Background

The European Medicines Regulatory Network (EMRN), as well as other international organizations, have warned that medicine shortages have become a problem of global reach. Since 2016, the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have set up a working group that has been tasked with studying medicine availability issues in Europe.

As a result, the EMA has published a report on good industry practices for the prevention of stockouts of medicines for human use. This document specifies recommendations on best practices to be followed by marketing authorization holders, wholesalers, distributors and manufacturers in order to ensure the continued supply of medicines and, at the same time, reduce the impact of stockouts.

Scope

The EMA report sets out recommendations to prevent potential shortages of medicinal products for human use and to mitigate such shortages in case they occur. The document focuses on outlining the common causes of medicine shortages in a non-exhaustive manner without being an unequivocal interpretation of European Union legislation.

Although the document focuses on marketing authorization holders, wholesalers, distributors and manufacturers, its content covers all the agents involved in the medicine supply chain. It should be noted that the supply chain includes various parties that have legal obligations to ensure the continued supply of medicines to patients. Even so, issues related to commercial activities are not included in the scope of the report.

Best practices recommendations

For situations where it is not possible to meet the demand for medicines at national level, the EMA has developed recommendations to mitigate the negative impact of medicines shortages in the supply chain.

The proposed strategies seek to address the underlying causes of shortages by introducing shortage prevention as an additional part of the medicines lifecycle. These strategies are compatible and not mutually exclusive and can therefore be implemented together. It should also be recalled that the fight against medicines shortages is also part of the European Commission's pharmaceutical strategy, which encourages international collaboration and the development of proposals and strategies to combat shortages. In particular, preventive and palliative strategies that seek to take advantage of the information available to ensure the continuity of supply of medicines to patients and health systems, with the advantage of knowing the results in advance.

In total, 10 recommendations have been made, which are listed below:

• MAHs, manufacturers and wholesalers, should notify the National Competent Authority of a potential or actual shortage as soon as possible in advance of any shortage: Potential stockouts should be reported at an early stage. Updates on stockouts should be reported in a timely manner to allow for a reassessment of the impact of the stockout, as well as the resumption of supply.
• Increase transparency relating to shortage information: There is a need for increased communication and knowledge sharing between stakeholders, taking into account competition law.
• MAHs should increase the accuracy of notification detail provided: Notifications should provide all available information requested in the form to allow understanding of the situation, assessment of the impact and consideration of appropriate measures.
• MAHs, manufacturers and wholesalers, should each have a shortage prevention plan specific to their role: A prevention plan provides a structured framework within the pharmaceutical quality system to avoid stockouts. It has to be adapted in each case depending on whether the producer is a manufacturer (it covers from manufacture to marketing) or a wholesaler (it covers from receipt to delivery).
• MAHs, manufacturers and wholesalers should each have a shortage management plan to respond to issues resulting in shortages: A shortage management plan identifies signals and risks to the continued availability of the product. It also implements a procedure for their prevention or mitigation. Its efficiency should be evaluated on a regular basis.
• Optimize pharmaceutical quality systems to strengthen the reliability and resilience of supply chains throughout the lifecycle of medicine: The pharmaceutical quality system should be adapted to include assessment of the robustness of the supply chain and the controls in place. The principles of the specific guidelines for improving the good manufacturing and distribution practices environment and post-authorization changes to strengthen the reliability of supply chains should be applied.
• Increase resilience in the supply chain, taking into account known vulnerabilities: Whether the supply model is justifiable must be assessed and documented. Sufficient contingency must also be ensured to deal with unforeseen delays during changes in the manufacturing site or transfers of ownership.
• Improve communication between stakeholders: Cooperation between the marketing authorization holder and the manufacturer is necessary, as well as the existence of communication systems between the both of them. Key processes and supply chain maps must be identified. A criteria-based system for communicating potential supply disruptions should be developed. Any changes in demand for medicines must also be taken into account.
• Promote fair and equitable distribution to meet the needs of patients: No more stock than usual should be dispensed when shortages exist. In addition, in case of shortages, the allocation of stocks between countries should take into account the clinical needs of patients.
• Take appropriate steps to minimize the risk of parallel trade or export exacerbating shortages: Decisions on restrictions to parallel trade in medicinal products must be justified and proportionate. In situations of critical shortage, companies involved in such trade should monitor the situation and inform the authorities of the exporting Member State.

Final considerations

In short, the various recommendations made by the EMA include the optimization of stockout notifications and the improvement of the accuracy of the details provided in these notifications, the development of stockout prevention plans, the optimization of the quality system and the increase in the resilience of the supply chain, among other measures. In addition, the document is complemented by other international initiatives such as the European Commission's Pharmaceutical Strategy and the European Single Point of Contact (SPOC) network.

In this sense, pharmaceutical companies that are part of the distribution chain of medicines should follow these recommendations reviewing and adapting their internal procedures in order to help prevent shortages of medicines.

For more information, the full text of the EMA report can be found here.