According to AIFA disposition n. 371 dated April 14^th 2014, in the case of variations with impact on Package Information Leaflet (PIL) and/or labelling texts, AIFA allows the Marketing Authorization Holder to sell out the not updated stocks, on condition that the PIL/labelling texts are made available to pharmacists within 30 days from the publication of the variation approval in the Official Journal.

The changes, affecting the texts, that fall into the AIFA disposition, are the following:

• restriction of therapeutic indication;
• restrictive changes of posology;
• addition of a new contraindication;
• special warnings and precautions;
• interactions with other medicines and other interactions;
• use during pregnancy and breast-feeding;
• addition of side effects and/or change of the frequency of the ones already described;
• overdose;
• restrictive change of storage conditions;
• restrictive change of shelf-life after first opening

The obligations stated in the AIFA disposition are generally fulfilled through an electronic system for the collection and management of PIL/labelling texts.

Using this system, the updated version of the PIL and labelling texts is made available to the pharmacists, allowing them to provide the patients with the current version of the texts.

Consequently, following the approval of one of the above changes, the batches not including updated PIL/labelling can be maintained into the Italian market until the expiry date stated in the label.

Unless AIFA issues a different product-specific decision, this disposition avoids the recall from the Italian market of medicinal products with not updated texts.

We are getting close to the deadline relevant to the payment of the annual fee due to AIFA.

Every year, within the end of July, each Marketing Authorisation Holder (MAH) is required to pay to AIFA an annual fee for each of its marketing authorization (MA 6 digits) valid at December 31^st of the previous year, as arranged by the deliberation No. 21 of May 30^th 2012 by virtue of which the AIFA board of directors has implemented the art. 4, par. 5 of the Ministry of Health Decree dated March 29^th 2012, No. 53 and the annual fee has been introduced.

The annual fee has to be paid through the online system available on the AIFA institutional portal (AIFA Front-End), via the specific Company access.

A fee reduction is applied for Small-medium enterprises (SMEs) upon submission of the appropriate documentation.

The fee is not due for MAs registered through centralized procedure.

AIFA publishes an alert close to the deadline on its institutional website and each MAH entering into the AIFA system can retrieve the amounts to be paid, and the payment modalities.

Companies are required to check the accuracy of the amounts assigned and to communicate with appropriate documentation the relevant amendments, if necessary.

Regulatory Pharma Net team is available to support companies to comply with this requirement.

According to the definition reported in the Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders (MAHs) in the Union (EEA) adopted by HMA and EMA, the shortage of a medicinal product occurs when “supply does not meet demand at a national level”.

A medicinal product is considered in shortage when it is not available in the national territory and the MAH cannot temporarily guarantee a continuous and appropriate supply respect to the therapeutic need of patients, for example due to manufacturing issues or unexpected product requests increase.

The Italian Agency makes available on its official website the updated list of medicinal products facing a shortage situation and, following a case-by-case basis, can authorize the MAH to import the medicinal product from abroad or in case the specialty is difficult to retrieve, can authorize the health facilities that request the concerned medicinal product to import similar products. Moreover, the Agency can temporarily stop the export to limit the shortage.

Regarding shortage situations, temporary or definitive end of commercialization of medicinal products, AIFA recently published an informative note to provide indications to the MAHs on the modalities for the application of the dispositions foreseen by the Legislative Decree n. 219/2006, as modified by the so called “Decreto Calabria”, converted into the Law n. 60 dated June 25th 2019.

In particular, AIFA indicated:

• Responsibilities of MAHs
• Timing to be considered to inform the Italian Authority
• Mandatory information to be provided to AIFA
• Sanctions applied in case of non fulfillment of the requirements
• Criteria followed by AIFA in order to apply the sanctions

RPN is available to support MAHs in the fulfillment of the Law requirements.

The Q&A developed by European Commission, EMA and the European medicines regulatory network provides guidance to companies on adaptations to the regulatory framework in order to address challenges arising from the COVID-19 pandemic.

Hot regulatory topics include renewals and “sunset clause”.

Renewals

In case the MAH is not able to respect the submission deadline due to pandemic, the relevant Competent Authority should be contacted before the deadline in order to discuss and agree on the steps to take.

“Sunset Clause”

In case the pandemic circumstances change the launch plans of a company, triggering the sunset clause mechanism, MAHs can request an exemption to the relevant Competent Authority making reference to the pandemic situation.

RPN is ready to promptly support the MAHs in liaising with the Authority during COVID-19 emergency to discuss flexibility on regulatory procedures.