When We Work Together, Hand in Glove with Our Partners, We Can Overcome Any Barrier: A Conversation with EMA's Emer Cooke

FROM A GLOBAL PERSPECTIVE

By Emer Cooke, EMA Executive Director

June 4, 2024

Emer Cooke has been Executive Director of the European Medicines Agency (EMA), the European Union’s (EU) medicines regulator, and the chair of the International Coalition of Medicines Regulation Authorities (ICMRA) since November 2020. She qualified as a pharmacist from Trinity College, Dublin, Ireland. Her passion for international cooperation and harmonization has led to a 30-year career in medicines regulation in a variety of roles at European and international organizations including the European Commission and EMA, where she previously held roles as Head of Inspections and Head of International Affairs. Emer was the Director responsible for all medical product-related regulatory activities at the World Health Organization (WHO) in Geneva immediately before taking up her current role.

Thank you for agreeing to talk to FDA. Let's begin by saying a little bit about what the European Medicines Agency does. What are EMA’s responsibilities or its remit?

It is a real pleasure to get the opportunity to talk to you but also to explain what EMA does. Let me put my answer into the context of the FDA. Just like the FDA, EMA is responsible for protecting public health by regulating human and veterinary medicines. We also have a role in the oversight of medical devices in the European Union, but not to the same extent as the FDA. I would also like to clarify that in Europe the term ‘medicines’ includes both drugs and biologics — so vaccines, for example, are considered medicines. Unlike the FDA, we are not responsible for food, cosmetics, or tobacco products.

When it comes to the regulation of medicines, the biggest difference between us and the FDA is that we work as a multicountry regulator. We regulate a market made up of 27 countries and more than 450 million people who speak 24 different official languages. EMA operates as a network with national competent authorities in each of those 27 Member States.

When we regulate medicines, we work together with scientific experts across this network to make sure that European citizens and animals have access to safe, quality, and effective medicines. We coordinate the evaluation of medicines across the EU, bringing together the best expertise from the Member States to ensure that EU citizens can rely on excellence in scientific assessments, no matter where they are based. Whether they are in one of the Nordic countries, such as Sweden or Denmark, or in the South — Italy, Spain, or Greece — or, in the former Eastern Bloc countries such as Bulgaria or Romania.

It is important to talk about the success of our network in uniting countries with varying economies and sizes to create a single market for pharmaceuticals. This is possible because we work within a system of reliance and recognition across the EU. For a medicine to be authorized in the whole of the EU, we do not have to carry out 27 separate scientific assessments. Because we rely on the same standards, our principle is: one application, one assessment, and one marketing authorization valid in all 27 Member States. This means we are in a very strong position to promote the concept of reliance on EMA scientific assessments by regulators from outside the EU.

This proved successful during the pandemic when we conducted our 'OPEN’ pilot, where we invited regulators from outside the EU to sit in on our scientific meetings and use the assessments of our scientific committees in their work. In some cases, this translated into quick decision-making in up to 160 countries outside the EU. We are now expanding this concept to non-COVID products, particularly innovative products, and those with potential to address antimicrobial resistance.

This was certainly one of the key lessons from COVID-19 for me: when we work closely with our many partners, we can better address EU-wide or global challenges. As a result of our work during the pandemic, we now have an expanded legal mandate under the EU Health Union, which requires us to collaborate even more with EU Member States and stakeholders. And it has enabled us to lay the groundwork to be better prepared for future crises.

Just to clarify on your remit, does it span across the product life cycle from product development to the postmarket setting?

Yes, it does. We provide developers with scientific advice, which is like your pre-IND (Investigational New Drug Application), and we evaluate and monitor across a product's life cycle, including monitoring of adverse reactions and events, which may lead to modifications of a product’s authorization, a suspension, or a withdrawal.

And do you also inspect manufacturing facilities?
Yes, we inspect for Good Manufacturing Practice and Good Clinical Practice. We work with the Organisation for Economic Co-operation and Development for Good Laboratory Practice, and we also can inspect operators for Good Pharmacovigilance Practice and Good Distribution practice. We do this through our network of inspectors in the Member States.

We’d like to ask you about EMA’s priorities. What do you see as the most important opportunities or challenges for EMA, let’s say over the next five years?

EMA’s single priority is to ensure that patients and health care professionals in the EU have access to safe, quality, and effective medicines. We do this across science, medicines, and health. In the context of the next five years, I see tremendous opportunities for us: the accelerating pace of scientific developments, the volume of data that we use as regulators, and the opportunities presented by digitalization and the use of artificial intelligence.

Obviously, there are challenges too: the management and mitigation of medicines shortages, ensuring sustainability and putting a strong focus on crisis preparedness. I also think that workforce planning and ensuring the well-being of my own staff, and all the experts that work with us, is something we need to get right over the short and long term.

In Europe, we are moving towards more data-driven medicines regulation. For example, we are using real-world evidence to fill information gaps during regulatory procedures through the Data Analysis and Real World Interrogation Network (DARWIN EU). By working with data partners such as hospitals, registries, insurance claims, biobanks, and other sources we can transform data, analyze it and use it to help EMA committees and national regulators make more data-driven decisions on medicines. Between September 2021 and February 2023, we commissioned studies based on requests received from members of EMA’s scientific Committees, Member States, or other stakeholders.

We also need to use these opportunities to enable smarter clinicals trials. Our work to modernize clinical trials in the EU is progressing. Through our Accelerating Clinical Trials in the EU initiative - or ACT EU we are bringing together all stakeholders in Europe’s clinical trial ecosystem – patients, health care professionals, industry, regulators, academia, and Member States. Over the next five years this will result in smarter clinical trials through regulatory, technological and process innovation.

Finally, the single most important opportunity we have over the next five years is the package of draft legislation currently being discussed by EU lawmakers, which effectively reviews the whole framework of pharmaceutical regulation in the EU. We demonstrated during COVID that we can do things differently - with this draft legislation we have an opportunity to build on these learnings and my ambition is to ensure we make that happen.

The combination of our learnings and the input into the implementation of the new pharmaceutical legislation will ensure that our framework is future proof, fit for new and innovative medicines, supportive of better access to medicines for patients, and will help us address major public health threats like antimicrobial resistance and medicines shortages.

So, you have a long history with EMA, serving in key leadership roles such as Head of Inspections and Head of International Affairs, culminating in your appointment as EMA Executive director in November 2020. That was quite a challenging time to take on this role — during a global pandemic. Can you talk about how you approach your role as executive director and how the COVID-19 pandemic influenced your tenure, changed EMA and obviously now is potentially affecting these regulations?

I started working for EMA in 2002, but I have been working on European and international harmonization since 1992. I see the combination of what I have done both at EMA, and in other roles including at the WHO, as fundamental building blocks for how I approached the challenges of COVID-19 as head of EMA.

In the four years before this role, I was the director responsible for regulation of all medical products at the WHO in Switzerland. I had applied for the EMA position in early 2019, long before the pandemic emerged. If I look back now, I feel that my whole career – which spans 35 years in medicines regulation, people management, international collaboration – was preparation for my first years at the helm of EMA during what was, and I hope will be, the biggest public health crisis we will see in our lifetimes.

For me personally this was a huge test, but it was also a test for EMA: for our network, our mission, our people, and our ability to work together in an agile and responsive manner. This was a new job for me, and of course I wanted a new challenge, but I did not expect the challenge that I got on my first full day as Executive Director.

That was November 16, 2020, and we were heading towards our first Christmas lockdown. We had hospitals overrun with critically ill patients, thousands of people were dying every day, and we were just beginning to see the first good clinical results from the COVID-19 vaccines trials. We had a huge responsibility as a medicines regulator to make sure that we were doing the right thing — ensuring that vaccines were safe, effective, and of high quality. And I have to say, it was incredibly rewarding and motivating.

This experience has changed the way I look at things, but it has also changed the way that EMA does things. The EMA that entered the pandemic is not the same EMA that left it. Over the course of the pandemic, we really had to move beyond the formal boundaries of our mandate. We had to respond and adapt as an organization and do things that normally we would have said, “that’s not for us.” Quite simply, if we didn’t take the lead role and coordinate across our network, it wouldn’t have been done.

This brought a range of new tasks to our door that we had to develop effectively on the fly. For example, crisis coordination and medicine shortages were not formally part of EMA’s role in Europe. We also had to play a much bigger role in communicating directly to patients and citizens.

What makes me incredibly proud is that, when faced with a serious health crisis, our system did not just go through the motions, it went into overdrive to deliver. I can talk about this from inside the room because I was there making the decisions, working with our partners, helping our citizens and it is still a source of great pride, hope and inspiration. The lessons of COVID-19 are clear: we can achieve anything when we collaborate. When we work together, hand in glove with our partners, we can overcome any barrier.

Could you tell us more about the regulations now under consideration that address what you learned during COVID?

EMA has done a thorough examination of its COVID-19 response and published the lessons we have learned. We know we have an opportunity to combine what we learned, in terms of agility, with the availability of a lot more data to help us in our decision-making.

There is massive potential in doing things differently, allowing us to work smarter — not harder — and through doing some reverse engineering, based on our experiences. For example, we can use data analytics and digitalization to take away some of the manual and administrative work and bring our focus to more valuable activities, such as assessing the real benefits and risks of the products that we regulate.

During COVID, we learned to accelerate our processes, with rolling reviews, which is something that FDA has been doing effectively for years. In Europe, our normal approach was to wait until the complete package of data was available before we started the assessment. During the pandemic we were looking at pieces [of the package] as the data became available – and we were reviewing it in real time.

We also used a lot more real-world evidence. For example, we were able to respond very quickly to rare adverse events, identified through the signal management process for one of the COVID vaccines and we were able to contract a study to see what was happening in different patient groups. We then used this to look at the population: could we see whether children were more affected, or males or females? Which age groups?

As I mentioned, we now have a program in place which, strengthened by our new regulation, allows us to perform studies to address various questions raised by our scientific committees on issues like the geographic distribution of certain diseases, how medicines are prescribed and used, what actual impact they have, and how they fit in the standards of care and our health systems in the EU.

Through DARWIN EU we can look at prescription patterns of antibiotics, which then allows us to optimize the use of certain antibiotics and try to avoid antimicrobial resistance. Another study conducted using real-world evidence characterized the use among girls and women of anti-epileptic medicines containing valproate. These are some of the questions we can answer now using real-world evidence. This is about doing things smarter and using technology, data, and digital tools to help us become more efficient and improve the work experience for the people who are doing the work.

We'd like to pivot now and ask you about the FDA-EMA partnership. Can you share your thoughts on the value of that partnership and what are some significant highlights or achievements that come to mind?

We have a very long-standing relationship with the FDA. Last year, we marked the 20th anniversary of the signature of our confidentiality arrangements. The EU-FDA relationship goes back even longer.

Back in 1998 when I worked at the European Commission, I was responsible for engaging with the FDA, and the relationship has changed quite dramatically since then; there is much more collaboration and communication. We have built a lot of trust between our scientific experts, and we understand that we face the same challenges, we have many of the same products, and both of our organizations are committed to serving our respective patients.

This trust was developed by getting our scientific leads together into working groups we call ‘clusters.’ Oncology was the first cluster, set up in 2004. Scientific experts from both organizations would come together to discuss the products they were looking at, the challenges they found in assessing the data and try to see if there was a common approach.

That first oncology cluster has led to new clusters in other areas: we now have more than 30 clusters in place between EMA and FDA. Some of them have expanded beyond FDA to include scientific experts from other regulatory agencies, who saw the success of these clusters and developed an appetite to get involved.

We have involved additional regulators in our clusters if we both have confidentiality arrangements with them. The clusters range from: pediatric medicines, rare diseases, orphan medicines, advanced therapies, pharmacovigilance, real world evidence, patient engagement and Good Clinical Practice inspections and allow experts from both agencies to exchange information and have robust scientific and regulatory discussions. We learn from each other, we build trust, and it helps us advance towards a convergence of approaches.

I also want to mention a couple of other areas that I think have been incredibly valuable in building the EMA-FDA partnership. There is, of course, the mutual recognition agreement between our two agencies, which allows us to rely on each other’s inspection of manufacturing facilities. This is a testimony to strong partnership and helps us make the best use of our limited inspection capacity. If we rely on each other’s inspections, we can increase the number of manufacturing sites that are being inspected overall, giving patients on both sides of the Atlantic reassurance that they can rely on the quality, safety, and efficacy of their medicines.

One area that might not be known to readers is the possibility of providing parallel scientific advice to companies in the development phase. We also can exchange information on ongoing assessments, post authorization and pharmacovigilance. A recent development has been in the area of shortages of specific products, where we have been able to share our experiences and ideas for mitigation strategies.

I also would specifically like to mention our liaison program. We have an EMA liaison based in the U.S. and an FDA liaison based in our offices in Amsterdam. This exchange of permanent staff really gives us an insight into how our different agencies work: they point us to opportunities for greater collaboration and help identify problems that we may not know are there.

Another area of progress is our fellowship program where we send colleagues, on a short-term basis, to the FDA to focus on a particular area that we are trying to develop and want to learn from their experience. Or it might be an area where we know international challenges exist and we think that if we get people together, we might get to the root of it and see how best to address it. All of this is enabled by our confidentiality arrangements and our extensive experience working together in a trust-based relationship.

The FDA and EU health officials from DG SANTE, the EMA, and the European Food Safety Authority recently participated in a bilateral meeting at the FDA’s headquarters at White Oak. Do you have any takeaways from that?

I am very happy to talk about our recent meeting. It was preceded by a visit from FDA Commissioner Califf and his team in late February, which really paved the way for what was our first face-to-face bilateral in four years. We used to have bilaterals every year, but they were postponed due to the pandemic and other challenges.

A big thank you to FDA for hosting this year’s meeting. We were impressed with the thought and organization that went into this bilateral and we were able to field quite a large delegation from the EMA side. We discussed areas such as artificial intelligence, the one quality issue, advanced manufacturing and how we can look at evidence generation to support better clinical trials. We saw great alignment and enthusiasm for collaboration.

You alluded to working with other regulators beyond the FDA. Talk about your engagement with regulators in other regions. Can you share EMA’s vision for international engagement?

You alluded to working with other regulators beyond the FDA. Talk about your engagement with regulators in other regions. Can you share EMA’s vision for international engagement?

Our vision for international engagement is about expanding our collaboration, our communication, and our coordination. No matter how well-resourced, no agency can do it alone; the one message you will get from any agency, big or small, is that they do not have enough resources. Our vision is to see how, within our respective frameworks, we can make the best use of our collective resources, working across borders and among regulators.

We try to have a very open approach to working with our international regulatory partners. When we look at products, about 70% of all the products we deal with have touchpoints with international regulators, whether it is during product development, scientific advice, or life-cycle management, GMP inspections, or pharmacovigilance. We have a wide program of bilateral engagements, but also multilateral. I would mention here the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use, VICH for veterinary drugs, and PIC/S, the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme.

Then, there is the coalition that I am privileged to chair, the International Coalition of Medicines Regulatory Authorities. My ambition as chair is to ensure that we take a strategic international approach and that our activities in different international fora are complementary and not duplicative. In some areas, say if we are working on innovation, we are going to work more on a bilateral basis. But if we are working on postapproval changes, or safety-related issues, this is something that everybody is dealing with, and it makes sense to take these projects forward multilaterally.

If every country deals with a change separately, you can end up with a situation where you are not able to implement the change until the 40th country has looked at it. We are running several pilots on postapproval changes where we are trying to involve additional international regulators in the assessment process, and we are already seeing tangible benefits.

I always say that if ICMRA had not existed prior to COVID-19, we would have had to create it because it gave us a forum — at the leadership level — to influence how things were done on a day-to-day, and practical, level. And what you see is that if regulators like the FDA and the EMA have a similar approach, it will be followed by other regulators. The leadership and influence that we can have together has really helped in shaping some of the wider international convergence that we have seen, particularly during the pandemic.

We assume EMA does a lot of work with WHO and the soon to be established African Medicines Agency. Can you talk about that?

Yes indeed. So, while WHO is not a regulator, it is a body with whom we have a confidentiality arrangement and a very close relationship. The approach is, out of necessity, slightly different to how we approach our bilateral activities because the WHO is already a multilateral agency. We do work in several of its expert groups, including crisis preparedness and ensuring that the low- and middle-income countries WHO typically support can use EMA’s scientific opinions and reviews.

This forms the basis of our collaboration with the African Medicines Agency (AMA), which is being set up to facilitate patient access to effective, safe, and high-quality medicines throughout Africa. We see the EU’s continental networking model as a model for the AMA to emulate. We have a grant from the European Commission to support the AMA. As I mentioned, we have developed our own procedures and systems to support the formation of this agency using the model of reliance and recognition of the work done by national authorities.

We believe that, with our support, we can help to create an enabling environment for the pharmaceutical industry in Africa, but more importantly that we can contribute to the strengthening of regulatory systems on the African continent. EMA is well placed to give guidance on how that might work in a more modern world given that our experience of collaboration goes back to 1995, and of course there has been much progress since then, which we can share.

Some of the projects we are supporting are on regulatory systems strengthening, on joint assessments and joint inspections. The work that we have done with organizations such as WHO and other regulators is forming the foundation of some of the procedures that we are putting in place to support the AMA.

To close, we'd like to ask you what more can be done to enhance medical product safety and quality globally and achieve supply chain resiliency and diversification? And are there ways we can work together to address these?

There are many ways for us to work together to address supply chain resilience and diversification and working together is always better than going it alone, especially for organizations like EMA and FDA. I strongly believe that we have a special responsibility to influence the direction of travel globally because of our collective expertise and experience.

Supply chains have become increasingly complex, and we must look beyond our direct responsibility to how we can address challenges in the quality and availability of medicines from outsourcing, offshoring, and a complex distribution environment. How can we work together to drive for single quality standard for medicines manufacturing across the world? We must take the opportunity to advance technical discussions with global regulators and with industry associations, especially in countries where a lot of the manufacturing takes place, such as India.

We can also use our existing fora to look together at the challenges that we face, particularly shortages, which arise from supply chain difficulties. As for the potential for diversification, we currently look at the needs on a product-by-product basis from a European perspective, but I do think we have more opportunities to look more strategically, and in collaboration, with other countries.

I should mention the recently established Critical Medicines Alliance, where one of the working groups being set up will have a strong international dimension and in which we will be actively involved. If you look at what more we can do to enhance medical product safety and quality globally, we can also support the transformation to more advanced manufacturing techniques. We can ensure that we exchange information on how we regulate emerging technologies and advanced manufacturing approaches so that we see faster uptake of these technologies by medicines developers.

Let me point to some of the cooperation and progress that is occurring between various groups, supported by EMA and the FDA. We have the FDA Emerging Technology Program, the FDA CBER Advanced Technologies team, and the EMA Quality Innovation Group. Collaboration across entities such as these helps us to exchange information and ensure that we have greater knowledge sharing and that if we are developing guidance, we either do it together or ensure that it is aligned.

In terms of quality, we have launched two important pilots under the auspices of ICMRA through its Product Quality and Knowledge Management System Group. One is looking at how we can collaborate both on postapproval changes (as I mentioned already) and the second one is about collaboration on inspections of manufacturing facilities. We are already seeing some positive feedback from industry and other regulators in terms of results and timings. These are good examples of how our cooperation and frameworks help us to tackle some of the tough challenges that we face in medicines regulation. But we also have the opportunity to expand our horizons together so that we can bring a real benefit to the health of the people we serve in our respective organizations.