Dr. June Raine DBE is Chief Executive Officer of the UK’s Medicines and Healthcare products Regulatory Agency, a position she’s held since 2019. She trained in medicine at Oxford after completing a master’s degree in pharmacology. Her interest in drug safety led to a career in medicine regulation that has spanned a number of roles in assessment, management, and strategic development within the U.K. national authority. She was elected in 2012 as the first chair of the European Pharmacovigilance Risk Assessment Committee and is also co-Chair of the WHO Advisory Committee on Safety of Medicinal Products. Her special interests are in monitoring the outcomes of regulatory action, risk communication, and patient involvement in the regulatory process.

Staff from the FDA’s Office of Global Policy and Strategy (OGPS) spoke with Dr. Raine in advance of her meeting in London with a delegation of FDA senior leaders, including FDA Commissioner Dr. Robert M. Califf.

After the FDA meeting, OGPS checked in with Dr. Raine again to get her thoughts about that visit. 

Let’s start out with some background for our readers. What are MHRA’s responsibilities or remit and how do those responsibilities compare to those of the FDA?

The Medicines and Healthcare products Regulatory Agency or, as we call it, MHRA, is the UK's regulator of medicines, medical devices, and blood components for transfusion. And we're clearly responsible, like all health care product regulators, for making sure that these products meet the expected standards of safety, quality, and efficacy. We play an important role in bringing innovation to patients without unnecessary delay. We're also the UK’s National Control Laboratory responsible for carrying out independent batch release testing of biological medicines. And as a World Health Organization (WHO) Collaborating Centre for Biological Standards we produce over 90% of the WHO’s international standards which set the quality of biological medicines globally. So, we're quite an unusual regulator in that we have laboratories as well as the regulatory review functions and inspections. We also have access to an important and very valuable source of real-world data from UK general practice, through our Clinical Practice Research Datalink.

However, the main difference between MHRA and the FDA is actually the scope of the products we regulate. In the UK we have a separate regulator for food, for veterinary medicines, and for consumer products such as cosmetics, and we don't regulate tobacco, though we do have a role in registering nicotine e-cigarettes. In terms of our reputation, if I had one wish, it would be that the MHRA was as well known as the FDA. I often find myself saying we're like the FDA – people always know what that means!

The fourth anniversary of the UK’s departure from the EU took place recently, on January 31. So, in light of the UK’s departure from the EU, what has been MHRA’s vision for the future?

Certainly, if I talk about my immediate reflections, our departure from the EU network of regulators has brought home the vital importance of working in partnership with other regulators internationally as well as with our health care partners nationally. The EU exit has also given us new opportunities to consider how we bring medicines and medical devices to the UK market. But what remains unchanged is our commitment to keeping patients safe and enabling access to the high-quality, safe, and effective products that people expect. Central to our vision is to be an enabling regulator, not a watchdog.

We have a corporate plan, one that guides our pathway from 2023 to 2026. We're just completing the first year and we have four very clear pillars - or objectives - to our plan. The first is to maintain public trust. I think without that we can't regulate effectively, and that public trust depends on transparency, being proactive, being accessible so that our independent decisions are not hidden away and we are able to articulate how we achieve that balance between benefit and risk for all medicines.

The second pillar is enabling access. We want to be a very responsive, reliable regulator so industry can plan when they want to develop and introduce a product and deploy it in our National Health Service. We're improving our pathways to take time out of the regulatory process. The example that's front of mind since January 1 is our new International Recognition Procedure with trusted regulators, including the FDA. We’re working hard to enhance our offer of regulatory pathways to ensure that U.K. patients can benefit from new medical products at the earliest opportunity.

The third pillar is regulatory and scientific excellence, particularly with strategic partnerships. In the UK, we are privileged to partner with Genomics England on the impressive work that they're doing to unlock how the knowledge of pharmacogenomics can benefit regulation. And we're watching Our Future Health, which is a major program following the health journey of 5 million people, so that we can start to consider the genetic basis of those health journeys. So, there's a way to make alliances work so that regulation improves.

I can't finish without talking about our fourth pillar, which is being an agency where our people flourish and where they build great careers. A member of staff at the MHRA once said to me, “This is where I'm spending the best part of my career.” We want to see that feeling echoed across our staff community, as well as being a responsive, service-orientated regulator. Overall, our Corporate Plan with four pillars sets out a big ambition, but it is also focused on the here and now.

You just mentioned enabling access as one of your pillars. In talking about that you mentioned new procedures with other regions for the recognition of approvals and new pathways to support innovative product development. Could you elaborate more about this? How do you see these being utilized and if, or how, they may shape the regulatory landscape in the UK?

It's a really important question, and it has been an evolving picture, given that since 2020 we have been a member of the Access Consortium with Australia, Canada, Singapore, and Switzerland. It's a model of work sharing rather than recognition or reliance. A dossier can be allocated to different regulators for the very special contribution they're able to make in preclinical, quality or clinical data. A nice example would be the five-way assessment in 2022 of a medicine for vision loss related to diabetes, which was able to take months out of the procedure time. And I want to pay tribute to Project Orbis, which has done extraordinary things to get cancer medicines to those who really cannot wait. We've had 10 approvals for new cancer medicines and eight approvals for extension of indications for existing oncology products between May 2021 and December 2023. It is proving its exceptional worth in clinical situations where time really does matter.

That's the scene setting. Where are we now? We've launched our International Recognition Procedure with seven reference regulators, and it's beginning to grow as of the beginning of January this year. There are two pathways: one is a straightforward, 60-day pathway with regulators where there are few differences between our standards and theirs, and a second where the applicant may have made some changes to the original dossier, which takes longer, at 110 days. So, watch this space.

This work goes back to the U.S. National Academies’ 2018 Report ‘Regulating Medicines in a Globalized World’ about the need for increased reliance among regulators. In fact, I remember once giving a talk to a nonregulatory audience, and the question put to me was “Why do we need more than one regulator?” I would always say that benefit-risk of a product is judged in a particular health care context, but if you have the same evidence on benefits and harms, why not come together to use expertise and resources efficiently and make regulation work optimally for our patients and health care systems globally? Our new International Recognition Procedure will be a very important tool in our regulatory toolbox.

What your question really goes to is how will international recognition impact on our regulatory role for the future? My hope is that we will certainly retain some of the important innovation pathways where we add value. Let me give you an example in relation to personalized immunotherapies. Because the U.K.’s health ecosystem is joined up, we're able to bring clinicians and health care organization leaders into the regulatory discussions. In this way, we can consider dedicated regulatory pathways for products that have a very short shelf life or products that are tailored to the genomics of a particular cancer or indeed therapies for very rare genetic disorders. These are quite a challenge for regulation, and it's not going to be ‘one size fits all.’ The question is whether we can license platforms as opposed to products. This is a really exciting time in the evolution of regulation, and my ambition is for our voice to be part of that international discussion that is now ongoing.

You’ve been in leadership roles at MHRA for a quite a while and CEO since 2019. With your experience, what do you see as the biggest challenges and biggest opportunities we have as regulators?

This is a really important question, and I'm honored that you’ve given me the privilege of reflecting on this. First of all, I believe that being part of patients’ lives, and involving patients and the public in our decisions, is an important journey we’ve embarked on as regulators. It’s important that patients and the public can have a meaningful involvement in the work of regulators, and it’s also important that regulators start to align on what we are capable of delivering for patients, at a time when public expectations are growing, and rightfully so.

Secondly, we face an important challenge with the risk-proportionate regulation of rapidly evolving innovative technology, such as artificial intelligence and software as a medical device. For these products, there is a scientific and regulatory challenge to get the balance right between protecting the public from risk whilst not delaying access to potentially enormous benefits for patients and health care.

Thirdly, as a pharmacovigilance and safety-focused regulator, I always want the best evidence on which to base decisions and in a timely way — the ability to link large datasets and integrate data to inform our decisions is with us now. I would really like to see this as a challenge we'll conquer, perhaps not quite in my professional lifetime, but very soon after it. It could be transformative. And better decisions that are timely have got to be the goal of every regulator. Three big challenges, all of which will prove to be opportunities if we get regulation right!

This tension between balancing the need for supporting innovation and maintaining evidentiary standards for safety, efficacy, and quality is certainly a tightrope all regulators have been following for a while. What have you learned over the years about that? Do you have any thoughts about how best to approach this challenge?

First of all, learning from one another is key, and this is why international partnerships in regulation, which we talked about earlier, are crucial. In the U.K. we have followed with great interest the FDA’s Breakthrough Therapy designation and the European Medicines Agency’s Priority Medicines (PRIME) initiative, which offers early and proactive support to priority medicine developers to optimize generation of robust data on and risks where that tightrope is walked between understanding promise and ensuring that we have adequate data in a timely way. A safety net of vigilance around those decisions has got to be as strong as it can possibly be.

The experience on breakthrough therapy, PRIME, and our own Innovative Licensing and Access Pathway (or ILAP as it's called) or the Promise pathway coming through the Access Consortium – all these initiatives build our ability to get data collection in place and in parallel to take the public on that journey of how to look ahead at and understand how uncertainties around the benefit-risk decision may be reduced.

Secondly, I would highlight the special challenge of medicines and vaccines for use in healthy people. We know that for people with a serious diagnosis such as an oncological condition or an inflammatory bowel disease, risks will be taken. With serious neurological conditions such as multiple sclerosis, patients will accept risks even when their health professional doesn’t agree.

But when a healthy person is faced with a choice, and we're going to see this increasingly, that’s a different challenge. I already mentioned Our Future Health, which will be following people through their health pathway and collecting genomic data. A particularly important study is the ‘Generation Study’ by Genomics England, which is currently under way to sequence the genomes of 100,000 newborns to look for a specific set of rare genetic conditions that affect babies and can be acted on. If you know from the genetic risk profile of a baby, there’s a relevant product but the regulatory regime has authorized that product on the basis of a clinical trial data set, say from the age of five (if we're lucky), do you say to parents “your child will need to wait until he or she is five to access this product?”

I believe we're going to be changing the regulatory paradigm when it comes to health and prevention, perhaps to what can be called ‘preemptive’ health. I think that will be a huge challenge for us all, and I hope that international regulators can put in place now the building blocks to help pave the way.

What a wealth of data you will have. Will it help in the collection of data for underserved populations?

All of us are looking in the eye of those in underserved populations and finding we should be doing a lot more. There are certainly data sources that can be better used, and I’m pleased to say that our own Clinical Practice Research Datalink now has a number of tools to correct bias in this regard. There is a huge opportunity to harness artificial intelligence and modeling to support underserved populations.

I pay tribute to the incredible collaboration we've had with the FDA’s Division of Pediatrics and Maternal Health, and to Dr. Lynne Yao and colleagues who've really forged ahead with getting labeling requirements in place to improve the safe use of medicines in pregnancy and lactation. It's a magnificent piece of work and every pregnant individual should know about this. The outcome of the time collaborating with the FDA with the EMA is measurable in healthier mums, having healthier babies and that's something to be truly proud of.

To demonstrate this, when we recently looked back at our dataset of about 4,600 clinical trials, my colleague who undertook this review said, “I'm really sorry, there are only 52 trials in pregnant women.” My reply was, “Don't apologize, that’s 52 more trials than there might have been but for the FDA, the European Medicines Agency (EMA) and the MHRA collaborating.”

The FDA and MHRA have a long history of collaboration and you've mentioned some. Could you share your views on some of what you consider the most notable collaborations?

One collaboration that's front of mind at present and for all good reasons is the particularly strong relationship that our MHRA Software and AI group has with FDA colleagues in the Digital Health Center of Excellence. At a time when our government and health leaders want to take advantage of this amazing opportunity, but want to do so safely, this could not be more opportune. Collaboration that helps to promptly create the right conditions for advances in technology to be used safely is vital.

I learned a big lesson from researchers and developers in the past who told me that when regulators don't set any guide rails, they were inhibited from moving forward. The Good Machine Learning Practice Guiding Principles-- jointly produced together with Health Canada – which were recently further updated, have actually distilled a shared approach to managing AI [artificial intelligence] adaptivity. I understand there are two more publications under development, one on transparency and one on identifying and managing bias. We want to continue this work, by considering post market surveillance for AI and the life cycle concept for AI.

All credit goes to the colleagues who are getting their heads round how we can channel these exciting opportunities for the public health. It's an exemplar of how collaboration should work. We in the UK have to introduce new legislation, and the MHRA has published a roadmap for our med tech regulatory reforms. We must give that signal that we’re getting the balance right, not being too restrictive, and enabling progress. For example, we're preparing to launch an ‘AI Airlock,’ a new type of regulatory sandbox, which will see advanced AI technology used in health service settings with strict safety controls. This regulator-monitored area will allow developers to generate robust data for their advanced technologies, ahead of navigating regulatory approval.

I cannot omit to mention again our collaboration with the FDA’s Project Orbis where we look to what the FDA brings to bear on innovative medicines in terms of oncological expertise, which is world leading. I must also credit the work that the FDA did during the COVID pandemic when we provided updates on all the clinical trials during that very difficult period. The ability to look at which trials would deliver decision-relevant data, helped to focus minds on the timely decisions regulators could make in terms of effective medicines for the public.

You've mentioned the Access program that you have with other regulators. Are there other examples of your global engagement strategy or how you've collaborated with other regions of the world?

The Access Consortium program with Australia, Canada, Singapore, and Switzerland is certainly a significant strategic initiative for us because it's a model of sharing assessment work and creates a market of some 160 million people which is attractive to developers.

In terms of other examples of global engagement, the International Coalition of Medicines Regulatory Authorities (ICMRA), which has come into its own during the COVID pandemic, is an important focus for MHRA. ICMRA is growing in its potential as shown by some recent key developments, including the Pharmaceutical Quality Knowledge Management System (PQKMS) under FDA’s leadership – a name that doesn't run off the tongue, but an initiative which is going to set the standard for how regulators can collaborate internationally, in this case via coordinating variations.

So, ICMRA is now a pillar of international collaboration. The MHRA has been able to contribute significantly to the work of the Vaccines Vigilance Network and the Public Health Emergency Clinical Trials Network and co-led development of a Crisis Management Standard Operating Procedure which was actually written in advance of the pandemic. And then, of course, we have the International Conference on Harmonization and the International Medical Device Regulators Forum, which the FDA chairs.

In the field of pharmacovigilance, for the last four years we have been a partner alongside the FDA of the African Union Smart Safety Surveillance program, or AU-3S. This groundbreaking initiative aims to provide the tools and training for African countries to operate their own safety monitoring systems. During COVID, the AU-3S program was vitally important in enabling countries to detect and manage safety signals as the COVID vaccination programs were rolled out. Around 40,000 reports of suspected adverse reactions were collected though AU-3S during the vaccine deployment, and the initiative is now expanding from the original five countries (Ethiopia, Ghana, Kenya, Nigeria, and South Africa).

You already mentioned the work that has been done for the inclusion of pregnant and breastfeeding individuals in research. What are some other ways that we can more broadly improve diversity inclusion in clinical trials?

At the moment, we are debating this question! Our clinical trials legislation is due to be revised this year, and we have consulted publicly on ways to approach improving diversity so that trials represent the population who will be using the product. One of the hopes I have for our coming discussions is that we'll understand what the impact has been in the U.S.A. of the new FDA instrument introduced to improve inclusivity. We want to get the balance right. I understand that there are trial phases where this is more important, but the ultimate question is when someone from an underrepresented group, whether it's a pregnant person, or someone from an ethnic minority group, is offered a medicine or vaccine, they will ask, “Has this been tested on someone like me?” We have to be able to answer that question.

We've had a particular interest in representativeness of populations in medical device studies. Major questions were raised during the COVID pandemic regarding the accuracy of measuring oxygen levels using pulse oximeters in people with darker skin tones. We're shortly anticipating an important report that will help to spotlight what we could do better. So, diversity is not only important for pharmaceuticals – it’s very relevant for med tech and medical devices too.

Turning back to pregnancy and lactation where our regulatory decisions affect safe access by an underserved population, there have been lessons which are relevant to other underserved populations. I recall an instance when use of the antiretroviral darunavir in Africa was associated with reports of ineffectiveness in the third trimester. The regulatory response at that time was to advise against use in pregnancy, when, in actual fact, the response could have been to adjust the dose. Now we're in the fortunate position of being able to do mathematical pharmacokinetic, pharmacodynamic modeling, and we can predict the right dose. And our Clinical Practice Research Datalink now has functionalities that enable researchers to address health inequalities, including data on ethnicity and socioeconomic status.

In your opinion, what more can be done to enhance medical product safety and quality globally? Are there ways we can work together to do so?

International collaboration to improve medical product safety and quality globally is growing, albeit perhaps on a slower trajectory than we would like. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) is doing vital work. And the ability for ICMRA to convene and to progress initiatives like the PQKMS is important, to make sure that we can rapidly respond to emerging global safety issues such as the case of contaminated cough mixtures harming children. Internationally regulators are sharing information and making prompt decisions.

The work that the FDA rapidly undertook on the issue of heparin contamination some years ago was exemplary: we all had access to data, we exchanged risk assessments, and the whole international community was able to respond. I should also mention the Good Manufacturing Practice inspections, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) and the collaborative work it does. It’s also worth mentioning that managing medicines supply shortages is a broader issue than regulators alone can deliver. Effective handling includes our working with health departments and other health care organizations. There is still a way to go, when it comes to anticipating supply disruption, particularly in areas of access to generic medicine and sterile product.  Overall, we need an international, collaborative response that proactively tackles root causes. It's only through working together that we’ll make progress.

In the area of supply diversion and counterfeit, sadly our penalties often don’t seem to match the crime. In Africa, it’s estimated that 50% of antimalarials are falsified. Joint law enforcement efforts such as Operation Pangea, the WHO-led international initiative that targets the illegal internet trade in medical products, and our work with the WHO’s Member Statement Mechanism, do allow us to raise our game. Just this week the MHRA published that in 2023 we seized illegally traded medicines with a street value of £30 million ($38 million), which included more than 2 million doses seized during Operation Pangea.

All the time, regulators are trying to educate potential perpetrators against criminal activity, where possible, with severe penalties and by closing down websites. But let's not delude ourselves. When a website is closed down, another one springs up. So, let's work together internationally to constantly educate the public about the risks of buying off the Internet – whether it’s a medicine or a medical device. We see the emerging issues with weight loss medicines, the Glucagon-like peptide-1 agonists (GLP-Agonists). People sometimes, in their wish to help themselves, make unwise decisions to access medicines via the Internet. Let's keep that constant message that your health care provider will provide the best advice for you and it’s not worth taking risks.

Quality is the starting point. The public expects and deserves medical products of appropriate quality. As regulators become more sophisticated in our benefit-risk judgements, we also need to return to that first principle, that a medicine should be what it says it is. It should be manufactured consistently, batch to batch, and should fulfill the finished product specification throughout the shelf life. The international collaboration of medicines inspectors who keep bringing this to the fore is vitally important, for public confidence. There's nothing quite the same as the inspectors seeing and believing and being able to assure the public that when they have their vaccination or take their medicine, that we really have checked it out.

And that sort of brings us back to, one of your pillars, which was trust. And so, I wanted to close by talking about one of the FDA’s priorities – combating the plague of misinformation and disinformation, which can indeed erode trust in our institutions and lead to serious public health consequences for society, such as outbreaks of vaccine preventable illness. Could you share your thoughts on how we can work together in the fight against misinformation and disinformation?

I would like to respond by focusing first and foremost on the transparency of what we do and the proactive communication of the data on which our decisions are made. It would be unrealistic to make this sound easy and the present-day challenges with social media and other sources of information make our job in this regard very, very difficult. But I do think that by adopting the principles of openness and transparency we help the public see and understand what we do. The public expect us to be open about our data and be able to explain how we handle adverse drug reactions and adverse events for devices. As regulators, we can learn from one another on what works well.

There is a special expertise in how to communicate in a balanced way, treating the public as the discerning consumers that they are and treating every question as a valid one. There is nothing that should be dismissed, and if there's some worry in someone’s mind, it's valid. In particular, in the area of vaccines, and I know Commissioner Califf has taken a special interest there, we need to be very cognizant that there will be hesitation as well as refusal. It's those who are hesitant, particularly parents, who deserve the time and the explanation with materials and information that supports that decision that a vaccine is safe. I think if we can show that kind of respect for people's questions, then we will have gone quite a long way.

Let's go on that journey of public engagement to make data accessible and understandable. There are people who are extremely skilled in this, and I've been fortunate to work with some. Trust is embedded, I think, in transparency and openness, but also in people and the devotion and commitment to public health that you need to stand for and show that you stand for. We need to demonstrate the ability to listen and to change our minds, if necessary. We need to have a partnership with patients and the public in this regard. We're here for them. And in a sense, our duty is to make sure that patients and the public have that confidence and trust in us. It's not an easy journey though, and I will readily own up to that.

You just met with an FDA delegation led by Commissioner Califf. Could you reflect on that meeting?

I had three key objectives going into our series of meetings with the FDA delegation led by Commissioner Califf: to further cement our already positive relationship, to identify priority themes or areas of focus in regulation, and to agree how we will together take forward work to address these. I am delighted to say that the Commissioner and delegation from the FDA shared my commitment to achieving those objectives.

Together we found a number of important opportunities for further collaboration, including first of all sharing perspectives on combatting misinformation/disinformation and the harm this can cause. We agreed on the importance of strengthening supply chain resilience, while championing a ‘one quality manufacturing standard’ culture in our network of international partners. We endorsed the importance of aligning on innovation in clinical trial practices and enhancing the diversity of clinical trial populations, while reflecting on the need to drive forward work on medicines for use in pregnancy and lactation. 

We committed fully to the goals of addressing health data governance internationally and grasping the opportunities of use of real-world data to enhance regulatory decision-making, including evidence generation in areas where there are data ‘deserts’. Finally, we looked ahead to continuing to build on our productive collaboration in relation to software and AI, and supporting increased international reliance to improve access to medical devices.  

As our meeting drew to a close at the Royal Society, we reflected under the watchful gaze of Benjamin Franklin, Fellow of the Society, on his groundbreaking discovery in understanding the nature of lightning. I can confidently say that our productive discussions had flown a kite or two, generated some electricity and reached a consensus that the key to progress is continued collaboration, in the best interests of science, regulation and the patients we serve.

Dr. June Raine DBE is Chief Executive Officer of the UK's Medicines and Healthcare products Regulatory Agency, a position she’s held since 2019.