Melanie-Rose Brown, senior director of regulatory affairs at Clinigen, discusses the pre-empting and preventing the shockwaves of drug shortages.
Drug shortages happen. Despite industry’s best efforts to establish and maintain robust supply chains, shortages must be considered ‘expected events’ and increasingly our regulators require us to be ready to respond.
The European Medicines Agency (EMA) monitors critical medicine shortages that might lead to public health crises and is involved in mitigating them by working with the EU Member States and the European Commission. The growing importance of drug shortage issues within the EU is further underlined by the recent proposal from the Directorate-General for Health and Food Safety of the European Commission for a Critical Medicines Act (March 2025), with the aim of increasing access to medicines of common interest, such as those for rare diseases and those not available uniformly across European markets.
European Marketing Authorisation Holders (MAHs) have an obligation to maintain supply of their products once these are commercialised – failure to maintain supply must be reported. The impact of a shortage is complex and costly for MAHs.
Not only can a shortage cause reputational damage to the MAH with Healthcare Providers and Agencies, but it can drive Healthcare Providers to competitor products, resulting in a loss of sales and market share. Mitigating impact on the beneficiaries of the drugs requires cross-functional resource to implement temporary changes to supply chain activities, as well as regular communication to agencies and Healthcare Professionals.
Changes in packaging are also often required. The company may need to implement additional pack manipulation, such as over-labelling and re-packing, to supply an alternative medicine to the market. This comes with the complexity of ensuring sites conducting activities are appropriately authorised and modified batches are recertified.
Beyond this, increased scrutiny of MAH activities is an ongoing impact, with a higher potential for risk-based inspection. In this context, we explore how regulatory engagement can better position industry to respond to shortage scenarios through planning, prediction and communication.
Plan
The EMA provides guidance for MAHs, wholesalers, distributors and manufacturers to help ensure continuity in the supply of human medicines. Within this, the development of shortage prevention and mitigation plans is an important tool to help reduce the likelihood and impact of shortages for marketed medicines.
‘Good practices for industry for the prevention of human medicinal product shortages’ (2023), states that MAHs should have in place a shortage prevention plan for any medicinal product for human use they place on the market, however industry uptake is inconsistent. In the simplest terms, the plan should identify potential risks in the supply chain and set out the measures to manage those risks, to then establish mitigations to address potential or actual shortages for marketed medicines. The focus throughout should be limiting the impact a shortage has on patients. Pivotally, MAHs, manufacturers and wholesalers should each have a plan in place specific to their role.
It is important to note that though this is ‘good practice’ at the European level, appropriate planning is mandated by some national agencies. For example, the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) requires Shortage Management Plans for products of major therapeutic interest. The agency has a clear framework to define the criticality of the medicinal product, the potential impact of shortage on the patient, identification, monitoring and control of risks in the supply chain, stock levels which trigger communication to the authority, and potential mechanisms to prevent shortage and ensure continuity of patient treatment.
The holistic nature of shortage prevention and mitigation planning requires a detailed understanding of the supply chain, the commercial requirements of the market and the position of the medicinal product within the wider therapeutic area. It’s critical to involve Regulatory Affairs in this planning stage to ensure that the proposed mitigation strategies are feasible in the context of agency expectations and requirements.
Predict
It can be tempting to believe that if supply chain is ‘working as it should’, shortages will not happen – but the evidence within the global pharmaceutical industry says otherwise. Shortages can originate from any point of the supply chain but there are likely triggers:
- Activities with planned stock-building to manage transition (change in API or drug product manufacturing site; transition of ownership to new MAH);
- Sourcing of materials from territories with political instability;
- Products with low volume (i.e. rare or ultra-rare disease);
- Products with complex presentations (i.e. co-packaging of multiple components).
Realistic planning around these triggers and leveraging regulatory mechanisms can eliminate or limit the impact of shortages. Early discussions with the Regulatory Affairs function to define submission strategy, requirements and timelines will increase the likelihood that shortage can be avoided during transition periods. A regulatory plan will establish the timelines to acquire any data, conduct agency meetings, author and submit a dossier and support the procedure through to approval - sharing this with the cross-functional team will develop a more realistic timeline to achieve the desired change and enable a more accurate stock-build plan. Where it is not possible to prevent risks, a frank discussion with the Regulatory Affairs function can enable MAHs to request an expedited review from the relevant agencies and consider appropriate commitments to manage a limited data package or at-risk implementation of certain changes to manage lead times.
Communicate
At the core of a strategic response to a drug shortage is honest, straightforward and consistent communication. This includes diverse stakeholders within the MAH and manufacturer companies, but also regulatory agencies and healthcare professionals.
Reporting structures for drug shortages have become more regimented, both with the EMA and National Regulatory Agencies, with many agencies implementing specific reporting platforms and making shortage information readily available to the public.
The advice is simple: inform authorities of potential or actual shortages as early as possible and provide detailed information to predict impact and implement preventive measures. In reality, the requirements of each national authority are different, and a detailed understanding is required to ensure that these communications are timely, directed appropriately, and provide the required outcome: continued patient supply. In this context, the Regulatory Affairs function becomes a key stakeholder to define and implement communication strategies.
For example, the timelines required for notification of a temporary cessation of supply differ from market to market. In Italy, the requirement is notification four months prior to potential shortage, with the possibility of fines if this is not followed. In contrast, Finland requests a minimum of 2 months’ notice, and for products that require a shortage management plan in France, the plan must be followed otherwise penalties may apply. Awareness of these different agency requirements is necessary to maintain compliance during an emerging shortage.
The role of regulatory affairs
The Regulatory Affairs team is a key contributor for planning for shortage scenarios and mitigating those that occur. As a compliance and a strategic function within the pharmaceutical industry, Regulatory Affairs serves both the patient and industry by understanding the mechanisms available to ensure continued supply and being responsive to the changing regulatory landscape that governs MAH responsibilities.