Short and long-term shortages of medicinal products have been a global problem which increasingly affects the European Union since the past years.
In the European Union, most medicinal product shortages are dealt with at national level by the national competent authorities. However, the EMA can be involved in certain situations, for example when a medicine shortage is linked to a safety concern or affects several Member States.
Shortages of medicinal products can occur for many reasons along the manufacturing and distribution chain, such as manufacturing difficulties or problems affecting the quality of medicinal products.
To prevent medicinal product shortages, France implemented into the French Public Health Code (CSP) Article 81 of Directive 2001/83 as modified according to which “the holder of a marketing authorization for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medicinal product to pharmacies and persons authorized to supply medicinal products so that the needs of patients in the Member State in question are covered”.
Article L.5124-6 CSP sets down an obligation of information of the pharmaceutical company exploiting in France a medicinal product (the so-called “exploitant” under French law). The said company must inform the French Agency ANSM of its intention to suspend or stop the marketing of a medicinal product at least one year before the suspension or stop when the product is used for a rare disease for which no therapeutic alternative exists. The same obligation applies if the company has knowledge of facts that could result in the suspension or termination of such marketing. The time-period is of two months for other medicinal products. The end of the marketing cannot start before alternative solutions have been found.
Furthermore, the company must inform the ANSM of any risk of shortage of a medicinal product. If the medicinal product is used for a serious pathology for which no alternatives are available on the French market, the company must collaborate with the ANSM to implement alternative solutions and accompanying measures.
Decree No. 2012-1096 dated 28 September 2012 furthermore aims at preventing shortages of medicinal products.
The “supply disruption” of a medicinal product is defined by Article R.5124-49-1of the French Public Health Code as an inability for a pharmacy or hospital pharmacy to deliver a medicinal product to a patient within 72 hours.
Decree No. 2012-1096 strengthens the obligations of pharmaceutical companies and of wholesalers regarding the prevention and the actions to be taken in case of shortage of medicinal products.
When a pharmaceutical company anticipates a situation of potential supply disruption, it must inform the French Agency ANSM and specify the time of occurrence, the available stock, availability conditions and the forecast of when the product be again available and the identification of medicinal products that can be substituted to the missing product if necessary.
The pharmaceutical company must permanently have in place call centers for pharmacists, hospital pharmacists and wholesalers’ qualified persons. The telephone number of these call centers must be made available by the companies which ensure the traceability of the calls received.
These call centers must be organized to support anytime supply disruptions affecting medicinal products and enable the effective dispensation of the missing product.
The company must inform quarterly the competent ARS (“Agence Régionale de Santé”: Regional Health Agency) of urgent supplies and of declarations made.
It is of the responsibility of the ANSM to inform the healthcare professionals of the effective or anticipated supply disruptions and to give recommendation to manage the shortage.
Within the “exploitant”, the “pharmacien responsable” is responsible for the compliance with these provisions (the qualified person has to be a pharmacist in France). The “pharmacien responsable” is personally liable for non-compliance with these obligations in case of shortage.
Besides the pharmaceutical companies, the wholesalers also have to ensure appropriate and continued supplies of medicinal products so that the needs of patients in France are covered.
The wholesalers have a public health mission on their territory. The wholesaler must, for example, hold in stock at least 90% of all medicinal products used in France and have a 2 week supply capacity for their usual customers.
According to Article R.5124-59-1CSP, they must also inform pharmaceutical company of any disruption that they have knowledge of.
Both the pharmaceutical company and the wholesaler can be financially sanctioned (up to 10% of the turn-over in the limit of 1 million euros) by the ANSM in case of non-compliance with these provisions relating to medicinal product shortage.
The new bill of Law (Projet de Loi de Santé) which has been adopted in first lecture by the French National Assembly on 14 April 2015 contains some additional provisions on shortage of medicinal products (Article 36). The bill of Law reminds of the obligation of appropriate and continued supply, which will apply to “exploitant” but also to marketing authorization (MA) holders. This is an important addition to the current text since a MA holder which exploits the product in France through its local subsidiary may be held liable according to this new provision.
One of the main novelty is the creation of a shortage management plan for major therapeutic interest medicinal products (“médicaments d’intérêt thérapeutique majeur”) for the prevention and the management of shortage as well as the information of pharmacists and wholesalers.
The definition of major therapeutic interest medicinal products will be given by a new Article L.5111-4 CSP: “medicinal product for which an interruption of treatment may in the short to medium term life-threaten patients, or represents a significant loss of chance for patients compared to the severity or the potential evolution of the disease”.
Pharmaceutical companies will have to declare the list of these products to the ANSM.
In case of shortage of one of these major therapeutic interest medicinal products, the company will have to inform the ANSM of the situation and to set up, after approval of the ANSM, alternative solutions and implements the shortage management plan in particular with the help of patient associations.
Finally, the bill of Law limits the exportations by wholesaler of major therapeutic interest medicinal products.
The bill of Law will now be examined by the French Senate before its adoption in accordance to the accelerated procedure chosen by the French Government for the faster adoption of this bill of Law. These shortage provisions were not the subject matter of long discussions within the National Assembly.
Pharmaceutical companies and wholesalers in France will have adapt the management and monitoring of potential shortage to this new rules and inform their contractual partners of any shortage management plan.