Based on the member states’ responses to the rare but severe side effects of the AstraZeneca COVID-19 vaccine, one might be tempted to believe that there is no common approach to enforcing European Union (EU) medicines policy. In this post, the fourth in a special RENFORCE Blog series on the enforcement of EU law, Laurens van Kreij takes a more nuanced look at medicines policy’s complexities, and explains why the national responses were able to diverge so strongly. He thinks the chances of rapid and major change are slim.
The ongoing campaign to vaccinate people for the prevention of the coronavirus disease is fascinating: never before have so many people been vaccinated in such a short period of time – laboratories developed highly innovative vaccines in a matter of months, manufacturers reproduced them in billions, and public authorities used the quickest possible procedures for their licensing. The vaccination campaign, however, is not a complete success. Particularly infamous is the AstraZeneca COVID-19 vaccine, and not least because this vaccine may cause 1 in 10.000 recipients to experience a combination of blood clots and low levels of blood platelets. As of 4 April 2021, over 200 people – particularly women under the age of 60 – experienced such severe adverse reactions, and many of them died as a result.
In the European Union (EU), the response to these severe side effects was chaotic. Although the AstraZeneca vaccine initially obtained a single license from the European Medicines Agency (EMA) and the Commission, the member states – all part of the same internal market – responded differently once its serious side effects came to surface. Its use was first suspended in a small number of member states only (e.g. Austria, Denmark); other member states initially continued to administer the vaccine but later changed course (e.g. France, the Netherlands); and yet another group would never halt its use (e.g. Belgium, Poland). The situation became even more remarkable when Denmark definitively ceased or considerably limited vaccination with AstraZeneca, while the EMA deemed AstraZeneca’s vaccine safe enough to remain on the market.
One may be tempted to think that the common approach to enforcing EU medicines policy is dysfunctional, if not entirely absent. After all, the vaccine was repeatedly approved by the EMA and the Commission, yet all respective member states themselves decided whether or not to suspend its use. In this post, I take a short but more nuanced look at the EU’s regulation of the medicines market. I argue that the mechanism for medicines policy enforcement is an intricate mix of decentralized as well as centralized components – as is EU medicines policy more broadly. I develop the argument in two stages. First, I demonstrate that not only enforcement, but also initial licensing relies heavily on the input and consent of the member states. In the second part, I argue that the role of EMA in the enforcement of medicines policy is greater than the chaotic handling of AstraZeneca’s vaccine suggests – but that the peculiarities of the medicines market don’t allow a more concerted, EU-wide response.
The initial licensing of medicines
The case of AstraZeneca suggests that the enforcement of EU medicines policy – including the response to potentially unsafe vaccines – is the domain of the member states proper. Also the initial licensing of medicines, however, has strong decentralized features; the national medicines authorities are key to all three EU procedures that regulate medicines’ market access.
The role of the national medicines authorities is perhaps most visible in the mutual recognition and decentralized procedures. In the mutual recognition procedure, manufacturers can have their initial marketing authorization recognized by other member states, so as to progressively enter other national markets. And in the decentralised procedure, manufacturers apply for an initial marketing authorization in several member states at the same time: upon satisfying the right conditions, a manufacturer obtains licenses for every jurisdiction involved. In either of these procedures, it is thus clearly the national authorities that assess the quality, safety and efficacy of a medicinal product; the EMA – established in 1995 and ‘responsible for coordinating the existing scientific resources put at its disposal by the competent authorities of the Member States for the evaluation and supervision of medicinal products’ – only comes in in case of conflict, and even then, the arbitration panels are composed of the national competent authorities themselves.
AstraZeneca’s COVID-19 vaccine was licensed using yet another procedure: the centralised procedure. In contrast to what the name suggests, the national authorities are also essential to this procedure: although it leads to a single license for the entire internal market (which is formally issued by the Commission on the basis of an EMA opinion), it is again the national competent authorities that assess the quality, safety and efficacy of a medicine. When a manufacturer submits an application for a central marketing authorization, one or two national authorities conduct the factual assessment of the dossier. And after they jointly share their findings with the other national competent authorities convening in EMA, all national authorities vote on the application, after which the vote becomes a single EMA opinion that is submitted to the Commission. In the default situation, the Commission then convenes a panel of (again) national experts to perform some last checks, and – if all goes well – the EMA opinion becomes a centrally-issued marketing authorization.
The enforcement of medicines policy
As indicated earlier, the chaotic response to the serious side effects of the AstraZeneca COVID-19 vaccine suggests that the enforcement of EU medicines policy has no central elements at all. After all, each member state went its very own way when the AstraZeneca vaccine was first associated with blood clots and low levels of blood platelets.
Yet also when it comes to enforcement, the picture is more nuanced. Above all, it is the EMA and the Commission that ultimately decide on the withdrawal, suspension or amendment of a centrally-issued marketing authorization – no national medicines authority is capable of doing so on its own. All information about side effects is collected by the national authorities on behalf of EMA, and submitted to its office in Amsterdam for further assessment.
What happened, then, when every member state responded differently to the AstraZeneca vaccine’s serious side effects? One crucial ‘decentral’ characteristic of EU medicines policy enforcement is that member states can trigger an emergency brakeand temporarily suspend the use of a particular medicine, ‘when urgent action is essential to protect human health’. Following the exact wording of this provision, member states indeed triggered this emergency brake when they received reports on severe side effects and decided to suspend the use of the AstraZeneca vaccine. Yet in this case too, a final decision is to be taken by the Commission on the basis of an EMA opinion. And it was exactly such a decision that was taken on 8 April 2021: the AstraZeneca vaccine was safe enough to remain on the market, although its marketing authorization was changed to reflect the very small risk of blood clots and low levels of blood platelets in the patient safety information.
The peculiarities of the medicines market
How is it possible, then, that many member states now use the AstraZeneca vaccine only for people over 55 or 60 years old, while Denmark even decided to stop using it altogether? Isn’t that precisely what a final EMA and Commission decision aims to prevent?
Although indeed at odds with the objective of uniform EU medicines regulation, such changes in vaccination strategy may very well survive legal scrutiny. The crux is that the member states are not merely vaccine co-regulators, but also the only vaccine buyers. As in the world of medicines more generally – in which the actors shaping medicine demand need not be the ones to use them – the current vaccines are not bought by citizens themselves, but by their governments. That explains why member states may limit the use of AstraZeneca’s vaccine in their vaccination campaigns without running the risk of legal repercussions: while member state regulators can indeed not legally restrict the marketing of a vaccine as it was approved by EMA and the Commission, national governments can – as the exclusive buyers of the AstraZeneca vaccine – simply choose no longer to buy and administer them.
The AstraZeneca COVID-19 vaccine demonstrates that the specific characteristics of a market can be of great influence on the functioning and outcomes of an enforcement system. That lesson, however, is of no avail to the European citizens left puzzled. Why is the AstraZeneca vaccine still in use in member state A, whereas it is no longer administered in member state B? Why do levels of human health protection differ within the EU? However appropriate such critique and the potential of further centralization, the chances of rapid and major overhaul are slim. The constitutional framework is tight when it comes to the EU’s involvement in healthcare affairs, and also secondary EU medicines law has proven to progress incrementally rather than all of a sudden.