This article discusses how the EU is currently addressing medicines shortages in non-emergency times and explains the obligations of marketing authorisation holders (MAHs) in relation to potential shortages. See part two for a review of the EU's proposals for managing medicines shortages in the future.
Identifying medicines in short supply: MAH obligations
The first step for managing supply shortages is to identify them.
Notification by MAHs
EU legislation requires MAHs to notify the European Medicines Agency (EMA) via the European Shortages Monitoring Platform (ESMP) of shortages of (Regulation 2022/123, Article 10):
- centrally authorised products when they become aware of a potential or actual shortage in one or more EU Member States, and all new information regarding the same
- human medicines notified by the EMA's Medicine Shortages Steering Group (MSSG) as being subject to 'a preparedness action' and which might be either a centrally or nationally authorised product.
The MSSG has so far issued shortage notices on GLP-1 receptor agonists, and on specific antibiotics.
Separately, there legal obligations requiring that MAHs and distributors "ensure appropriate and continued supplies ….so that the needs of patients in Member States are met" (Article 81, directive 2001/83/EC) and the MAH must inform the Competent Authority in the relevant member state if a product permanently or temporarily "ceases to be placed on the market…no less than two months before the interruption" (Article 23a, Directive 2001/83/EC and Article 13 and Article 38, Regulation 726/2004). These obligations apply whatever the reason for the interruption or cessation in supply, even if there are regulatory or quality issues of which the competent authorities are aware. Reporting of supply issues to competent authorities involves reporting to each country separately via the relevant competent authority website.
The guidance goes wider and requests, but does not oblige MAHs to report all potential or actual shortages (defined simply as a 'disruption of supply'/'where supply does not meet demand at a national level') to national competent authorities (NCAs) as soon as possible. Note that this relates to a disruption but not a cessation of supply, with the latter being subject to legal obligations to notify. The guidance states that reporting should be made of: (a) all shortages currently affecting on or more EU member states; and (b) all impending/ anticipated shortages expected to affect one or more EU member states.
The EMA guidance states that the MAH should be particularly vigilant in relation to medicines for which "no or only limited alternatives are available, and where interruption of supply will result in a potential risk to public health". MAHs are urged to be particularly mindful of situations where there is a single manufacturer supplying the product to multiple MAHs. All are expected to continually assess supply information against demand and to develop shortage prevention and response plans.
Additional MAH obligations on supply interruptions
MAHs for all human medicines authorised in the EU must appoint an industry single point of contact (i-SPOC) which they register via the IRIS platform. These persons then directly inform the EMA about the supply and availability of critical medicines identified in the context of a major event or a public health emergency. The MSSG uses these contacts for rapid, two-way communication with the MAHs of medicines in the critical medicines list.
MAHs are requested (but again, not obliged) by the guidance to have shortage prevention and management plans, quality systems to increase resilience of the supply chain, and to promote fair and equitable distribution to meet patient needs. The latter is not straightforward to achieve, particularly with specific language requirements for the labelling of medicines in individual countries.
The Critical medicines list
The Critical Medicines List is maintained by the MSSG. Medicines are deemed critical based on the seriousness of the disease the medicine targets and on the availability of suitable alternative medicines. These can be any type of medicine for human use: innovative or generic and can include vaccines. The EMA's Q&A document describes the list as one of medicines for human use "for which continuity of supply in the EU is a priority". These medicines are subject to close monitoring by EMA committees. However, the precise obligations for MAHs are yet to be fully defined.
EMA activities
There is a lot written by the EU on supply shortages, partly driven by the fact that there are several groups involved in the strategy to address shortages, mostly overseen by the EMA. These groups are described below to give a sense of the operations behind the EMA strategy and to demystify communications that MAHs might receive on the subject of shortages.
- Executive Steering Group on Shortages and Safety of Medicinal Products or, for short, Medicine Shortages Steering Group (MSSG). It establishes lists of medicines for emergency care, surgery and intensive care, as well as the list of critical medicines. Its role is to monitor, report on shortages, and recommend actions to manage supplies where necessary. Member states, the Commission, the EMA and patient groups are represented on this committee.
- The Medicine Shortages Single Point of Contact (SPOC) Working Party provides recommendations to the EMA on monitoring and management of medicines shortages. Its role is to improve information sharing between EU Member States, the EMA and the European Commission on important medicine shortages of human and veterinary medicines, and to coordinate actions to help prevent and manage shortages. Members are drawn from national competent authorities and the SPOC is chaired by the EMA's Head of Supply and Availability of Medicines and Devices Service.
- The MAH/EMA Joint Task Force on Availability of Authorised Medicines for Human and Veterinary Use provides strategic support and advice for coordination and a concerted approach on the availability of the medicinal products authorised in the EU in 'peace time', ie, non-emergency situations. Their focus is on products which are not or no longer marketed and supply chain disruptions, in both cases in relation to authorised products. They have developed the following three guidance documents for MAHs: guidance for MAHs on preventing shortages, guidance for MAHs on detecting and notifying shortages and guidance for industry on implementing shortage prevention plans.
