EU Survey Shows Wide Variations In How Countries Deal With Drug Shortages
Executive Summary
A survey of EU member states has shown wide variations in the way that they deal with shortages and discontinuation of medicines.
An EU-wide survey has revealed significant disparities in how member state authorities deal with shortages of medicines, and what they expect manufacturers, distributors and pharmacies to do in the event of actual or expected supply disruptions. There are also wide differences among the member states as to how they define supply disruptions, shortages and “critical” or “essential" medicines.
The results of the survey, conducted in autumn 2017, have been published by the European Commission following an ad hoc technical meeting of the Pharmaceutical Committee, an advisory body composed of senior public health experts from the member states. A total of 27 member states (excluding Luxembourg) and Norway answered the survey.
The meeting was held in response to calls from the European Parliament and Council for the commission to monitor the obligation on marketing authorization holders (MAHs) to ensure a continuous supply of medicines and notify any supply disruptions, as required under EU legislation (Directive 2001/83).
The committee agreed on a summary of the measures implemented in the various countries as well as a question and answer document on the obligations of the respective parties, based on member state responses to the survey.
According to a presentation at the meeting by Agnès Mathieu-Mendes, Deputy Head of Unit at the commission’s health directorate (DG SANTE), the responses to the questionnaire showed that most member states have transposed into their domestic legislation the directive’s obligation to ensure “appropriate and continued supply” of medicines.
Some countries have included additional provisions, with Denmark, the Netherlands and Poland, for instance, requiring the MAH to provide information on request about the amount of a product that can be delivered, and Sweden and Slovakia placing a specific obligation to supply certain reimbursed medicines. Romania requires the MAH to ensure supplies equal to at least the average monthly turnover of the product over the previous three months.
Manufacturer And MAH Responsibilities
The summary of responses produced by the commission also looks at the responsibilities of manufacturers and the links between, and respective responsibilities of, the manufacturer and the MAH.
In general there are no specific responsibilities for manufacturers, Mathieu-Mendes said, although some member states require obligatory stocks and ensuring continuous supply.
Denmark, France, Lithuania and Poland “either require or expect a contract between the MAH and manufacturer (when these are different companies). In Ireland, MAHs and manufacturers must independently ensure continued supply to patients as they are governed by separate national legislation – a single company may have obligations as a wholesaler, a manufacturer and a MAH.
In some countries (Latvia, Netherlands, Norway and Portugal) manufacturers as well as MAHs are required to notify shortages – in Norway, national manufacturers must report to the authorities, while other manufacturers inform the MAH. Hungary “moderates meetings between different members of the distribution chain in case of shortages.”
As for the obligations placed on drug distributors, most member states oblige them to ensure continued and adequate supply, and in some cases they must supply in quantities/time intervals that meet the needs of patients or meet the needs of a specific geographic area. France requires wholesalers to “respect their distribution territory and public service obligation by holding stock to cover the usual needs of clients for minimum 2 weeks,” according to the commission.
There are differences too in the maximum delivery times permitted: 48 hours in the Czech Republic, for example, and 12 hours in Italy.
Finland has separate legislation for importers of life-saving or essential medicines requiring distributors to hold an obligatory surplus stock (a mandatory reserve supply of 3-10 months’ sales calculated from the previous year's sales). The reason for this law is the “lack of manufacturers of essential medicines in Finland,” the commission notes.
Definitions & 'Critical' Medicines
Most member states said there was no specific definition of shortages or supply disruptions in their national legislation, and that this was done via “internal procedures” or guidance, or was implied from the obligation to notify or from the methodology for determining a “sufficient stock” of medicines.
France defines a product supply disruption as the inability of a retail/hospital pharmacy to dispense a medicinal product to a patient within 72 hours, while Romania “considers a decrease for seven consecutive days of stock at national level” as a shortage alert situation.
In Belgium, a “decision tree is currently in a testing phase with the aim of detecting critical supply problems quickly” – European Commission
As for “critical” or “essential” medicines, 13 member states said they did not have specific legal or regulatory measures for such products, while six did – these included buffer stocks or specific legislation/special monitoring for life-saving or essential medicines, according to Mathieu-Mendes.
In Belgium, a “decision tree is currently in a testing phase (till mid 2018)” with the aim of detecting critical supply problems quickly, according to the commission’s summary. “By following the different steps of the decision tree one is able to decide if alternative medicines are available. If not, other solutions are sought. When the outcome shows that there is no alternative medicinal product available additional information about the supply problem is published. Flagging of shortages affecting critical or essential medicines is being considered.”
In Germany, products classified as critical contain “essential active substances which are subject to special regulatory supervision due to an increased supply risk,” and special monitoring by the authorities is required, in particular where there is only one MAH or manufacturer responsible for batch release, or only one manufacturer of active substances is available.
The definition of a “critical or essential” medicines likewise varies across the EU, with only five having their own definition. France defines critical medicines or therapeutic classes as those for which disruption of treatment is “life-threatening or irreversibly progressive, or without which the patient could be severely harmed.” Italy, Latvia, the Netherlands and the UK refer to the definition of “critical medicinal product” that was adopted by an European Medicines Agency working group on shortages in 2013. The EMA is currently looking at ways of improving the procedures for potential shortages of "critical" medicines caused by non-compliance with good manufacturing practice. (Also see "EMA Taking Steps To Mitigate ‘Critical’ Product Shortages Due To GMP Problems" - Pink Sheet, 6 Apr, 2018.)
In some cases, medicine shortages are caused by exporting (often by wholesalers selling to higher priced markets). Member states were asked whether they had any export restrictions in place to mitigate shortages or the risk thereof: 16 said they had no specific restrictions, while 11 said they did.
Discontinuations
As for what member state authorities did when told of an MAH’s plans to discontinue marketing of a drug, most said they would initiate a dialogue with the company. Portugal has a dedicated working group on supply discontinuations, while France says that essential medicines “cannot be withdrawn from the market until an alternative solution has been identified” and requires “notification of cessation at least one year in advance” for these products.
For its part, Greece checks potential alternative stocks of medicines belonging to the same therapeutic category, and contacts companies marketing alternative medicinal products “in order to communicate the problem and ask for potential increase of production and product stock.”
From the editors of Scrip Regulatory Affairs.