Insights

PHARMACOVIGILANCE – MANAGEMENT OF REPORTS OF LACK OF EFFICACY IN THE NATIONAL PHARMACOVIGILANCE NETWORK

The Italian Medicines Agency (AIFA), in line with what is reported in the Guideline on good pharmacovigilance practices (GVP) Module VI and in the Ministerial Decree April 30th, 2015, has published an update concerning the management within the National Pharmacovigilance Network (RNF) of the reports of suspected adverse drug reactions related to lack of efficacy.

In general, the reports of suspected adverse drug reactions included in the RNF are those considered valid., i.e. the ones that have the four minimum requirements:

  • an identifiable reporter
  • an identifiable patient
  • one or more adverse reactions
  • one or more suspected medicines

The reports of lack of therapeutic efficacy must be collected and if they do not meet the minimum requirements follow-up attempt(s) must be performed.

It is important to determine whether it is a lack of therapeutic efficacy of the medicine or a disease progression. All cases in which it is believed that the aggravation or the progression of the disease are not to be attributed to the drug itself but to a natural evolution of the pathology should not be recorded in the RNF.

Normally, if those reports are not associated with suspected adverse drug reactions, they do not have to be recorded in the RNF, but they will be discussed in periodic safety update reports (PSUR) prepared by the marketing authorization holders, when applicable. However, in certain circumstances, those reports of therapeutic failure without suspected adverse reactions may require to be registered. Medicines used in critical conditions or to treat diseases that can be life-threatening to the patient, vaccines and contraceptives are examples of such circumstances.

In the event that the report of lack of therapeutic efficacy is to be recorded in the RNF the most appropriate MedDRA terms should be used to describe the clinical condition of the patient, according to what is reported in the most updated version of the guide MedDRA Term Selection: Points to Consider.

Biological drugs deserve special mention, for which a partial or complete loss of the efficacy of the product can occur.

For the reports of suspected adverse reaction resulting from biological medicines it is important to report the number of the organic batch indicated as suspect.

For more details you can find the full notice at the following link https://www.aifa.gov.it/en/-/comunicazione-aifa-sulla-gestione-delle-segnalazioni-di-mancanza-di-efficacia-nella-rete-nazionale-di-farmacovigilanza

RPN constantly monitors the AIFA website in order to stay up to date on pharmacovigilance and it is available to provide full support for any query and for the management of ICSRs.

Francesca Spera 11-06-2021

Insights

CLINICAL TRIALS – UPDATE OF SUBMISSION PROCEDURE AND AUTHORIZATION FORMS

The Italian Medicines Agency (AIFA) has published an update concerning the documentation for the submission of Phase I, II, III and IV clinical trial applications and related substantial amendments.

For authorization requests submitted through the OsSC platform, it will no longer be necessary to send to AIFA the package containing the paper documentation and the CD-ROM(s) provided that certain requirements are met.

However, the submission in transitory paper mode is permitted in the cases illustrated in the AIFA press release dated December 20th, 2018 ("Procedures to be followed in the event of OsSC malfunction").

In addition, new models of transmission letters have been published: further declarations have been inserted regarding the possible use of medical devices, artificial intelligence systems or Machine Learning.

For more details you can find the full notice at the following link: https://www.aifa.gov.it/en/-/aggiornamento-modulistica-autorizzazione-sperimentazioni-cliniche-ed-emendamenti-sostanziali

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.

 

Francesca Spera 21-06-2021

Insights

CLINICAL TRIALS – ENTRY INTO FORCE OF REGULATION (EU) 536/2014 AND CLINICAL TRIALS INFORMATION SYSTEM

The European Commission has confirmed that the entry into force of the Clinical Trials Regulation (EU) No 536/2014 and the go-live date for the Clinical Trials Information System (CTIS) will be on January 31st, 2022.

The Clinical Trials Regulation aims to harmonize the processes for clinical trials throughout the European Union.

Clinical Trials Information System will become the single-entry point for clinical trial application submission, authorization and supervision in the EU.

CTIS will support the coordinated assessment of safety reporting in the context of clinical trials highlighting the benefits and the risks of medicinal products and it will facilitate recruitment of trial participants. Moreover, CTIS will contain a public website with details and outcomes of all clinical trials conducted in the EU, thus improving transparency and access to information for patients, healthcare workers and other interested parties.

There will be a three-year transition period: for one year, until January 31st, 2023, applicants will be able to choose whether to submit the application according to the current system or according to the new regulation. Starting from January 31st, 2023, submission via CTIS will become mandatory and by January 31st, 2025 all ongoing trials approved under the current directive will have to pass to the new Regulation and to the CTIS.

RPN will provide any further update on this hot topic and 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.

Francesca Spera 25-10-2021

Insights

CLINICAL TRIALS – REGULATION (EU) 536/2014

The clinical trials evaluation system in Europe will face a radical change starting from January 31st, 2022, with the full application of Regulation (EU) no. 536/2014.

With this Regulation, the European Union aims to promote the clinical trials efficiency, especially in the case of trials carried out in several Member States, while stimulating innovation and limiting duplication of evaluation and repetition of clinical trials without added value.

The dedicated portal for the management of all trials in Europe (Clinical Trials Information System, CTIS) will be fundamental for transparency and to strengthen collaboration, information exchange and decision-making processes between Member States and within them.

The authorization and supervision of clinical trials will remain under the responsibility of the Member States, while the EMA will manage the CTIS and the release of its contents in the public section of the portal.

To be ready for the entry into force of the Clinical Trials Regulation (EU) No 536/2014 and the go-live date for CTIS, RPN will provide any further update on this topic and is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments.

 

Francesca Spera 04-01-2022

Insights

CLINICAL TRIALS – TRANSITIONAL OPERATING PROCEDURE FOR CLINICAL TRIALS IN ITALY ACCORDING TO REGULATION (EU) NO. 536/2014

With the activation of the CTIS on January 31st 2022, Clinical Trials Regulation (EU) no. 536/2014 has officially entered into force, leading to a radical transformation in the management of clinical trials in the European Union (EU) and in the European Economic Area (EEA).

In Italy, while waiting for the finalization of the Ministerial Decrees for the Ethics Committees reorganization and the introduction of a single fee for national adaptation to EU legislation, it is possible to submit through CTIS a partial application, relating only to "Part I" of the dossier.

"Part II" can be submitted through the transitional operating procedure which allows the presentation of Part II of the dossier and have full national approval in compliance with the requirements of the Regulation.

For more details you can find the full notice at the following link: https://www.aifa.gov.it/en/-/operativi-regolamento-gestione-armonizzata-sc-ctis

RPN will provide any further update on this hot topic and is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments.

 

Francesca Spera 10-02-2022

Insights

PUBLICATION OF THE UPDATED AGREEMENT TEMPLATE BY THE NATIONAL COORDINATION CENTER OF ETHICS COMMITTEES FOR CLINICAL TRIALS ON MEDICINES FOR HUMAN USE AND ON MEDICAL DEVICES

The National Coordination Center of Ethics Committees for clinical trials on medicines for human use and on medical devices has recently published the updated version the agreement for the conduction of:

  • Clinical trials on medicinal products
  • Independent clinical trials on medicinal products
  • Clinical investigation on a non-CE marked medical device or CE marked but used outside the scope of its intended use

These models have been adopted according to the Art. 2 of Law 11 January 2018, no. 3, which attributes to the Coordination Center the same functions of coordination, guidance and monitoring of the evaluation activities of the related ethical aspects to clinical trials on medicines for human use delegated to the Ethics Committees.

Moreover, to ensure procedural uniformity in the application of Regulation (EU) no. 536/2014, the National Coordination Center has also released the template for the following documents:

  • Site-specific feasibility
  • Compensation for clinical trial participants
  • Declaration of interests
  • Curriculum vitae principal investigator

Considering this hot topic, that is currently being explored at European level, the proposed models could be further modified.

RPN will provide any further update and is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments.

Contact us at info@regulatorypharmanet.com

 

Francesca Spera 22-06-2022

Insights

PHARMACOVIGILANCE IN ITALY – THE NEW NATIONAL PHARMACOVIGILANCE NETWORK

The National Pharmacovigilance Network (RNF), that is the system by which reports of suspected adverse drug reactions (ADRs) are collected, managed and analysed in Italy, has been renewed. The new RNF features advanced functions for the management and analysis of ADRs reports in order to ensure an increasingly accurate assessment of the safety profile of medicinal products.

Among the news:

  • a new international standardised format ISO Individual Case Safety Report (ICSR) ICH E2B(R3) for ADRs reporting has to be used in all EU countries to send and receive ADRs reports to and from the EudraVigilance System, with which the RNF is closely linked.
  • for each pharmaceutical company, in addition to the appointment of the local contact person for pharmacovigilance on behalf of the pharmaceutical company, the deputy may also be appointed to support the local contact person in the management of reports of adverse reactions and/or take his/her place in the event of temporary absence.
  • the appointment of a local contact person is required even if this role is assigned to the EU QPPV. Both the local contact person and the deputy will have to register themselves in the AIFA portal and to send a separate request to AIFA for their appointment, that should be then approved by the Company Users' Administrator (CUA).
  • any updates to the EU QPPV are directly accessible by AIFA through the art. 57 database, however any updates to the CUA or to the local contact person for pharmacovigilance or his/her deputy shall be updated in the AIFA portal, even if the role is assigned to the EU QPPV.

Moreover, there is a new online reporting method that complies with the new international standard format and has replaced the "Vigifarmaco" portal. So, healthcare professionals and patients/citizens can report a suspected adverse reaction through one of the following procedures:

  • By filling in the reporting form and sending it via e-mail or fax to the Pharmacovigilance contact point of your facility, or to the Marketing Authorization Holder (MAH) of the drug suspected to have caused the adverse reaction
  • Online on the AIFA website 

RPN constantly monitors the AIFA website in order to stay up to date on this topic and is available to provide full support for the appointment of the local contact person for pharmacovigilance and his/her deputy and for the management of any local pharmacovigilance activity.

 

Francesca Spera 19-09-2022

Insights

EVALUATION OF A CLINICAL TRIAL APPLICATION IN ITALY ACCORDING TO REGULATION (EU) NO. 536/2014

According to the Regulation (EU) no. 536/2014, the evaluation of a clinical trial application in CTIS includes three main steps:

  • validation
  • evaluation
  • final decision

The evaluation phase can take up to 45 days, which can be extended by a maximum period of 31 days if requests for additional information are made.

The process includes Part I and Part II evaluations (which may or may not occur at the same time) that end with two respective assessments.

Part I assessment consists of a joint assessment of the concerned Member States led by the Rapporteur Member State, which presents the final decision, while Part II consists of a separate assessment carried out by each Member State.

In Italy, the Ethics Committees assess the aspects included in Part II independently and are responsible for presenting the relevant conclusion.

RPN will provide any further update and is available to provide full support for any query and for the submission of Clinical Trial Applications and relevant amendments.

 

Francesca Spera 04-11-2022

Insights

REGISTRY OF OBSERVATIONAL STUDIES (RSO) IN ITALY

Starting from January 31st, 2023 the Registry of Observational Studies (RSO) will be activated on the AIFA Portal.

The RSO is the management tool required by current legislation and it is complementary to the National Observatory on Clinical Trials (OsSC) for interventional clinical trials.

This system will enable the submission of the authorization request for an observational study to the involved Ethics Committee, subject to the registration to the system.

The submission through this new tool is limited to the initial request and it is mandatory only for new applications submitted from January 1st 2023 with exception for the observational studies on COVID-19 for which it is recommended to proceed with the registration of all studies submitted to the Ethics Committee since the start of the pandemic.

Any changes to the study data (amendments), including the subsequent addition of clinical sites, do not require an update of the study dossier.

Moreover, the new RSO system will allow external registered users to search and consult observational studies.

For more details you can find the full notice at the following link: https://www.aifa.gov.it/en/-/registro-degli-studi-osservazionali-rso-attivazione-a-partire-dal-31-gennaio-2023

RPN is ready to provide support with the registration to this new AIFA Registry and for any submission of authorization requests for observational studies.

Francesca Spera 12-01-2023

Insights

REORGANIZATION OF THE ETHICS COMMITTEES IN ITALY

The four decrees on the reorganization of the Ethics Committees, which are a further step towards the full implementation in Italy of the Regulation (EU) no. 536/2014 on clinical trials, have been published in the Official Journal n.31 of 02-02-2023.

The Ministerial Decree of 26 January 2023 identifies the 40 territorial Ethics Committees which have the task of evaluating clinical trials on medical devices and medicines for human use.

Furthermore, the Ministerial Decree of 27 January 2023 regulates the transitional phase in relation to evaluation activities and interactions between the Coordination Centre, the territorial Ethics Committees, the National Ethics Committees and AIFA.

Another important provision has been accomplished with the Ministerial Decree of 30 January 2023, that has led to the determination of the single fee for clinical trials.

Finally, the other Ministerial Decree of 30 January 2023 defines the criteria for the composition and functioning of the territorial Ethics Committees.

 

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.

Francesca Spera 17-02-2023