The granting of the community marketing authorisation (MA) does not mean a medicinal product is simultaneously available throughout all the European countries. In fact, following the MA granting, some aspects like the Price and Reimbursement (P&R) and other mandatory country-specific activities should be accounted for before placing the product on the market.

However, for medicinal products without a valid therapeutic alternative, Member States can nationally define procedures to access them in advance.

In Italy, the options to access a medicinal product before the MA, are the following:

• Named Patient request for importation from a country where the medicinal product has already a MA
  The concerned clinician must fill in a request for importation (“Nulla Osta”). The packs imported shall not exceed the amount necessary for the treatment of 90 days. The medicinal product is paid by the hospital; only if it is requested for hospital use it can be reimbursed by the NHS.
• Request for inclusion in the list of drugs fully reimbursed by the National Health System (NHS)
  The medicinal products can be included in the 648/96 list on the proposal of the Technical Scientific Committee (CTS) of the Italian Medicines Agency (AIFA), associations of patients, scientific societies, universities or public/private hospitals. Specific eligibility criteria need to be met. The medicinal products included in the list are fully reimbursed by the NHS and all patients eligible for treatment can access the treatment.
• Named Patient request for access to the AIFA 5% fund
  A funding request on a named patient basis should be submitted by the Concerned Region on behalf of the Centre of Reference or directly by the Centre. Specific eligibility criteria need to be met. Generally, this is the preferred option when the number of patients eligible for the treatment  is very low. The treatment costs are reimbursed by AIFA.
• Compassionate use
  The named patient requests for compassionate use should be submitted by the physician to the concerned Ethics Committee and notified in parallel to AIFA. Specific eligibility criteria need to be met. Such requests are evaluated during routine EC meetings unless urgency is highlighted. In this context the drug must be provided free of charge by the company.

The applicability of the available options has to be evaluated on a case-by-case basis.

Introduction

The first Joint Clinical Assessment (JCA) under the EU HTA Regulation has now been published, marking the transition from a regulatory concept to an operational reality.

This inaugural report, focused on tovorafenib (OJEMDA) in paediatric low-grade glioma, provides the first tangible insight into how the EU HTA framework will perform in practice and what it will require from pharmaceutical companies.

Assessment overview

The assessment was structured around eight PICOs, reflecting the EU ambition to capture multiple clinical settings and comparators across Member States.

However, only one PICO could be meaningfully informed by comparative evidence, immediately highlighting the gap between available clinical data and HTA expectations.

Key findings

Most PICOs could not be assessed due to the absence of comparator data, limiting the ability to draw conclusions across relevant clinical scenarios.

Where comparative analysis was performed, it relied on unanchored indirect comparison methods (MAIC) applied to a single subpopulation, based on non-comparative clinical evidence.

Main limitations

The assessment is characterised by a high level of uncertainty, driven by small sample sizes, reliance on single-arm studies, and methodological constraints inherent to indirect comparisons.

In addition, the absence of overall survival data and the limited robustness of key endpoints further restrict the interpretability of results.

Importantly, the report explicitly states that findings should not be interpreted as causal, reinforcing the limitations of the available evidence base.

Strategic implications

This first JCA sends a clear signal for future EU submissions.

While indirect comparisons may be accepted in the absence of head-to-head evidence, they are subject to rigorous methodological scrutiny and full transparency on uncertainty.

More importantly, this assessment confirms that early evidence planning aligned with HTA requirements is becoming critical, particularly in areas where randomised evidence may be limited.

Conclusion

This first publication is more than a single assessment — it is a signal document for the future of EU HTA.

It confirms that EU HTA is now operational, and that expectations on clinical evidence are becoming increasingly structured and transparent.

RPN supports companies in navigating the evolving EU HTA landscape, from early evidence strategy to JCA readiness, ensuring alignment between regulatory and market access requirements and strengthening the robustness of submissions across Europe.

The Italian Medicines Agency (AIFA) has introduced a new framework to streamline price and reimbursement (P&R) negotiations, aiming to shorten timelines, accelerate patient access, and focus regulatory effort on high‑complexity dossiers.

The reform introduces two pathways: simplified procedures and fast‑track procedures.

Simplified procedures bypass the Scientific and Economic Commission (CSE) and are directly reviewed by AIFA’s Pricing and Reimbursement Office and the Board of Directors. They apply to well‑established scenarios such as equivalents and biosimilars, extension of indications, packaging changes, parallel imports, and automatic renegotiations via a Smart Dossier, provided pricing aligns with predefined benchmarks.

Fast‑track procedures still involve the CSE but rely on standardized assessments and predefined negotiation parameters. They cover cases such as strength or dosage changes, fixed‑dose combinations, renegotiations for drugs in short supply or under spending caps, and streamlined classification in Class C when comparable products (e.g. vaccines) are already classified within the same reimbursement framework.

Overall, AIFA is moving toward a more agile, risk‑proportionate P&R system—reducing administrative burden, improving predictability for companies, and enabling faster access to medicines for patients.

In this evolving regulatory landscape, targeted local expertise becomes essential. Regulatory Pharma Net (RPN) supports pharma and biotech companies in assessing eligibility for simplified or fast‑track pathways, preparing aligned dossiers, and managing interactions with AIFA. This approach helps companies navigate procedural changes efficiently and make effective use of the new opportunities offered by the updated framework.

The European Commission has officially completed the EU Health Technology Assessment (HTA) framework by publishing the final implementing act that defines how Joint Clinical Assessments (JCAs) will be conducted for medical devices and in vitro diagnostics (IVDs) under Regulation (EU) 2021/2282.

Published on 17 October 2025, this is the sixth and last implementing act required for the full application of the HTA Regulation, which became effective on 12 January 2025. The implementing act enters into force on 9 November 2025, marking a major milestone in building a unified, transparent European HTA system.

Key Points

• Establishes procedures for cooperation between Member States, the European Commission, notified bodies, and expert panels.
• Defines how developers, patients, and clinical experts are engaged throughout the assessment.
• Introduces standard formats and templates for dossier submissions and joint assessment reports.
• Clarifies processes for stakeholder consultation and evidence presentation, ensuring consistency across Member States.

Why It Matters

This regulation provides clarity and predictability for medical device and diagnostic manufacturers entering the EU market.
For regulatory, legal, and market access teams, it is time to:

• Align evidence-generation strategies with JCA requirements;
• Prepare dossiers following the new templates;
• Plan early stakeholder engagement with clinical and patient organisations.

The completion of the HTA framework represents a shift toward harmonised, patient-centred assessments that will streamline access to innovative technologies across Europe.

RPN remains committed to monitoring regulatory developments and providing timely insights to help stakeholders navigate the evolving landscape of health technology assessments in Europe.
Through continuous engagement and expertise in regulatory affairs and market access, RPN supports companies in aligning their strategies with the latest EU requirements to ensure successful and compliant market entry.