In view of the new European legislation (EU Regulation 536/2014) about the clinical trial, the Law No. 3 of 11 January 2018 (so-called “Legge Lorenzin”) was definitively approved in Italy.

The main purpose of this law is to acquire greater international competitiveness in the field of clinical trials through the following provisions:

• Reorganization and reduction of existing ethics committees.
• Establishment of a National Coordination Center for Ethical Territorial Committees for clinical trials on medicinal products for human use and on medical devices, with the task of coordinating, guiding and monitoring the evaluation activities of ethical aspects related to experimentations.
• Identification, through a subsequent Ministerial Decree, of a maximum number of forty territorial ethics committees (compared to over 100 currently existing), and the recognition of three national ethical committees, one of which reserved for experimentation in the pediatric field.
• Single fee at Italian level.
• More transparency.
• Public and no-profit research valorization.

The first step for implementation of the “Legge Lorenzin” was the institution of the National Coordination Center for Ethical Territorial Committees by Italian Medicines Agency (“AIFA”). Consequently, since the Law allow the Government to issue one or more legislative decrees laying down the minimum content of Clinical Trial Agreements (“CTAs”) covering certain aspects of the conduction of a clinical trial, a public consultation on the two draft CTAs templates (one template for medicinal products and a second one for clinical investigations on medical devices) prepared by the National Coordination Center, has been launched by AIFA in order to collect comments and suggestions for improvements. The consultation of the CTA ended on May 10^th, 2019 and now AIFA is evaluating all the suggestions received.

Stay connected with us in order to know the next step!

Regulatory Pharma Net is available to provide full support for any query and for the submission of Clinical Trial Applications and the relevant amendments.

The Italian Medicines Agency (AIFA) has provided the following specific indications for the management of clinical trials in Italy during the COVID-19 emergency, valid until further notice.

• Submission of clinical trials and substantial amendments

1. If the CTA/amendment request is submitted through the OsSC portal, the submission of paper documents/CD-rom can be postponed. It is recommended, whenever possible, to apply the duty stamp on the transmission letter by virtual payment and to digitally sign the letter uploaded in the OsSC.
2. In case the submission via OsSC is not possible and paper transmission is needed, the transmission by e-mail will not be accepted. Exception is made only for the submission of clinical trials regarding treatment of COVID-19 (coronavirus disease 19).

• Ethics Committees evaluations of clinical trials/substantial amendments

Ethics Committees meetings are not suspended but they will be managed through web-conferences or other telematic procedures.

• Management of clinical trial activities outside investigational sites

If necessary and where feasible, in order to supply patients with the investigational drug(s) to avoid them going to the hospital or carry out other activities related to the clinical trial (e.g. visits and exams or adverse reactions management) at patient’s home or in a site different from the investigational clinical site, Sponsors will have to notify a substantial amendment for immediate implementation only to the Ethics Committees involved, indicating its urgency due to the current emergency.

Sponsors/CROs are invited to draw up a risk evaluation plan and implement an action plan for the maximum protection of the subjects, also in view of the urgent need to minimize contacts between patients and investigational staff, and not to overload healthcare facilities.

Some exemptions, limited to this emergency period, are provided for:

• Investigational Medicinal Product (IMP) management
• Clinical examinations
• Sites closing
• Clinical Trial monitoring
• Activities related to clinical management of patients falling under Principal Investigator’s (PI) responsibility
• Expenses reimbursement

For more details you can find the full notice at the following link:

https://www.aifa.gov.it/en/web/guest/-/gestione-degli-studi-clinici-in-italia-in-corso-di-emergenza-covid-19-coronavirus-disease-19-

Regulatory Pharma Net is available to provide full support for any query and for the submission of Clinical Trial Applications and the relevant amendments.

Following the Legislative Decree n.18 of 17/03/2020, AIFA has published a Circular indicating the simplified procedures for the data acquisition as well as the methods for joining the studies for the COVID-19 treatment.

CLINICAL TRIALS

The authorization requests shall be submitted to AIFA and National Ethics Committee of INMI Spallanzani (EC) through the OsSC platform. However, if there are some technical OsSC issues the following approaches are accepted:

• paper submission
• submission via certified email (PEC)

OBSERVATIONAL STUDIES

The observational studies shall be submitted by e-mail in parallel to AIFA and EC.

In order to speed up the assessment process, it is advisable to submit the proposals both for clinical trials and observational studies by using the specific form made available by AIFA.

The wording “COVID-19” should be reported in the subject of any communications.

For more details you can find the full notice at the following link: https://www.aifa.gov.it/en/web/guest/-/circolare-sulle-procedure-semplificate-per-gli-studi-e-gli-usi-compassionevoli-per-l-emergenza-da-covid-19

RPN constantly monitors the AIFA website in order to stay up to date on clinical trials and observational studies and it is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments as well as for the notifications of observational studies.

As of 31^st January, 2022, the Clinical Trials Information System (CTIS) has gone live and thus the Clinical Trials Regulation EU/536/2014 (CTR) has become officially applicable.

The CTIS is the centralised EU online portal and database for regulatory submissions, authorisations and supervision of clinical trials across the EU/EEA.

With CTIS, clinical trial sponsors can:

• Apply for a clinical trial in up to 30 EU/EEA countries with a single application

• Facilitate involvement of trial participants by allowing easy expansion of trials to other EU/EEA countries
• Collaborate across borders for better results and knowledge sharing
• Ensure the EU/EEA remains an attractive location for clinical research investment
• Fulfil all clinical trial publication requirements with no additional effort

Users with EMA accounts have a default role that will allow them to access CTIS and perform a limited number of activities. To perform additional actions relating to the CTs and, in accordance with their responsibilities, they need to be assigned specific roles by user administrators. This supports the proper management and oversight of the users using the system

CTIS has a total of 48 roles across the sponsor and authority workspaces including administrator and business roles.

There are two main approaches to manage a CTA in the CTIS:

Organisation centric approach:

• it is intended for big organisations managing a high number of users and CTs.
• It requires a formal registration process as the high-level administrator needs to be validated by EMA and appointed in the EMA Account Management portal.
• It creates the opportunity to manage access and roles across trials

Trial-centric approach: 

• it is expected to be used by non-commercial sponsors managing a small number of users and CTs.
• It is the default approach if the organisation for which a CTA is created does not have a high-level administrator registered.

This increases the agility when submitting a CTA or when managing a small number of users.

Sponsors have a one-year grace period before they must submit all new clinical trial applications through this system. Starting from January 2025, all new and ongoing trials must go through CTIS.

Regulatory Pharma Net is ready to provide full support for the submission of Clinical Trial Applications and relevant amendments through the EU portal CTIS.

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Just contact us at info@regulatorypharmanet.com

As of March 6^th, 2022, with the entry into force of the Ministerial Decree of November 30^th, 2021, concerning the measures intended to facilitate and support the conduct of no-profit clinical trials of medicines and observational studies and the transfer of the relevant data and results for registration purposes, important changes have been introduced in Italy for the management of these kind studies.

One of the most important innovation concerns the transfer of data and results of non-profit trials for registration purposes; in particular:

• The transfer of data and results of no-profit trials for registration purposes can be performed both during the trial and after its completion
• When data and/or results are transferred for registration purpose in Italy or abroad:
  • Sponsor has to bear and reimburse all direct and indirect expenses concerning the trial and pay the relevant fees due to Italian Authority and Ethic Committee;
  • an estimate of the value of the asset in question in view of its expected commercial exploitation has to be performed by a patent advisor registered in the Register of Industrial Property Consultants
  • The transfer of data from no-profit trials must be regulated by means of a specific agreement between the sponsor and transferee.
• for companies who intend to start this kind of trials, financial benefit is expected.

Another important news concerns the observational studies, which will have to be entered by the Sponsor into a national register. Specific guidelines will be published by the Italian Competent Authority in the next weeks.

Regulatory Pharma Net is available to provide your company with any further updates on this topic and is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments.

If you wish to know more reach out to us at info@regulatorypharmanet.com

Starting from January 31^st, 2023 the new clinical trial applications have to be submitted only through the Clinical Trial Information System (CTIS) in accordance with EU Regulation 536/2014.

The CTIS is the current portal for Sponsors and Competent Authorities/Ethics Committee for the submission and assessment of clinical trials in Europe.

Thus, from January 31^st, 2023, the submission of new clinical trials via the “Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC portal)” is no longer possible.

The OsSC portal will remain active only to:

• upload the previous clinical trials submitted by January 30^th 2023;
• manage the studies (e.g. amendments submission, EoT communication, site addition) submitted via OsSC portal by January 30^th 2023 (this will be possible until January 30^th 2025).

From January 31^st, 2025 all clinical trials will be submitted and managed only through the CTIS portal.

RPN will provide any further update and is available to provide full support for any query and for the submission of new Clinical Trial Applications and relevant amendments through the CTIS portal and for the management of ongoing clinical trials in this last transition period.