Post-Authorization Safety Studies (PASS) are vital tools for monitoring the safety of medicines after they have been approved for use in the general population. In the European Union (EU), these studies are conducted within the framework established by the European Medicines Agency (EMA). However, when conducting a PASS under the EMA framework, there might be additional specific local requirements that must be followed in addition to EMA’s general guidelines. Italy’s national regulatory authority, the Italian Medicines Agency (AIFA), oversees the implementation of PASS within the country, ensuring compliance with national legislation and ethical standards.
Below are key local requirements and considerations when conducting a PASS in Italy:
1. National Regulatory Framework
AIFA Oversight: AIFA (Agenzia Italiana del Farmaco) is responsible for regulating medicines, including PASS, within Italy. All PASS conducted in Italy must be registered with AIFA, and AIFA may provide specific guidance on study design, conduct, and reporting.
Harmonization with EMA Requirements: The legal framework for pharmacovigilance in Italy is harmonized with EU directives, particularly Directive 2001/83/EC and Regulation (EC) No 726/2004 which govern PASS across Europe. However, AIFA has its own guidelines that must be followed when submitting and conducting a PASS locally.
National Law No. 79/2014: This law outlines Italy’s implementation of EU pharmacovigilance requirements and includes provisions on reporting adverse drug reactions, conducting post-marketing studies, and ensuring public health safety.
2. Ethical Approval and Local Ethics Committees
In Italy, approval from a local Ethics Committee (Comitato Etico) is mandatory before initiating a PASS. These committees are responsible for reviewing the ethical aspects of the study, ensuring that patient safety is prioritized, and confirming that the study design aligns with both national and international guidelines. In multi-center studies, multiple ethics committees may be involved, with a lead committee often coordinating the approval process. In accordance with Italian law, participants must provide informed consent, and the process for obtaining consent must be clearly documented and approved by the Ethics Committee.
3. Notification to AIFA
Study Registration: The PASS must be registered with AIFA through the Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC), the National Monitoring Centre for Clinical Trials. This registry ensures transparency and compliance with national and EU regulations.
Submission to AIFA: Before starting the study, the protocol and all relevant documentation must be submitted to AIFA for review. While AIFA does not need to approve the study for it to begin (unlike the Ethics Committees), the agency must be notified.
Ongoing Reporting: AIFA requires regular updates on study progress and any emerging safety signals. These updates must align with both AIFA and EMA reporting timelines.
4. Data Privacy and Protection
General Data Protection Regulation (GDPR): As with other EU countries, PASS conducted in Italy must comply with the GDPR for data protection. This includes safeguarding patient data, ensuring data are anonymized or pseudonymized to guarantee privacy, and explicit consent must be obtained for data use.
National Data Protection Authority: The Italian Data Protection Authority (Garante per la protezione dei dati personali) enforces additional privacy regulations within Italy, especially concerning health data. Researchers conducting PASS must ensure that their data collection and processing meet the stringent requirements set by both GDPR and national laws.
5. Patient Registries and Data Sources
National Healthcare Data: Italy’s National Health Service (Servizio Sanitario Nazionale - SSN) and various regional healthcare databases can provide valuable data sources for PASS. Access to these data sources may require formal agreements with the relevant regional health authorities and compliance with local data sharing regulations.
Rare Disease Registries: For PASS related to rare diseases, Italy’s extensive network of disease-specific registries is an important resource. These registries provide critical data on patient outcomes and drug safety in small populations. Collaboration with regional authorities and institutions managing these registries is essential for accessing the data.
6. Adverse Event Reporting
National Reporting Requirements: Italy has its own national pharmacovigilance system for reporting adverse events, managed by AIFA. Sponsors conducting a PASS must report any adverse drug reactions (ADRs) detected during the study to both AIFA and EMA’s EudraVigilance system.
Reporting Timelines: Adverse events must be reported within the required timelines, which may be faster than in other countries for certain types of events (e.g., serious adverse events). Compliance with both AIFA’s and EMA’s timelines is mandatory.
7. Interim and Final Reporting to AIFA
Interim Reports: Depending on the study design and timeline, AIFA may request interim reports on the progress of the PASS, including patient recruitment, safety findings, and any emerging safety signals.
Final Report Submission: Upon completion of the study, a final report must be submitted to AIFA and EMA, summarizing the study’s findings, including the safety profile of the product in question and any recommended changes to the risk management plan.
Publication of Results: Transparency is emphasized in Italy, and AIFA encourages the publication of study findings, particularly if they have significant public health implications.
8. Local Collaboration and Stakeholder Engagement
Collaboration with Italian Healthcare Institutions: Engaging with Italian clinical research centers, hospitals, and patient advocacy groups is critical to the success of a study. Many centers have expertise in pharmacovigilance and long-term safety studies, making them valuable partners in both study design and patient recruitment.
Role of Patient Organizations: Italy has a strong tradition of patient advocacy, particularly in the area of rare diseases. Engaging with patient organizations can help researchers ensure that the study addresses patient-relevant outcomes and improves patient participation rates, particularly in long-term follow-up studies.
In conclusion, conducting a PASS in Italy requires adherence to both EU and local regulatory requirements, including approval from Ethics Committees, AIFA oversight, and GDPR compliance. AIFA plays a crucial role in ensuring that PASS complies with Italian pharmacovigilance standards, while local Ethics Committees provide ethical oversight. Researchers must also navigate the complexities of patient recruitment, data protection, and adverse event reporting in Italy. By adhering to these regulatory and the collaboration with Italian healthcare institutions, patient registries, and rare disease networks can greatly enhance the feasibility and success of the study.
