How do we keep medicines safe and working properly?

In this explainer episode, Rachel Brucoli, Deputy Director at the Medicines and Healthcare products Regulatory Agency, explains how we make sure that medicines stay safe and work properly. 

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

Read more about the MHRA via their website.

You can download the transcript or read it below.

Florence: How do we make sure that our medicines stay safe and work properly? My name is Florence Cornish, and today I'm joined by Rachel Brucoli, who is a Deputy Director at the Healthcare products Regulatory Agency, also known as the MHRA.

And Rachel is here to tell us much more about the topic Well, firstly, Rachel, thank you so much for joining us today. It's great to have you on.

Rachel: Thank you. Nice to be here.

Florence: The first question I wanted to ask you is quite a big question and I guess the crux of this entire episode really. Um, but how do we ensure that medicines are safe and work properly before they get to patients?

Rachel: Yeah, it's an important question, isn't it? So in the UK, medicines are regulated by the Medicines and Healthcare Products Regulatory Agency or MHRA for short. And that's to ensure they, they are safe, they work correctly in a specified disease, and they're made to a high standard before they reach the public. In line with the relevant law, which is the Human Medicines Regulation, before a medicine is allowed to be placed on the market in the UK, the MHRA reviews safety information from clinical trials to ensure that the medicine does not cause unexpected or unacceptable effects.

We also review efficacy data from clinical trials to make sure that the medicine works in the disease or condition and in the patient population that the manufacturer claims it does. Um, another important aspect that's reviewed is how the medicine's manufactured. It's very important that the medicine is made consistently and that every batch meets agreed specifications.

Florence: And so you used that word regulation a few times. When we say that medicines are regulated, how do we do that? What does that process actually look like?

Rachel: Yeah. So different countries have different laws that govern how medicines are regulated. And as I mentioned before, in the UK, the relevant legislation is the Human Medicines Regulations.

In addition, different countries have different pathways or procedures for licensing of medicines, but it's worth noting that the types of data looked at by regulators is similar, and we've got harmonised standards in, in many respects. In the UK, different types of application can be submitted depending on the type of medicine under review.

So for example, the data submitted for a brand-new medicine containing a new active substance that hasn't been approved in the UK would differ from that submitted for a generic medicine.

The licensing process is triggered when a marketing authorisation application is submitted to the MHRA by a pharmaceutical company or a biotech company. And for new medicines, this application contains a significant amount of data that's been generated over, um, a large number of years.

Florence: Mm-hmm. Can you tell us a little bit more about that? What types of information are submitted to you in this process?

Rachel: Yes. So there's three main types of information that, that we receive.

Um, the first is quality data, and that provides evidence that the medicinal product can be made safely, reliably, and to a high standard. It describes what the medicine's made of, how it's made, and provides evidence that the medicine can be produced consistently.

The second body of data contains the results of the non-clinical studies, and there they characterize the pharmacology, and the safety profiles of the active ingredient of the medicine.

And the third section of the application is the results and analyses of all the clinical studies conducted with the proposed medicine. These clinical studies will have been conducted in phases, and they're designed to determine the optimal dose of the medicine needed to treat the specific disease and to provide evidence that the medicine works, or as we would say, is efficacious, and that's usually compared to placebo.

So, what's being measured in clinical studies are clinical endpoints, and they are specific outcomes or events that are measured to determine if a new treatment works.

So, I guess giving an example of that is a cancer medicine, um, where a relevant endpoint that could be measured might include overall, an increase in overall survival or a reduction in tumour size. Additionally, some other important, outcomes could be patient-reported, such as effects on quality of life. So these clinical data will be analysed using appropriate statistical methods, and then this analysis will be presented to the MHRA as evidence to show that the medicine works or is efficacious.

Another important aspect is the data from clinical studies in respect of safety, so they're also used to determine the safety profile. Standard clinical development programs can involve at least a thousand patients, so a reasonable amount of data can be collected on common and less common side effects.

In terms of what kind of happens when we receive the application, different assessors of different disciplines, so for example, doctors, pharmacists, toxicologists, scientists, chemists, review the data received. We check the accuracy of what is being given to us by the, the applicant, and we take a decision on the overall approvability of the medicine.

What is really important to note is that a medicine will only be approved if the MHRA, um, believe the evidence of benefit outweighs any identified risks.

It's also important for people to know where they can get information on the data that's been reviewed by the MHRA. So, if anyone would like to know more about the data that's been considered and the assessment decisions, then they could look on the MHRA website where we routinely publish public assessment reports for all the applications, and that's including those that we refuse. 

Florence: You mentioned clinical trials a couple of times, and I should say for any listeners who might not know that a clinical trial is, is a research study that involves volunteers who are essentially testing out a new medication or a new intervention, and the results from that, as you mentioned, um, will kind of give you information about its safety and, um, any side effects and whether it's working.

I was wondering, are there any other ways that you get information about a medication aside from these trials? Is there anywhere else that you're looking for data as well?

Rachel: So there could be literature data that people submit to us. I mean, primarily for very new, um, drugs, the information comes from clinical studies.

However, you know, once we have approved something, um, we do continue to collect safety data on, on products. So, um, at the time of licensing, we will, yeah, that the main, the main part of the, the clinical data comes from those controlled clinical studies. But in terms of kind of post-marketing, we do encourage patients and healthcare professionals to report any suspected side effects to us through our yellow card system.

In actual fact, companies can continue to carry out kind of further studies, um, after they've got their approval, and that can be to collect more, more safety or even efficacy data.

It's important, I think, to say that once we've given something a licence, that's not where it stops. That we do, and can take regulatory action if, you know, during the life cycle of a product, it emerges that the risks associated with that product start to outweigh the benefit that, that we originally saw.

Florence: Yeah. Um, and obviously, the MHRA play a vital role in deciding whether to grant a licence for a medicine. Um, but is there anyone else as well that has a level of responsibility or plays a role in this process too?

Rachel: Yes. So during that initial licensing phase when we're reviewing that application, we will, um, have the opportunity to ask questions of or even raise objections with, with the, the applicant of the company that submitted that application.

They will have a few opportunities to provide further data or different analyses that might allay our concerns. But a really important, um, group of people that do contribute to our decision-making, um, are our independent experts that we can use to, to get advice.

So we have expert advisory groups and also the Commission on Human Medicines or CHM as, as we would commonly refer to it. And these are very important because many of the experts on CHM, for example, are practicing clinicians, and so they do give us insightful advice because they're the people that are treating the patients on a daily basis.

We also, um, where possible, try and bring in patients and public perspectives into consideration at various stages throughout the kind of regulatory life cycle of a, of a medicinal product.

And so patient public involvement engagement is very important to gain wider perspectives, and it helps us to kind of put patients first, which is really at the heart of what, of what we do.

Florence: And finally, of course, I have to bring us back to genomics because this is a, a Genomics 101 podcast. Are there ways that genomics is playing a role in the way that we develop medicines?

Rachel: Yeah. I mean, genomics plays a vital role in many ways. Um, mapping human genes and identifying DNA mutations that cause disease allows companies to develop targeted treatments and personalised therapies. I mean, one such area that a lot of people may be familiar with is pharmacogenomics, and that's where DNA can be used to understand how an individual's body will break down a medicine and can help set appropriate doses for that particular patient, and therefore reduce any kind of potential unwanted effects.

Genomics can also help diagnose rare genetic conditions or even guide the treatment of specific types of cancer. And a good example of this is breast cancer. Um, so where understanding the activity of specific genes inside the tumour tissue that's taken at biopsy, that can help guide treatment options to give the best outcome for that particular patient.

I mean, moving on into kind of terms of rare diseases, 3 and a half million people live with a rare disease in the UK. That equates to 1/17. Um, lots of stats, but eighty percent of these rare diseases have a genetic cause, unfortunately, though, less than 5% of these have an approved treatment at the moment, and that's largely because there's lots of challenges with developing medicines for rare diseases.

It's just simply not possible to do those kind of large-scale clinical trials that we were talking about earlier. Um, and so it's, it's not easy to get a sufficient amount of evidence of safety or indeed of efficacy. I mean, in some cases, the, the, a genetic disease could actually just affect one person.

So the MHRA does realise this is a pressing need, and it's a growing area at the moment. And so we've developed a rare disease, um, therapies regulatory framework, and that aims to provide a flexible regulatory approach to ensure that efficient development of medicines, addresses this high unmet, clinical need.

It's probably worth noting the pathway is not specific to any particular technologies, but we do anticipate that several gene therapies and individualised medicines will come through this pathway. And so it's a really, really exciting time in this field.

Florence: Yeah. Well, I think we'll finish there. Thank you very much, Rachel, for joining us today. It's been such an interesting conversation.

Rachel: No, thanks for having me.

Florence: If listeners want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts. Thank you for listening.