Insights

On July 12, 2025, the Italian Medicines Agency (AIFA) published updated criteria in the Official Gazette for the classification of innovative drugs and of antimicrobial agents used in infections caused by multidrug-resistant organisms (MDROs).

🔍 Key Elements of Therapeutic Innovation

The therapeutic innovation of a drug is assessed taking into consideration:

• production technology of the active ingredient,
• mechanism of action,
• method of administration,
• clinical efficacy and safety,
• impact on quality of life,
• implications for the healthcare system organisation.

✅ Eligibility Criteria

Therapeutic innovation may be recognized when the medicinal product:

• Targets serious diseases or conditions with potentially fatal outcomes, repeated hospitalizations, progressive disability, or major quality-of-life impacts;
• Addresses conditions with a medium to low epidemiological burden;
• Demonstrates the ability to cure the disease or reduce life-threatening complications or slow disease progression or improve the quality of life of patients in terms of functional independence and pain-related outcomes, in the specific case of rare and ultra-rare diseases.

❌ Exclusion Criteria

A medicinal product is not eligible to Innovation status if:

• it is based on off-patent or never patented active substances;
• the negotiation request has been submitted to AIFA for a new therapeutic indication more than ten years after the date on which the first therapeutic indication was granted innovation;
• it is an anti-infective agent classified as ‘Reserve’ in WHO’s AWaRe classification or active against WHO-listed priority pathogens (subject to a different reimbursement path).

📊 Innovation Assessment Criteria

Recognition of innovation is based on a multidimensional evaluation, using predefined scoring levels across three domains:

1. Therapeutic Need

The therapeutic need is measured using a 5-level scale (Maximum, Important, Moderate, Minor, Absent) based on efficacy, safety, and clinical relevance of existing therapeutic options.

Therapeutic options that can be considered for the assessment include:

• 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.

2. Added Therapeutic Advantage

The Added Therapeutic Advantage is determined by the clinical benefit of the product on outcomes recognised as clinically relevant and validated for the specific disease in comparison to existing treatments and is assessed using a 6-level scale (Maximum, Important, Moderate, Minor, Absent, Not assessable).

The comparison could be based on the results of direct comparative clinical trials or of indirect comparisons performed using appropriate statistical methods.

Patient-Reported Outcomes Measures (PROMs) and Patient-Reported Experiences Measures (PREMs) will be taken into account, if available and validated, only if they can demonstrate a significant improvement in quality of life.

3. Quality of Evidence

Quality of Evidence is measured using the GRADE methodology on a 4-level scale (High, Moderate, Low, Very Low) and supports the methodological consistency and generalisability of the efficacy and safety evidence of the medicinal product to the clinical practice.

🧾 Process and Benefits

• Innovation status is granted when all three criteria score at least "Moderate". The new guidelines no longer distinguish between conditional innovations and full innovations.
• For rare/ultra-rare conditions, a “Low” quality of evidence is acceptable.
• Innovation status is valid for 36 months (non-renewable).
• A new product in the same class (same mechanism of action) may qualify under “class innovation” for the remaining period of the original recognition.

• All innovative products are subject to monitoring via the AIFA registry, limited to the approved innovative indication.

• Benefits of Innovation Status:
  • Access to the Innovative Medicines Fund.
  • Exemption from mandatory price reductions (5% + 5%).
  • Facilitated entry into Regional Formularies.
  • Exclusion from the calculation of the total amount of pharmaceutical expenditure for direct purchases.

🦠 Management of Antimicrobial Agents against MDROs

For anti-infective agents classified as 'Reserve' under WHO’s AWaRe framework or targeting WHO-priority pathogens, AIFA provides a dedicated access route that does not involve innovation assessment but still allows for funding and reimbursement under defined conditions.

✅ Inclusion Criteria

• the product is included in the WHO “AWARE” list and classified as 'reserve' or active against pathogens contained in the WHO "Bacterial Priority Pathogens List";
• the use is limited to the treatment of diseases caused by multi-resistant germs;
• the medicinal product is subject to patent coverage and/or regulatory data protection.

❌ Exclusion Criteria

• Products not reimbursed by the Italian NHS;
• Applications submitted after patent or exclusivity expiration;
• Use outside of MDRO-related indications.

Benefits:

• Access to a dedicated annual fund of €100 million per year, until the expiry of patent protection or regulatory data protection
• Exclusion from the calculation of the total amount of pharmaceutical expenditure for direct purchases.

These products are subject to monitoring of dispensing through the AIFA monitoring register.

💼 RPN: Your Strategic Partner in Pricing & Reimbursement and Market Access

Navigating the evolving regulatory and market access landscape requires experience, precision, and strategic insight.

At Regulatory Pharma Net (RPN), we provide integrated support for pharmaceutical and biotech companies in:

• Developing HTA strategies, especially under the new EU HTA Regulation.
• Preparing robust, evidence-aligned innovation dossiers;
• Managing Price & Reimbursement negotiations with AIFA.

With deep knowledge of the Italian system and European context, RPN ensures Companies have the best chance of gaining rapid and sustained access to market.

📩 To explore how RPN can support your next submission or product launch, contact us at info@rpngroup.com .