Q: What is your role at the MHRA?
I’m Shirley Hopper, a medical doctor by training. At the MHRA I manage the teams that look after the licensing of innovative products. Within that there are two different types of medicines: chemical and biological, depending on the type of manufacturing process. My team and I look after both, so our work covers all new medicines.
Q: How would you explain the purpose of your teams?
So the core purpose is to review applications for and grant a licence or marketing authorisation for new medicines where appropriate. That is specifically medicines that have not been used in the UK before – not generic copies of other medicines which are already available.
We want patients to have access to new medicines that are going to be effective and safe and want to be able to do that in the shortest time possible, particularly for medicines and treatments for which there is an urgent need for these patients. That is why we get up in the morning.
Q: What typically goes into the process of a new approval? What are the key considerations?
The developer who has made an application to us has to compile a dossier of data which includes the results of tests they have carried out and other pharmaceutical aspects of their medicine. Key to this is the quality of the medicine and how it will be controlled with each new batch that is produced, and we have scientists and pharmacists who assess this key safety aspect.
In the beginning laboratory and non-clinical testing is carried out by the developer, and when the safety is judged to be at an adequate level, studies begin in humans usually through healthy volunteer studies, also known as early phase studies. Once a safe dose is established, further (and larger) studies are carried out in patients who have the condition the developer is trying to treat, to confirm safety and effectiveness.
From our side, we have multi-disciplinary teams that look at the dossier provided by the developer in parallel. This includes medically qualified clinical assessors, pharmaceutical/quality assessors, non-clinical assessors, statisticians and clinical pharmacologists. We also review the information that will be provided to healthcare professionals and patients to ensure safe use of the medicine in practice. We have a timetable with milestones to help us with the review process. This allows time for the applicant to address any questions that we may have.
Q: Often the key question is the benefits vs the risks of the product in question. In approval terms, how hard can it be to balance the two sides?
The individual who leads on the benefit risk assessment is the medical assessor, and they will want to be assured that the quality of the medicine meets our stringent regulatory standards. No medicine is completely safe, so we will ensure that the benefits are clinically meaningful and outweigh the risks. We work with risk management plan assessors from our Safety & Surveillance team to ensure that the safety profile is carefully monitored after approval, and any risks can be managed in practice.
Where appropriate, the MHRA aims to involve patients at every step of the regulatory process to ensure that the balance of risk and benefit is considered from all perspectives.
Q: There is an assumption that the MHRA and the MHRA alone makes a decision on an approval, but the Committee on Human Medicines has a big role to play as well. Can you talk through how this process works?
Yes, we consult the independent Commission on Human Medicines (CHM) on innovative medicines applications that come in via our national route. The CHM includes a wide range of well-regarded experts who can advise us on the safety, quality and effectiveness of medicines.
Q: To build on that point, patients and more generally the wider public are waiting on our approvals for innovative medicines, but that approval doesn’t necessarily mean the product is instantly available on the market. Can you talk about the work we do with other organisations such as the NHS and NICE?
Yes. Manufacturers will typically make early applications to Health Technology Assessment (HTA) bodies – for example the National Institute for Health and Care Excellence (NICE) in England – so they will be submitting information to the MHRA and these bodies in parallel. This is because NICE also need to make their own appraisals and subsequent recommendations, which are also based on a review of clinical and economic evidence (how well the medicine or treatment works in relation to how much it costs the NHS). The NHS is then legally obliged to fund and resource medicines and treatments recommended by NICE’s technology appraisals.
A manufacturer making early applications to HTA bodies alongside the MHRA can help to speed the process up. Alongside that, with the consent of the manufacturer concerned we may share certain information with HTA and NHS bodies across the UK to help facilitate their parallel assessment of the medicine.
Our Innovative Licensing and Access Pathway (ILAP), for which NICE is a partner, provides a single integrated platform for sustained collaborative working, allowing for enhanced coordination and monitoring of important product development activities.
Q: By definition your team facilitates innovation – what approvals have your team been a part of in recent years that stand out?
Casgevy, a new treatment for sickle-cell disease and transfusion-dependent β-thalassemia, which we approved in November 2023, is a really good example of the work we have done.
Casgevy was the first medicine to be licensed that uses the gene-editing tool CRISPR (its inventors won the Nobel Prize in 2020). We were the first in the world to approve this as we recognised that it was a really transformative product for patients with very difficult to treat conditions.
The product is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long.
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Welcome to the March issue of the Med Tech Regulatory Reform blog series. As the leader of a team which includes many talented female scientists, I am particularly delighted to be publishing this at the start of British Science week and on International Women’s Day.
It has been a busy month: we announced, alongside our delivery partners, the eight products moving into the Innovative Devices Access Pathway pilot; the statutory instrument Medical Devices (In Vitro Diagnostic Devices etc.) (Amendment) Regulations 2024 (IVDR for NI for short) completed its journey through parliamentary debates and will come into force on 21 March, and in line with our published Roadmap, we were delighted to be joined by 1400 people on our first webinar this week to discuss the scope, classification and essential requirements of the future new core regulations.
At the webinar my colleagues gave some detail about our intentions to clarify the regulatory status of products specifically intended for the cleaning, disinfection or sterilisation of devices; for prediction or prognosis of disease; which support conception; are used for investigation, replacement or modification of a pathological process and which provide information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations. We talked about how we will provide clarity for device users on how, and when a device can be used according to its intended purpose to reduce risks to patients associated with potential misuse and gave an update on the intended new definition of Software as a Medical Device.
We gave an update on the proposed changes to GB classifications for general medical devices and IVDs, which are risk-proportionate, more closely aligned to international systems and provide additional clarity for device manufacturers. We had some great questions which we will use to help develop useful guidance to support these new proposed regulations. We will publish a recording of Tuesday’s webinar on our Med Tech regulations web page - anyone who is interested can register online to receive updates to this page.
Webinars are a great way to reach wide audiences, and where we can, we will continue to use that format to communicate our draft new policies, but for many areas, we will need smaller sessions run under the Trusted Advisor Principles I told you about last month. In order to ensure that we can maximise the value of those sessions, in the last month we have adjusted our Trusted Advisor Principles, to enable those attending to share what they learn more widely and consult appropriate experts within their organisations in order to feed back.
We have several stakeholder discussions under Trusted Advisor Principles in the coming weeks including one to examine the detail of the regulations concerning Approved Bodies and two to discuss our plans to exempt certain devices made in Healthcare Institutions from some aspects of the regulations. In addition, we have had requests for discussions on some additional issues linked to the regulations, such as system capacity and performance. This will be held 18 March. Members of Trusted Advisor Groups are sourced through the relevant Trade Associations.
We know that for companies operating globally, the Framework for International Recognition is going to be a vital part of the new regulations. We continue to gather feedback from the day long Trusted Advisor Group event on International Recognition on 26 January and in parallel, work across government and the health system to ensure that others who may be impacted are involved in the process. To give more certainty, we aim to publish an outline of the International Recognition Framework for medical devices later this Spring aligned to the Life Sciences Council, subject to necessary approvals. Ahead of that we will be testing our framework by walking through it with some exemplar products to iron out key issues. These products will not be granted approvals through this process rather this will be an opportunity to test the current policy thinking in practice.
Next week is the 25th Session of the International Medical Device Regulators Forum (IMDRF), hosted by the US Food and Drug Administration (FDA), in Washington DC. The meeting runs from 11-15 March and includes public sessions as well as closed sessions for the IMDRF management committee only. I am excited that on one of the public days the sessions will all focus on International Recognition. I will be heading to Washington at the weekend with some of the team and the MHRA will be co-chairing one of the panels. This will be a huge opportunity for us to add to our learning not only on what has worked well in other jurisdictions but also to understand what others plan to do in the future around this critical issue. It is also a reminder of how important our regulations will be beyond the framework for International Recognition. Whether other regulators will, at some point in the future, be minded to recognise the UKCA mark is beyond my control but I do know, if that call comes, we need to be in a position where we can say the UK regulatory framework is as good as it can be, and one that other regulators should feel confident to rely on.
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It’s International Women’s Day and Mandy Budwal-Jagait, Head of our Good Clinical Practice (GCP), team discusses why it’s important for us to Inspire Inclusion in the workplace.
Trust, representation, opportunity, understanding, belonging. These are just a few of the many words that come to mind when I think about what diversity and inclusion mean to me. Today is International Women’s Day, which aims to ‘Inspire Inclusion’ for women in all aspects of life. But I believe this sentiment should be carried beyond today and beyond gender alone.
We’re all individuals with our own unique differences, be that race, gender, sexual orientation, religious beliefs, socio-economic background, physical and cognitive ability. However, there’s a richness in creating a diverse and inclusive environment that nurtures a sense of belonging and understanding to get the best out of every individual for themselves and for society.
When individuals feel the security, safety and trust in the environment they’re working in, they can bring their whole selves to work. This can inspire confidence in putting their ideas or points across, knowing they’ll be heard, valued and have an equal voice.
Having diverse perspectives helps generate new ideas, awareness of bias or areas requiring further review, helping us develop effective solutions. It helps allow the bigger picture thinking which is vital in the work that we do to serve the public and society at the MHRA. We must support and inspire the journeys of people from diverse backgrounds so we can continue to create a rich environment in our industry.
When I think back to my own journey, my drive started at the age of 8 or 9. I’d just lost my grandfather and I wanted to find the cure for cancer. I thought the only route was to become a doctor as culturally that was a respected and stable job. However, I soon realised that it wasn’t the medicine, but the science that excited me the most, and this took me to an MSc in Toxicology, where I was inspired by the drug development process.
When I finished university, I knew I wanted to work as a Clinical Research Associate (CRA) in the pharmaceutical industry, but this is where I met my first hurdle, I had no idea how to go about it. I had no role models in industry, I didn’t know anyone who could help, so I did my own research into the qualifications needed and self-funded my ICH-GCP course.
I then encountered a few recruiters who gaslighted me and made me feel that I stood no chance in getting a role out of university as a CRA. But I knew this was what I wanted, and thankfully, one great recruiter contacted me about an entry level CRA role where a candidate had dropped out last minute and I got the job!
Culturally, being in a role as a single or married woman who spent a lot of time travelling and staying away was not seen as ideal at the time. I’m thankful for a supportive family who recognised my drive to make a difference and always supported and encouraged me.
So here I am, Head of GCP at the MHRA, playing my small part in a much greater ecosystem! I’ve kept the drive I had as a child, it’s this drive that makes me stay in this industry, as any one of us and our loved ones can become ill, and we’ll all need medicine in our life. I want to make sure that there are safe, effective treatments available for all.
That’s an important part of our work as a GCP team. We inspect clinical trials to make sure the participants are safe, and that the data generated are reliable. We’re also involved in policy and guidance development and have a key role in maintaining public trust in taking medicine.
Just as diversity and inclusion are needed in the workplace and society, it’s vital for our clinical trials if we’re going to inspire trust in the populations who are going to take these medicines. We’ve seen changes in trial design and recruitment practices to reach underserved populations, but there’s still work to do to build that trust.
As a diverse GCP team, we bring different perspectives, insights and experiences to the table, which are valued and respected and we all champion each other to succeed. I’m proud that colleagues in the MHRA have a shared commitment to a common goal of protecting public health and demonstrate this commitment on a daily basis.
Like many other organisations, I believe we’re on a journey to becoming a more diverse and inclusive workplace. Whilst there’s work to do, I’m proud of the support offered by the Compliance Teams who continually work to define and improve our culture as teams of inspectors.
Blogs and articles from colleagues on Black History Month, LGBT+ History Month and Ramadan guidance is a great initiative which we can continue to build upon for other groups and communities. I personally found the support from Civil Service networks such as The Ethnic Minorities Women Forum and previous Race to the Top Networks invaluable.
If we’re going to continue to inspire inclusion in the workplace we have to build on the initiatives in place, but most importantly demonstrate our intention for impactful change.
I recently participated in the Race in STEM Roundtable where we discussed the need to ensure that our efforts result in change. To support this, education is important and being open to learning as well as being aware of our own unconscious biases. We also discussed the importance of role models and if you can see it, you can be it, which was certainly true in my case when I joined as an inspector. Finally, we have some work to do in having sponsors in the workplace who can champion individuals within their career within the agency and provide guidance and support.
I hope that continuing to have these discussions and shining a light on the importance and benefits of diversity and inclusion will continue to inspire people of all genders, races and backgrounds in the future, and help them see the way towards their goals as I did.
]]>On 9 January 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) published its Roadmap for the delivery of the future regulatory framework for medical devices. In the first of a new blog series, Laura Squire, Med Tech Regulatory Reform Lead and Chief Officer Healthcare, Quality and Access, shares an update on the MHRA’s progress towards implementing the regulatory changes set out in the Roadmap.
It’s a privilege to lead the MHRA work on reforming our regulatory framework for medical devices, taking advantage of the opportunities presented to us as a sovereign regulator.
The aim of this work is to create a framework which is responsive to the needs of new technologies, strengthens patient safety and provides the certainty and clarity that manufacturers need to bring their products to the UK market.
We already have a regulatory framework for medical devices in the UK - The Medical Devices Regulations 2002 (as amended). Under those regulations, it’s possible, now, to apply through a UK Approved body, to get a UKCA marking for a medical device.
The changes we’re making will update those regulations. The legal permission to do this comes from the Medicines and Medical Devices Act 2021, and that requires us to do certain things, including undertaking a full public consultation on the changes we plan to make. These changes must be debated in both the House of Commons and the House of Lords before they’re made law.
On 9 January we published a Roadmap to give more visibility of how we’re progressing in making those regulatory changes. There’s an element of it which is looking in the rear view mirror, and it shows the public consultation undertaken in 2021 and in 2022, the publication of the government response, which set out the changes we intend to make.
Those changes are extensive, and since 2022, we’ve strengthened the team through the recruitment of team members with industry and policy backgrounds, and they’ve been working to define the detail that’s needed to turn our intentions into law and instruct lawyers through the process of creating legal text.
We’ve divided the work up into a several statutory instruments (SIs), including one we put in place last summer to give transition provisions a legal footing and one which has been debated in the last month involving the application of In Vitro Diagnostic Regulation (IVDR) to Northern Ireland.
As you’ll see from the Roadmap, our next major SI will strengthen requirements for vigilance and the surveillance of products once they’re on the market. The draft legal text of this Post Market Surveillance (PMS) SI has already been published.
We learned a lesson from the publication of the text for PMS. We know that regulations only work if the regulated sector understands them and can practically implement them. Last year we ran a number of workshops exploring the detail for the proposed PMS rules, seeking to understand what the guidance needs of industry might be. Despite this, the response to the publication of the legal text raised issues that had not come up in those sessions.
The approach set out in the Roadmap demonstrates our commitment to working even more closely with stakeholders to make sure that the links between what we said we’d do in 2022 and the detailed positions are clear, that we understand any concerns and, where possible, address them before we formally publish draft legal text and most importantly, that stakeholders know what is coming and can start to prepare.
After PMS will be a SI to put in place what we’re referring to as our 'Core' regulations - updating the fundamentals like scope, classification, some of the requirements for economic operators as well as the requirements for quality management systems. For some of these, for instance clinical investigations, a lot of the changes we’re making are already happening as best practice. For others, such as International Recognition, this is not something we’ve done before.
The Roadmap commits to stakeholder discussions on a number of issues, and we started, on 26 January, with a full day discussion on International Recognition, working through our draft proposals for a risk-based system where products that have gone through a full, rigorous assessment by a regulator with comparable standards, such as the FDA, would be subject to minimal checks before being allowed onto the UK market but importantly, required to comply with UK PMS requirements.
Some of the stakeholder engagement we’re doing, including the most recent one on International Recognition, will be under 'trusted advisor' principles, an arrangement we’ve come to whereby we can work openly to get the views of stakeholders, to inform our policy development. This blog series is a way of keeping a wider audience informed with how those sessions are going. Some sessions, however, are more open, and we’ve been delighted with the response to the webinar we’re planning on 5 March on Scope, Classification and Essential requirements.
One of the things I’m really proud of is shown in only one place in the Roadmap – It’s the continued work to designate new Approved Bodies. We announced in August the doubling of UK capacity and at the end of January we increased that capacity still further. We also wanted to make sure we included in the Roadmap the progress we’re making on clarifying the requirements for developers of Software as a Medical Device. These are all ways in which we’re contributing to the creation of a UK environment innovators want to come to, which will benefit UK patients.
I’d like 2024 to be a year of transparency. This blog series is part of that and as we work through to deliver our Roadmap, there will be more. Our priority is patient safety and we know we need to work in partnership with our stakeholders to achieve that.
]]>World AMR Awareness Week (WAAW) is an annual global campaign from 18-24 November that raises awareness and understanding of antimicrobial resistance (AMR), a global health issue worsened by the misuse of antimicrobial agents such as antibiotics.
AMR can lead to infections becoming impossible to treat, increasing the risk of severe illness and death. Below, we take a look at how experts at the Medicines and Healthcare products Regulatory Agency (MHRA) South Mimms Laboratories, are supporting the development of potentially lifesaving alternatives.
Since Sir Alexander Fleming’s chance discovery of penicillin almost 100 years ago, in some contaminated Petri dishes he forgot about on his holidays, we’ve lived safe in the knowledge that any bacterial infection can be cured with a course of antibiotics. However, through the misuse of antibiotics and other antimicrobials, we’ve unknowingly wandered into a biological arms race against bacteria a century in the making, and we’re losing.
Our overreliance on antimicrobials has accelerated the resistance of bacteria, fungi and parasites, reducing their effectiveness against infections to as little as zero in some cases. With the development of new antimicrobials being a lengthy and complex process, time is running out to find solutions to this global health issue, which is expected to be a bigger killer than cancer by 2050.
From new diagnostic techniques that ensure antibiotics are only used for bacterial infections, to new bacterial vaccines reducing the need for antimicrobial therapies, we need truly novel cross-functional approaches to tackle the problem.
Our world-leading scientists at our South Mimms Laboratories are taking a proactive approach to supporting innovation in addressing this urgent issue. Through the supply of 95% of all World Health Organization International Standards and Reference Reagents (materials that help manufacturers measure the quality of their products), we’re supporting the research and development of novel antimicrobial therapies and alternative treatments in the UK and around the world.
Our activities to support solutions to AMR include close collaboration with the emerging microbiome research community, bacteriophage innovators, novel diagnostics developers, and those making new bacterial vaccines.
The microbiome is a whole microscopic world living inside and on our bodies. The microbiome is complex and dynamic network of microorganisms, and its unique position between our bodies and the environment means it can frequently change in response to internal and external factors. These changes can have a huge impact on our health and on the effectiveness of the treatments we receive.
Harnessing the potential of this network of trillions of microorganisms could help inform the way drugs are delivered, where they’re targeted and even lead to the development of novel medicines.
The microbiome also has the potential to be a key tool in the fight against antimicrobial resistance. Research supported by our scientists has discussed how using faecal transplants to introduce good bacteria to the body, can provide an alternative treatment for bacterial infection when faced with antimicrobial resistant strains.
Despite the demonstrated potential of microbiome research to provide solutions for overcoming AMR, amongst other diseases, the field is still in its early stages, raising concerns over lack of consistency and alignment across studies. To support this, we’ve developed and manufactured DNA and whole cell standards for the microbiome, to ensure research is of the highest quality, providing assurance of the performance of assays to analyse the safety of future products.
Beyond the development of new therapies, we may have some natural allies in the fight against AMR in the form of bacterial predators called bacteriophages. These are viruses, but not as you may know them. Naturally occurring in the environment wherever bacteria exist, bacteriophages are hugely abundant and can be adapted to target specific bacteria.
Bacteriophage technology is of great interest globally and we recently contributed to the UK Parliamentary enquiry into the potential of bacteriophage therapies to tackle AMR. As part of this select committee, we highlighted the challenges and gaps in bacteriophage regulation, and what we can do to ensure their safety and effectiveness for patients.
An unexpected potential solution to AMR could come in the form of bacterial vaccines, the most well-known being outer membrane vesicle vaccines, or OMVs. By removing the internal structures within a bacterium and delivering only its shell in the form of the OMV into the body, our own immune system could raise a response and then recognise these bacteria in the future and fight infection for us.
Our use of vaccines will be vital in combating AMR, either directly by targeting infections which are resistant to antibiotics or indirectly in combination with accurate diagnostics by targeting viral diseases for which antibiotics are often wrongly prescribed. We’re also supporting vaccine innovators with investigations into novel, needle-free delivery of vaccine candidates such as those against group A and B streptococci. This could support with global accessibility to vaccines, especially in low and middle-income countries where needle-free delivery can be conducted without the need for specialist training. Through the development of new standards and quality assays, we can also provide a benchmark for manufacturers to measure vaccine effectiveness.
As the UK medicines regulator, the MHRA plays a vital role in providing guidance to support innovators through the regulatory process towards product authorisation, ensuring our high standards for quality, safety and effectiveness are met.
Regulatory guidance is based on years of research, evidence and experience, but with so many solutions to the AMR problem being new, this evidence is lacking, and regulatory guidance remains immature. A lack of guidance for innovators can create delays in assessment, increasing the time taken for novel therapies to reach patients. Time that’s swiftly running out.
To address this issue now, we’re engaging with innovators as early as possible in the development of novel treatments and diagnostics, to identify what products they’re developing so we can have the right guidance ready for them before they make a submission for authorisation.
AMR is a complex problem, and not just a human one. Therefore, the MHRA is actively working with regulators across the world to tackle it, recently joining the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR), as well as with other agencies in the UK such as the Food Standards Agency, Veterinary Medicines Directorate, and UK Health Security Agency to ensure we’re taking an holistic, One Health approach.
These activities are many and broad, so we’ve now launched our own AMR working group to bring together all the expertise from across our network at the MHRA and with our partners so we can tackle AMR together.
We want to support innovation and collaborate with scientists from around the world to deliver the highest quality scientific research and you can see examples of our work in the open access publications on our website.
]]>Dr Alison Cave, Chief Safety Officer at the Medicines and Healthcare products Regulatory Agency (MHRA) highlights how genetics could play an important role in minimising the risk of adverse drug reactions (ADRs), and how the MHRA are working with partners across the system to make this a reality with their new Yellow Card biobank.
At the MHRA, it’s vital that we identify, assess and act on ADRs to strengthen the safety of medicines and medical devices for UK patients. Last year, ADRs resulted in or contributed to 16.5% of total hospital admissions, estimated to cost the NHS in England £2.21 billion per year. Gaining a better understanding of why people have adverse reactions, therefore, may enable us to prevent ADRs and in doing so save money and, most importantly, lives.
We already know genetic factors play a significant role in many ADRs, with research suggesting that an estimated 20-30% could be prevented through pharmacogenetic testing.
This led to the NHS ambition to embed pharmacogenomics into routine clinical care by the end of the decade, in its Long Term Plan. Great strides have been made in this area already, for example, testing being available for patients before the prescription of the HIV treatment, Abacavir, and most recently the antibiotic Gentamycin.
But we need to accelerate the development of more pharmacogenomic tests. The MHRA first received a report of a potential aminoglycoside-induced ototoxicity (serious and irreversible damage to ear function caused by antibiotics such as Gentamycin), over 50 years ago. 20 years later, the MT-RNR1 m.1555A>G gene variant was confirmed as a genetic cause for this reaction, and this year, NICE provisionally approved a bedside test for infants at risk of sepsis, to help reduce the number of severe reactions to a drug that could save their lives, and is expected to save the NHS £5-7m per year. But it took nearly 50 years to translate that first Yellow Card report into a bedside diagnostic test.
Abacavir was first approved for HIV in 1999 but up to 12% of patients suffered severe hypersensitivity, an allergic reaction which can prove fatal. Over a decade later, the hypersensitivity was linked to the HLA-B*5701 allele and subsequent analysis showed that testing for the allele reduced incidences of hypersensitivity to <2%. Today, all UK patients need to be pre-tested for HLA-B*5701 prior to prescription of Abacavir.
However, to make examples like these more mainstream, we need to identify the genomic markers that put people most at risk of specific side effects, so that we can identify those patients most likely to suffer harm while maintaining access to life-saving medications for those at lowest risk and who can benefit most. Ultimately, with a better understanding of genetics, we can deliver on the vision of precision medicine, with treatments tailored to the unique needs of each individual.
This is why, in June this year, we launched a pilot of the Yellow Card biobank, in collaboration with Genomics England. The biobank will support our work towards more personalised treatment approaches, by ultimately housing a repository of pseudonymised genetic information linked to healthcare information, to enable researchers to determine whether an ADR was caused by a specific genetic trait. Doctors in the UK could then screen for specific genetic traits to ensure patients receive the safest medication for them.
The biobank will use the Yellow Card Scheme to help identify patients who have suffered a specific ADR. The Yellow Card scheme is our flagship system for collecting information on safety concerns, including suspected side effects or adverse incidents involving medicines, vaccines and medical devices. Set up in 1964, it forms a critical part of the well-established systems and procedures in place for vigilance in the UK and now holds information on over 1.5 million suspected ADR reports. Using this information, with appropriate consent, we will be able to identify and approach patients who have suffered specific ADRs to invite them to participate in the Yellow Card biobank.
The initial phase of the pilot will concentrate on a medicine called Allopurinol, used to treat gout, kidney stones and other types of kidney problems, and the related but rare side effect of severe skin reactions, including Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
Participant recruitment will begin in November, and once enrolled, they will be visited at home by a nurse, who will take a blood sample that will be added to the biobank and genetically sequenced. Data will be de-identified and added to a secure research environment led and managed by Genomics England, with initial findings from the pilot due to be published in 2025.
Ultimately the information collected could transform the way we manage side-effects of medicines by allowing us to prevent ADRs, thus easing the burden on the NHS and making medicines safer for everyone.
Our hope is that the biobank will become a valuable resource for pharmacogenomic research in the UK by ensuring patients receive the safest medicine for them.
If you’re a healthcare professional who has submitted a Yellow Card report on behalf of a patient, relevant to a research topic in the pilot, we may ask for your assistance contacting them to see whether they would be interested in participating.
If you’re a patient who has submitted a Yellow Card report relevant to a research topic in the pilot, we may follow up with you directly to see if you’d be interested in volunteering to participate.
]]>As a nurse, I always endeavoured to keep myself informed about the medicines and devices I used with patients but understood very little about the process that put them in front of me or monitored their safety once they were on the market. I trusted they were safe and effective but never thought about how this was ensured or how I could help.
I’ve spent the last few years working as a benefit risk assessor at the Medicines and Healthcare products Regulatory Agency, the body that regulates medicines, medical devices and healthcare products in the UK, initially reviewing the post-market surveillance for medical devices and more recently leading a project on digital mental health regulation. This turn in my career has allowed me to learn exactly how patient safety is supported in the UK.
All medicines and medical devices have to go through a robust safety assessment before they are approved for use in the UK, with manufacturers having to provide not just clinical trial and safety studies to support their claims for safety and efficacy but also open for inspections of their manufacturing facilities and distribution networks, to ensure that every single step of the supply chain is protected for patients.
Once products are on the market, though, this work doesn’t stop as ongoing monitoring is crucial in ensuring they remain safe. There are many factors that can impact this. Manufacturing processes can change, long-term effects on both patient health and product resilience can become evident, and effects on under-represented demographic populations in safety studies can be seen once the product reaches a wider population, amongst others.
At the MHRA, we conduct extensive post-market surveillance which brings information in from a wide range of sources so that we can identify potential safety signals with medicines and devices, evaluate the benefit risk impact and then develop risk minimisation measures, preferably in collaboration with manufacturers and market authorisation holders, to maintain the safe use of healthcare products.
Manufacturers are required to maintain a continuous feedback loop on safety and efficacy evidence once their product is licensed in the UK, and they have to report this data to the MHRA if safety concerns become evident. We can also use information from other sources such as new post-market safety studies, other regulatory bodies, anonymised data from electronic healthcare records, whistle-blowers and, most importantly, reports from our Yellow Card scheme.
The Yellow Card scheme is the MHRA’s flagship system for collecting information on safety concerns, including suspected side effects or adverse incidents involving medicines, vaccines and medical devices. Set up in 1964, it forms a critical part of the well-established systems and procedures in place for vigilance in the UK.
The scheme relies on voluntary reporting from patients and healthcare professionals like you, receiving and processing almost 100k reports relating to medicines and devices a year. This is crucial in helping to provide an early warning that the safety of a healthcare product may require further investigation. In turn, this helps us to identify potential signals that were previously unknown before being reported.
Every single Yellow Card report submitted to us is analysed by experts, including doctors, pharmacists, scientists, medical device specialists and nurses, like myself. When we combine them with all the other sources of data, like those above, it helps us to determine what events may be a potential signal and what may have occurred anyway, in the absence of the medical intervention.
This is significant because to report a Yellow Card, you only need to suspect a potential link between the product and the event, but sometimes further investigation shows that the issue being reported is not due to the medicine or medical device in question.
This is why it is so important to report. I know from experience that nurses are in a fantastic position to advocate for the safety and efficacy of medicines and medical devices as you are most likely to be administering medications, using medical devices and monitoring for side effects.
While I know that nursing comes with a heavy load of mandatory reports, should an adverse event or reaction occur, it’s really important that the information is shared with us, so we can build a picture of emerging trends that can then be pro-actively managed. By doing so, you are directly helping to keep your patients safe.
To make things smoother, you could add the Yellow Card app or website into your incident reporting tools on the wards, so it becomes part of the process you use each time.
Patient and healthcare professional insight really does make a huge difference to our assessments and they can influence our regulatory decisions.
Whether you work on a ward or in the community, by promoting the Yellow Card scheme to your colleagues and patients, you’ll also help us to raise awareness of how to report safety concerns and strengthen our vigilance systems that support safety for all patients.
Reports from healthcare professionals help us to monitor the safety of healthcare products once they are on the market and have already helped us to identify numerous safety issues.
A potential link between ranitidine and breast conditions such as gynaecomastia and galactorrhoea was uncovered following Yellow Card reports from two clinicians. Following an extensive investigation and analysis of the evidence, this ultimately led to strengthened warnings and new side effects listed in the Patient Information Leaflet.
It’s therefore vitally important to flag any potential side-effects that patients report to you.
You can do this quickly and easily through any EMIS, SystmOne or Vision system or use the Yellow Card app or website.
Without accurate, timely data, our monitoring is always going to be less effective. Every time you make a report or support your patient to make one, you are directly helping to improve the safety of these products for everyone.
We are here to support you in this. There is more information and many resources such as accredited e-learning modules (developed in partnership with Nursing Times and worth 2 hours CPD!) as well as materials like posters and patient information cards available on the Yellow Card website and through the regional Yellow Card centres.
We’d encourage you to sign up to receive our Drug Safety Updates, or download the Yellow Card app from the Google Play Store or Apple App Store to get them directly to your phone so you can stay up to date with the latest in medicines and devices safety information, as well as quickly and easily make a report, see if there are any other reports about that drug or device and track your report through the assessment system.
If you want to know more about the Yellow Card scheme and how to get involved, we’ll be exhibiting at the HSJ Patient Safety Congress in Manchester (18-19 September 2023). If you’re attending, come and see us to find out more about our plans for the future of the system and feedback your experience with it.
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Following the COVID-19 pandemic, health systems have made great progress in developing safe and effective vaccines and delivering them to people across the world. However, while the world was focused on COVID, other viruses did not go away. This World Immunisation Week, the World Health Organisation (WHO) is collaborating with global partners for ‘The Big Catch-up’ to address what they estimate to be 30 years of vaccination progress lost due to the COVID-19 pandemic.
In the UK, NHS data for the year 2021/22 showed that, for the first time since 2010/11, the 95% national vaccine coverage target for children under the age of five was not met. And this week, UKHSA’s latest update showed an equally concerning drop of 7% in uptake for adolescents receiving the vaccine protecting against tetanus, diphtheria and polio in 2021/22 compared with the previous year.
We are therefore encouraged by the findings from a recent survey reported by the Meningitis Now, finding that over 90% of parents of under-fives trust vaccines and believe they are safe and effective and three quarters of parents surveyed said they had heard or seen something that made them feel it was important to have their child vaccinated.
From smallpox and flu to meningitis and HPV, vaccines have been the most effective way to boost immunity and fight viruses for generations.
At the MHRA, we are committed to helping all parents and healthcare professionals have confidence that the vaccines being delivered in the UK are effective against disease and safe for use by the general public and the most vulnerable, including our children.
We also know that children have unique needs that must be considered when assessing the safety of vaccines, such as whether the dose and route of administration are appropriate.
Therefore, long before a vaccine reaches a child or is added to the routine childhood immunisation schedule, we are involved in testing and monitoring a vaccine’s development.
This starts when researchers apply to us for authorisation of their clinical trial, where we review how it will be conducted, whether it will provide useful information and whether we think it is safe to conduct. Over the past 5 years, we have assessed and authorised over 4,000 clinical trials in the UK, supporting innovation and ensuring the safety of the public is always front of mind.
Throughout clinical trials, all side effects must be reported so we can assess the benefits and risks before making a recommendation for how the trial should proceed, if at all.
At completion, we thoroughly review all the data from the lab and clinical trial results as well as manufacturing and quality controls. Once reviewed, we then seek advice from the independent Commission on Human Medicines, who also assess the data before advising the government on the safety, quality and effectiveness of any potential vaccine.
Following these assessments, we provide reports including a Summary of Product Characteristics, giving healthcare professionals a description of a vaccine’s properties and the conditions attached to its use. We also provide a Patient Information Leaflet on using the medicine safely and share a Public Assessment Report explaining how each product was assessed and authorised.
After we approve a vaccine for children, we continue to monitor it. We test every single batch of vaccines in the UK to ensure that each one is exactly the same as the one we approved before it can go to the health centres that immunise your child.
Our role doesn’t stop there. We constantly collaborate with healthcare authorities around the world, sharing information to monitor a vaccine’s effectiveness and remain vigilant for any potential safety concerns. Our most important partner in that, is you.
The Yellow Card Reporting Scheme is our system that allows you to flag any suspected side effects with a medicine, vaccine or medical device. We encourage everyone to monitor any side effects and report them immediately to us. Reports are reviewed by our safety experts who analyse the risks and then make a recommendation for any necessary updates to the safety information or how the vaccine is used in children.
Reporting by parents and adolescents through the Yellow Card Reporting Scheme, combined with reports from healthcare professionals and other data sources, means we are able to continuously monitor and review vaccine safety and act quickly to protect public health.
As the WHO aims to deliver ‘The Big Catch-up’, the MHRA will continue working with researchers, healthcare authorities and the public to make sure safety and quality standards are met from trials to clinics, to ensure vaccine safety for our children at every step.
]]>On this day in 1948, the United Nations (UN) came together to establish a global organisation that promotes health, keeps the world safe, and serves the vulnerable. Seven decades later, the World Health Organization (WHO) is celebrating its 75th anniversary. To mark the occasion, the WHO is using this World Health Day to raise awareness of its journey towards ‘Health For All’ by looking back at its greatest achievements and looking forward to how current challenges could be addressed.
From the eradication of smallpox in 1980 to the interruption of wild poliovirus in Africa in 2020, the WHO has always been at the forefront of protecting and promoting global health. We have been proud to collaborate with the WHO over the years, supporting their efforts from research and expert counsel, to ensuring the quality and safety of medical products for patients and families around the world.
Many WHO successes over the past 75 years have involved the development and delivery of biological medicines. These are any medicinal products that come from a living source such as a virus or bacterium, like a vaccine, which we’ve all become more than familiar with in recent years. Due to differences in their nature and how they are made, biological medicines are regulated, tested and controlled differently compared to other medicines. This is where the WHO come in, setting requirements for manufacturing and regulations to help assure their quality, safety and effectiveness. Through its collaborating centres, including the MHRA, the WHO also establishes WHO International Standards that are used to help ensure the consistency of biological products across different batches around the world.
MHRA is the leading WHO collaborating centre and international laboratory for biological standards, developing, producing and supplying over 95% of all WHO Standards. The almost 400 different international standards and references we have available ensure that healthcare professionals and the patients they support can be confident in the quality of the medicines they are using.
One of the most widely distributed biological medicines worldwide each year is the influenza vaccine. Influenza is constantly changing and mutating, meaning it can easily evade the immune system. We have been working on influenza for many decades and as an Essential Regulatory Laboratory (ERL) we collaborate with the WHO and the other three ERLs to prepare for every influenza season. This starts with reviewing data collected over the previous winter months to identify which flu strains have been most prevalent. An expert panel, including a representative from MHRA, then meets in February to select which strains are most appropriate for the development of vaccines for the upcoming northern hemisphere season (the same process happens in September for the southern hemisphere influenza season). The latest recommendations from this most recent meeting have just been announced.
With immunisations of at-risk groups taking place in the autumn, vaccines need to be developed in half a year, 20-times faster than the usual 10-year timeline. The MHRA is essential to ensuring this deadline is met by developing candidate vaccine viruses (CVVs). These CVVs are viruses that match the selected influenza strains each year but grow much better, enabling manufacturers worldwide to develop the required amount of vaccine in the time available. Once produced, we need to confirm that the vaccine works and that it meets specifications using a vaccine potency test developed by our experts (in what was then known as NIBSC) in the 1970s, which is still the gold standard today. This potency test requires the use of two types of reagents, an antigen standard and an antiserum. These reagents are produced by the MHRA and the other ERLs and distributed to vaccine manufacturers and independent control laboratories worldwide. Once all the processes have been completed, the influenza vaccine is ready to be delivered.
While influenza continues to be a yearly concern for the WHO and MHRA, a little further from home, our collaboration is close to making polio a disease of the past. In 1988, almost 1,000 children per day were paralysed by polio globally; now, due to better detection and mass vaccination programmes, led by the WHO Global Polio Eradication Initiative, the wild form of polio has been eradicated in all but two countries. However, polio remains a concern, and in fact, research conducted by MHRA scientists 25 years ago described the first known example of a vaccine used to control polio spreading widely and being responsible for new cases emerging.
The oral polio vaccine (OPV) has been largely responsible for the eradication of polio and contains a weakened version of the poliovirus. It is cheap and easy to use and reduces infection risk without the need for injection. However, in an under-vaccinated population, if the weakened virus is passed between unvaccinated people enough times, its ability to cause paralysis can be reactivated. In recent years MHRA research has looked into ways of developing OPVs that do not have the ability to reactivate.
There is another form of the vaccine being used in Europe and North America, made by growing large amounts of poliovirus in tanks and then killing it completely before producing a safe vaccine that can be injected. But in a world where polio is almost gone, how can we produce huge vats of virus safely around the world without it escaping and returning? As a WHO collaborating centre for reference & research on poliomyelitis, MHRA hopes to answer questions such as these and support final eradication efforts.
Many of us won’t remember a time before WHO, and thanks to their efforts, more people are born each day into a world where the health of our global population is continuing to improve. We are proud to have collaborated with the WHO throughout the years and look forward to continuing to face global challenges with them to achieve ‘Health For All’.
]]>Funders, regulators, and research organisations had come together to share a powerful message with the research community. Public involvement is important, expected, and possible in all types of health and social care research. This felt big.
One year on, I am now working at the Medicines and Healthcare products Regulatory Authority (MHRA). The shared commitment aligns well with our agency’s ambition to put patients first and is supporting us to deliver against our Patient Involvement Strategy.
We have been involving patients in the Innovative Licensing Access Pathway. This pathway aims to reduce the time it takes for new medicines to be brought to market. This will give patients faster access. Patients are involved in the Steering Group (part of the governance structure). This group reviews applications from medicine developers to access the pathway. Patients’ valuable expertise and insight helps with the decision on whether to accept an application to the pathway.
As a regulator, we have an important role to play to influence the research landscape. In the Innovative Licensing Access Pathway, we share the patient insights back to the medicine developer, so they can use these insights in their work. We encourage the developer to engage with a wider range of patient groups for diverse input, and to consider Patient Reported Outcomes and other measures to ensure the medicines in development offer the best outcomes for patients.
We are not just committed to public involvement in research, but also across the regulatory pathway. One example is when a Hormone Replacement Therapy (HRT) was reclassified from a prescription-only medicine to pharmacy medicine, giving people experiencing menopause better access to treatment. A key factor in the reclassification process was focussing on issues that matter to patients, and over 1000 members of the public gave their views during our consultation.
We have made changes to how we run our consultations, to support more people to respond. These are working well – the response to the HRT was the highest response we have ever received to a public consultation (the previous highest was 251). Small changes, such as how we promote our consultations to relevant audiences, so the right people know about it, are having an important impact.
These steps create a good foundation, but we know we have much more to do to ensure the patient voice is embedded across the regulatory pathway. My personal commitment is to prioritise diversity and inclusion within our patient involvement, to support equity within health and care.
I would like to say thanks to each member of the public, patients and patient groups who have contribute their lived experience to our work.
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