Managing shortages between regulatory obligations and patients’ protection
The market shortage of medicinal products is now a global issue, that is continuously discussed by regulatory authorities and trade associations. It is a particularly sensitive topic, involving more stakeholders and presenting management difficulties for drug agencies, health systems, doctors, pharmacists, and above all, patients.
According to a recent report, more than 60 drugs would be almost impossible to be found in the sole European Union: a situation reported by 95% of the Member States, that seems not to have improved. The most alarming data are, however, those regarding the types of drugs under shortage.
These are not secondary therapies but essential products such as treatments for the gastrointestinal and nervous system, cardiovascular agents, anti-infectives, oncological therapies, insulins, antibiotics.
What is the cause of the shortages?
At the base of the out-of-stocks there are multiple causes, starting with the difficulty to find the active substance, whose supply can be disrupted due to external factors. Being pharmaceutical manufacturing concentrating in a few geographic areas, a natural disaster or a complex geopolitical situation can delay the supply chain.
In many cases, unavailability is due to manufacturing issues, often linked to quality or non conformities of the manufacturing site: the cycle is stopped for some time and the whole chain suffers from delays. And in cases like this, finding an alternative manufacturing site is difficult if the manufacturing process requires a specialised competence that is not easy to replace.
Sometimes, the manufacturing process is disrupted by regulatory measures (e.g. changes in the manufacturing process, authorisation variations, measures required following inspections) or regulatory processes, needed to ensure the drag safety and efficacy.
This kind of actions put the active substance production in stand-by for a certain period of time (to allow, for instance, manufacturers to comply with new compliance requirements), thus contributing to production delays.
Supply strategies by health services (that can create peaks in the demand) as well as market needs by companies (discontinuing less profitable products) are also at the root of stock-outs, together with health emergencies, as we have all seen during the Covid 19 pandemic.
When can a drug be considered as out-of-stock?
For a few years now, the problem has reached such extent to need dedicated laws and procedures, supporting authorities in taking measures suitable to monitor and limiting out-of-stocks, especially when concerning essential drugs that cannot be substituted.
According to the definition of the Italian Medicine Agency, a drug is out of stock when it is “temporarily unavailable in the national territory since the MA holder […] cannot ensure its continuous supply in relation to the patients’ needs”. It should be clarified that not all shortages are a problem for the patients’ health, because in many cases drugs can be replaced with equivalent or alternative products.
On this regard, AIFA has made available two lists of out-of-stock drugs, that are updated every month: those for which equivalent products are available on the Italian market; and those for which, although there are no equivalent products available, there are therapeutic alternatives on the market, also containing the same active substance. Specialists and general practitioners can take these medicinal products into consideration to ensure therapeutic continuity for the patient.
Measures taken by the AIFA
Along with the lists of out-of-stock drugs that can be substituted by equivalent or alternative products, the Agency permits to import a similar product from abroad, from the European Union as well as from extra-EU countries. The importation authorisation due to out-of-stock can be applied directly by a health facility or by the MA holder. The drug to be imported must have the same therapeutic effects and the same safety of the product authorised in Italy. Product information should also match. Moreover, the importer shall specify the quantities to be imported and the period covered by the imported quantities along with other administrative and quality information required to guarantee the safety of the imported medicinal product.
The AIFA can also stop exportation of monitored products to prevent or limit any shortage on the national territory. Also in these cases, there are updated lists available including out-of-stock drugs for which the authorisation of importation from abroad can be released and those that cannot be removed from distribution and sale.
MAH’s obligations
MA holders have the obligation of informing the Agency about any presumed shortage regarding their products, via the Shortage Front End (Front End Carenze, FEC) activated as of 2020. Here, MA holders can manage all communications regarding any shortage of cessation of the marketing of the medicines sold in Italy. Alternatively, it is possible to send a certified e-mail (PEC). Last December, the so called “Simplification Law” (Legge Semplificazioni) reduced the notice deadline for the communication of out-of-stocks by MA holders from 4 to 2 months in advance, clearly specifying the administrative fines (6,000 to 36,000 euros) in case of violation, “regarding pack sizes included in a specific list published and periodically updated by AIFA, laying down medicines for which dedicated measures have been taken to prevent or limit any shortage or unavailability, also temporary, on the market or with no valid therapeutic alternatives.”
The support of Di Renzo Regulatory Affairs
Di Renzo Regulatory Affairs can support companies in the communication of drug shortage, promptly organising any information required to comply with the strict timetable imposed by the regulations.
We offer our assistance for the communication on out-of-stock drugs in the AIFA Shortage Front End (FEC) or for the submission of information via PEC. We can also cooperate with MA holders for the submission of importation authorisation applications due to shortage from other countries, interfacing with the authorities and starting all procedures required to support MA holders.
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