Shortage management/shortage prevention plans for Pharmaceutical Medicines

Why do shortages occur?

There are several reasons which include commercial, distribution, unexpected increased demand, natural disasters, regulatory, quality and manufacturing issues.

From 2016 – 2020, Quality and manufacturing issues reportedly caused 48 – 58% of shortages. Manufacturing related shortages vary widely and can arise for many reasons such as capacity issues, shortages in raw material, Active Pharmaceutical Ingredients (APIs) or components, factory closures and many more.

Examples of Quality issues are Out of Specification results, deviations or adverse events. These prevent batch release and can lead to market recalls unless the risk to the patient of recalling a batch is more harmful than allowing it to stay on the market.

Over the last few years, manufacturing and supply chains have become more and more complex. This added complexity often results in added risk or an increased number of changes. Changes, which need to be submitted as variations to Health Authorities, can lead to shortages due to the time involved in the approval process.

Natural disasters like the Covid 19 pandemic presented serious challenges globally and exposed major vulnerabilities in pharmaceutical supply chains and the availability of medicines. The list goes on.

What are the requirements for notifications within EU law and what is the role of the regulatory bodies?

Article 23a in Directive 2001/83/EC describes the requirement for Marketing Authorisation Holders to notify Health Authorities of shortages including the timeline requirements.

Article 13 of EU GMP Directive 2017/1572 defines the legal requirement for a manufacturer to inform the competent authority and if applicable the MAH of any defect that could result in a recall or abnormal restriction on supply.

Regulation (EU) 2022/123 and Heads of Medicines Agency (HMA) 2023 Guideline ‘Good practices for industry for the prevention of medicinal product shortages’ resulted from the disruptions due to the Covid 19 pandemic. The regulation describes a reinforced role for the European Medicines Agency in ‘crisis preparedness and management for medicinal products and medical devices’. Different bodies, namely the Medicines Shortages Steering Group (MSSG), the European Shortages Monitoring Platform (ESMP) and the Single point of Contact (SPOC) Working Party all work together to manage shortages using a harmonised and risk based system.

As all shortages have different impacts, a thorough evaluation needs to be performed to assess the criticality of the disruption. Availability of alternative medicines, the therapeutic indication, extent of shortage and reason for shortage are some of the aspects to be considered so the mitigations can be agreed in a proportionate manner.

In March 2025, the EU Commission has put forward proposals to update the pharmaceutical legislation in the form of the Critical Medicines Act (CMA) to improve the supply of critical medicines in the EU. The CMA also has an objective of improving access to other medicines such as those to treat rare diseases and to make some medicines more available in certain markets.

Some of the key features of this act are strategic projects for critical medicines, which strengthen the access to funding and reduces timelines for procedures, public procurement, collaborative procurement among different member states, international partnerships and state aid guidelines for financial support of member states. All of these measures aim to support the resilience of supply chains, improve accessibility and add back-up options to reduce dependencies on single sources. The focus is on critical medicines but other medicines are also considered and assessed depending on the patient needs and area of therapy.

Role of Health Products Regulatory Agency (HPRA)

The HPRA also has a strong role in the prevention and mitigation of medicine shortages. As clearly stated on their website, pharmaceutical companies must inform them when they are aware of shortage or a potential shortage. HPRA maintains an up to date list of medicines shortages impacting the Irish market and a weekly update on this is issued to stakeholders. This information is sent to all subscribers to HPRA’s My Alerts.

In situations where regulatory flexibility can reduce a supply problem without impacting patient safety, HPRA takes action to alleviate gaps in urgent medicine supply for example by allowing flexibility on labelling or accelerating approval in certain situations.

These aspects form part of a medicines shortages framework, which is co-ordinated by HPRA. The framework explains procedures for notification, evaluation and communication of shortages and the roles of the various stakeholders such as Marketing Authorisation Holders (MAHs), Manufacturers, Wholesale distributors, Healthcare professionals, Health Service Executive (HSE) and patient representatives.

Risk Based Approach by Manufacturers/ MAHs

A Risk Based approach is essential for management of drug shortages by MAHs and this requires a consistent effort to review complex issues by a cross functional group with diverse areas of expertise. Manufacturers must proactively review risks arising from several aspects including equipment, processes, facilities, product issues and stability.

A robust Pharmaceutical Quality System (PQS) is fundamental to ensure compliance with regulations. A thorough understanding of manufacturing and distribution is essential to prevent possible shortages. Quality oversight of Contract Manufacturing Organisations and laboratories in the Supply Chain is important to maintain control of the compliance of these separate entities. This risk based focus is in line with ICH Q9 R1 Quality Risk Management, which defines harm as ‘damage to health including damage that can occur from loss of product quality or availability’.

Role of the Qualified Person

The Qualified Person also has a responsibility to ensure the ongoing supply of medicines to patients. In addition to ensuring that medicines reaching the public comply with the requirements for quality, safety and efficacy, the QP also needs to consider making them available on a consistent basis.

Conclusion

The shortage of medicines is viewed as a very real concern in today’s world of pharmaceutical supplies but with the increased focus by the health authorities and ongoing collaboration of all the stakeholders, these shortages can be minimised.