initiated under the former AIFA. 

Overview of negotiation interactions between the CSE and manufacturers

As mentioned above, based on the new reform, the manufacturer would be allowed to formulate a maximum of two counteroffers. This reflects AIFA’s commitment to streamlining negotiations while simultaneously addressing the backlog of procedures initiated under the former AIFA. However, it is important to remember that manufacturers can also engage with AIFA through scoping meetings, which are not tracked in the analysis (as they are not included in the publicly available AIFA agendas).

Breaking down the visible interactions already completed and still ongoing between the CSE and manufacturers, we see that the CSE has largely adhered to this two-interaction limit, with the vast majority of procedures (90%) requiring only one or two interactions so far (59% with a single interaction, and 31% with two interactions) (Fig.3).

Approximately 10% of all procedures have instead exceeded this threshold, requiring three interactions or in a few cases even more. Among the procedures requiring more than two interactions, renegotiations accounted for a significant portion (42%), followed by new chemical entities (27%), orphan drugs (12%), and indication extensions (9%).  Extended discussions appear in general more common for high-impact therapies such as oncology drugs and ATMPs, suggesting a pragmatic approach that balances procedural streamlining with the complexities of innovative treatments.

However, since procedures started with the former AIFA could have had interactions with the previous committees (not mapped here), a more precise analysis would need to focus only on procedures started with the CSE, the majority required only a single interaction, while no cases with more than two interactions were observed. On the other hand, an analysis of the ongoing procedures shows that five procedures have already had over two interactions, confirming some flexibility from the CSE (Fig.3). 

Fig.3 - Procedures by number of interactions with AIFA. Source: Esiti CSE – Settore HTA, from Apr. 2024 to Jan. 2025.

To count negotiation interactions, we have considered the CSE opinions (i.e., “Parere espresso dalla CSE”) mentioned in monthly agendas and outcomes (i.e., “Esiti CSE – Settore HTA”) published by AIFA from April 2024 to January 2025.

Negotiation timelines with the new CSE

The national P&R process in Italy is structured into three key phases: setup (from dossier submission to AIFA’s initiation of the procedure), CSE assessment, and from BoD approval to Official Gazette (OG) publication. This analysis focuses on the second phase only.

According to our analysis, the average duration of the CSE assessment for all the concluded procedures ranges from 11 to 13 months across key negotiation types (i.e., orphan drugs, indication extensions, re-negotiations, and new molecules) (Fig.4).

However, when excluding procedures initiated under the former AIFA, which likely experienced prolonged timelines due to the negotiation stop at the beginning of 2024, the average CSE assessment duration ranges between five and seven months under the new CSE framework (Fig.4).

Factoring in the common time between dossier submission and procedure initiation of one month, as well as the 2-3 months typically required from BoD approval to the publication in the Official Gazette, the overall duration of the P&R process under the CSE is estimated to be 8 to 10 months, reflecting a positive trend toward greater efficiency.

It is important to note, however, that in some cases the publication in the OG can take longer vs. the timeline indicated above, potentially leading to a longer overall duration. 

Fig.4 – Duration of CSE assessment phase (i.e., it does not consider setup and time from BoD approval to the Official Gazette publication). Source: Esiti CSE – Settore HTA, from Apr. to Jan. 2025.

To analyze negotiation timing, we considered the period from the opening of the procedure to either the completion of the assessment or submission to the BoD. It is important to note that this timing does not account for the time between P&R dossier submission and procedure initiation, nor the time between BoD approval and the Official Gazette publication.  

Innovative drugs under the new CSE

Under AIFA’s new structure, the CSE assesses the innovation status in parallel with the price negotiation, provided the manufacturer has submitted an innovation application. This differs from the previous system, where the CTS assessed a drug’s innovation status before the negotiation with the CPR.

As of February 2025, among procedures assessed by the CSE, innovation assessments outcomes have been published for five products, with only three products receiving a positive evaluation:

• Full innovation status was granted to only one product (orphan drug, metabolic disorders). 
   
• Conditional innovation was granted to two products (orphan drugs, oncology space). 
   
• Three products were deemed not innovative. 
   

Key takeaways from the analysis

In conclusion, following AIFA's new organizational structure it has been observed that:

• The CSE has been progressively enhancing the efficiency of the assessment process, as seen in the increasing number of procedures assessed per session. 
   
• The increased process efficiency is also reflected in the timelines, with an average CSE assessment duration of approximately 5-7 months (It does not consider setup and time from BoD approval to the Official Gazette publication).
   
• There is a general tendency to adhere to the limit of two negotiation interactions with the manufacturer, as per regulation, though exceptions exist reflecting CSE flexibility. 
   
• Among the procedures initiated under the CSE, innovation status has so far been granted exclusively to orphan drugs. However, given the limited number of assessments, it remains premature to draw definitive conclusions on the CSE approach. 
   

2025 Italian Budget Law

Another significant recent change, though separate from AIFA’s reorganization, comes with the 2025 Italian Budget Law, which introduces key measures impacting drug negotiations, particularly the innovation status.

• Access to the innovation fund has also been updated. Until 2024, a single €1.3 billion fund was available exclusively for drugs granted full innovation status. With the new Budget Law, provided that a monitoring registry is in place, drugs with conditional innovation status and reserve antibiotics can also access the fund. Starting from January 2025 the €1.3 billion fund will be allocated as follows: €900 million for fully innovative drugs, €300 million for products that achieved a conditional innovation status, and €100 million for reserve antibiotics. The inclusion of conditional innovative drugs in the fund represents a significant shift, however the split of the innovation fund may evolve in the coming years, in light of the revision of the innovation algorithm and the experience gained over time. 
   
• Indication expansions submitted more than 10 years after the first achievement of an innovation status (for a different indication of the same product) will no longer be eligible for innovative funding. 
   

Beyond these changes, the 2025 Budget Law has also laid down the groundwork to broaden the criteria for assessing innovation, mentioning factors such as drug technology (e.g., biologics, CAR-Ts), mechanism of action, benefits to the healthcare system, and improvements in patient quality of life. These additions signal a shift toward a more holistic evaluation framework, making these factors increasingly relevant in pricing and reimbursement decisions.

Key uncertainties and next steps

Following AIFA’s restructuring, several key uncertainties remain regarding the implementation of new processes and their long-term impact on pricing and reimbursement in Italy:

• Impact of the EU JCA report: Uncertainty remains on how the EU JCA report will be integrated into AIFA’s processes, as national guidelines are yet to be defined. 
   
• Evolving role of cost-effectiveness analysis (CEA): CEA is gaining importance but its influence on negotiation outcomes varies depending on the context, being particularly relevant for new launches (with more flexibility expected for orphan products).   
   
• New criteria for innovation status assessment: The 2025 Budget Law emphasizes that innovation status will be prioritized for curative therapies, treatments for multidrug-resistant infections, and therapies that reduce mortality risks or improve quality of life, particularly in rare diseases. However, the new criteria for the innovation assessment are yet to be updated and expected to be published in the coming months. 
   

For manufacturers, these uncertainties underscore the growing need to craft compelling, tailored value propositions for the Italian market. Beyond demonstrating efficacy and safety, companies must anticipate objections and refine narratives to meet the evolving expectations of the CSE within the constraints of limited interactions. 

This analysis is based exclusively on publicly available information. Due to data limitations, certain assumptions were necessary, including the application of a cutoff on submission timelines to address gaps in the available records. Additionally, some inconsistencies in publicly released documents may have had a minor impact on the outcomes of this analysis. As the Italian P&MA landscape continue to evolve, further analyses are required to fully evaluate the impact of the anticipated changes on drugs negotiation and the approval process. 

Thanks to contributions from Dario Iodice, Andrea Vandarini and Eleonora Merli!