Italy was the first and among the hardest-hit countries in Europe by the COVID-19 pandemic. Extraordinary measures have been quickly adopted in order to contain the contagion and treat COVID-19 patients. In Italy earlier than in other European countries, the pandemic has posed an unprecedented challenge to clinicians, regulators and to the industry to make available in an incredibly short time frame medicinal products and medical devices that may be effective against COVID-19. The approach that the Italian competent authorities are following is to ensure that new treatments are made available in a regulated context. This is essential in order to collect reliable data and to safeguard patients.

New provisions have been enacted to speed up the approval process of clinical trials ("COVID-19 clinical trials") and compassionate uses concerning medicinal products and medical devices. In particular, the emergency regulation for clinical trials and compassionate uses is contained in Article 17 of the Law Decree No 17 of 18 March 2020.

Temporary application

The emergency regulation applies for so long as the state of emergency is in force. It was declared by the Decree of the Council of Ministries dated 31 January 2020 and it is provisionally set to expire on 31 July 2020.

Authorisation procedure for COVID-19 clinical trials

The authorisation for COVID-19 clinical trials for medicinal products is granted by AIFA. The Ministry of Health is the competent authority for medical devices. The COVID-19 clinical trials are to be conducted in compliance with the Good Clinical Practice (GCP). Insofar, the application of the ordinary rules is confirmed.

AIFA's immediate access to data

On an exceptional basis and for the duration of the emergency, AIFA shall have full and immediate access to the data collected in COVID-19 clinical trials. The provision applies also to compassionate uses and is intended to provide AIFA with constantly updated information on the clinical research process. The monitoring should allow AIFA to better evaluate the opportunity and conditions for the authorisation of other COVID-19 clinical trials, compassionate uses and off-label uses according to the evolution of the clinical landscape.

Information to the Civil Protection on AIFA's assessments of protocols

While the technical and scientific committee (CTS) of AIFA shall assess the protocols of COVID-19 clinical trials according to the ordinary rules, AIFA shall exceptionally inform the technical committee of the Civil Protection (the Italian counterpart of FEMA) on the outcome of such assessment. This is intended to keep the Civil Protection up to speed on treatment opportunities that may ease the demand of health care services by the affected population.

Central Ethics Committee at Istituto Spallanzani in Rome

For the period of the emergency, the ethics review of COVID-19 clinical trials concerning either medicinal products or medical devices is performed by the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani ("Istituto Spallanzani") of Rome, which shall grant opinions that are effective for the for the entire national territory. The Istituto Spallanzani shall receive from the sponsors the protocols relating to Phase II, III, and IV COVID-19 clinical trials and the amendments thereof.

The rationale of the provision is to speed up the approval process thanks to a single national body (instead of the multitude of Ethics Committee that are competent based on territorial criteria). In addition, the measure should increase the quality of the review as it is allocated to an institution (the Istituto Spallanzani) which is among the most reputed hospitals in Italy for the treatment of infectious diseases.

Publication of the Ethics Committee's opinions in AIFA website

The Ethics Committee shall communicate its opinions to AIFA, which shall provide for their publication in its institutional website. As a matter of fact, AIFA website is making available not only the opinions of the Ethics Committee but also other relevant documentation as the study protocols and synopsises. To date, AIFA's dedicated webpage lists six ongoing clinical trials. In two instances, the clinical trial is an investigator initiated study (IIS); in the other instances, the clinical trial is sponsored by pharmaceutical companies.

The purpose of this provision is to ensure the transparency on the ongoing clinical research and, at the same time, to facilitate the exchange of information among clinicians and in the scientific community.

COVID-19 compassionate uses

Compassionate uses may be an effective instrument to bring to the patients in a short timeframe unauthorised medicinal products for which evidence of safety and potential efficacy in the treatment of COVID-19 is available. As we have already mentioned, some provisions of Article 17 of the Law Decree No 17 of 18 March 2020 also apply to compassionate uses.

On 26 March, 2020, AIFA issued guidance on the implementation of Article 17 as far as compassionate uses are concerned. In the guidance AIFA draws a distinction between compassionate use programs (CUPs), which are intended to the treatment of a cohort of patients, and named patient compassionate uses (NPUs). Under a CUP, several patients are treated according to the criteria of inclusion, exclusion and the treatment scheme described in a protocol submitted by the pharmaceutical company supplying the medicinal product. The NPU concerns the case of a named patient use within a single hospital facility, based on scientific evidence and on a clinical protocol submitted by a physician. AIFA clarifies in the guidance that the exceptional regulation set out in Article 17 of the Law Decree No 17 of 18 March 2020 applies only to CUPs, while NPUs follow the ordinary route.

The request for the activation of a COVID-19 CUP must be submitted to the Ethics Committee of the Istituto Spallanzani in Rome and to AIFA, which shall provide their opinion and authorisation as a matter of urgency. The informed consent must be made immediately available for the Ethics Committee's review, while the modalities for the collection of the data could be submitted at a later stage, in a separate communication.

Due to the emergency situation, the submission of COVID-19 CUPs by pharmaceutical companies does not need to be filed in compliance with the deadline of at least 15 days before the scheduled activation of the CUP.

Also, in order to facilitate the rapid activation of COVID-19 CUPs and NPUs, pharmaceutical companies may immediately start importing the medicinal products needed for the compassionate use on the ground of either: (i) the preliminary favourable opinion of AIFA; or (ii) the favourable opinion of the Ethics Committee.

The CUP or NPU that have received a favourable opinion should be published in the institutional website of AIFA (at the moment, no programs are listed).

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