Commons motion to approve the draft Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 - Feb 19

I beg to move,

 

That the draft Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019, which were laid before this House on 23 January, be approved.

 

Before I discuss the regulations, it is important to reiterate that we wish to retain the closest possible working partnership with the EU to ensure that those engaged in clinical trials can continue to develop innovative and cost-effective treatments and that patients recruited in trials can continue to have timely access to medicines. However, we are bringing forward this legislation to continue preparations for no deal, in case we need to be prepared for that eventuality.

 

In developing this amending legislation, my Department’s priorities have been to minimise any disruption to ongoing trials and to make sure that the UK regulator can still protect public health and, importantly, that the UK’s biomedical, health and life sciences research sectors can continue to be world-leading. With that in mind, the Medicines and Healthcare Products Regulatory Authority has sought to take a pragmatic and proportionate approach in establishing the new regulatory requirements. Importantly, that has been done through continued close co-operation with stakeholders. After a period of informal consultation in August, the MHRA published an initial proposal, and it followed that up with further consultation. The feedback from that consultation, which received over 170 responses, led to the statutory instrument before us.

 

Let me bring a few details to the attention of the House. First, wherever possible, we have sought to maintain existing arrangements. Given that the system for clinical trials is currently based on national-level decision making in the EU and globally, we have not had to make any substantial change in some key areas. In particular, on the ability of the UK to participate in multinational trials in the EU or in the rest of the world, there will be no change. Also, the data gained from trials in the UK can still be deposited in international repositories and be accessed by others. I think the House will agree that that reflects our approach, which is to continue multinational co-operation on clinical trials.

 

In other areas, we have faced a choice regarding the UK’s regulatory requirements. In those instances, we have sought to maintain current arrangements, provided that the regulator still has sufficient ability to protect public health. For example, we will continue to recognise existing approvals, so there will be no need to reapply for both regulatory and ethics approvals. We will have the same information requirements as the EU for any new applications for multi-state trials in the UK. There is also a requirement that a clinical trial sponsor or legal representative for clinical trials in the EU should be based in the EU. That will ensure continuity of the existing clinical trials landscape and maintain the UK as an attractive, open environment in which to conduct clinical trials.

The Minister is making an important speech. Does she recognise industry concerns about the introduction of an extra level of regulation through the proposals for a qualified person requirement? There is a worry that it will make our country a less attractive place to conduct clinical trials, which are, of course, extremely important to my part of the world.

I appreciate the hon. Gentleman’s point. Perhaps I can reassure him by emphasising that the UK is committed to establishing a far-reaching science and innovation pact with the EU to facilitate the exchange of research and ideas, so we continue to maintain the competitiveness to which he refers.

 

In bringing forward these proposals, we have been determined to establish our pattern of regulation from outside the EU if need be, but as much as possible we wish to continue with business as usual. We will continue to engage with the sector to maintain competitiveness, because we fully appreciate the value of the life sciences sector to our economy.

Paragraphs 7.6 and 7.7 of the explanatory notes highlight that the EU makes information public and transparent. They talk about the MHRA doing that, but they do not mention that the MHRA would be publishing data within the upcoming EU system.

The regulations are determined to facilitate transfer with not only EU bodies, but internationally. We fully recognise that in bringing forward the regulations we are operating in an international landscape. The regulations are designed to facilitate that co-operation, as well as to establish the MHRA as the lead regulator. It is worth noting that, within the current system, the MHRA is the lead. In terms of the regulation we are transposing, rather less is coming to the MHRA given the existing ownership it has in this field.

Given that our industry is a world leader and a very significant part of the European effort, does the Minister see opportunities in the future for us to have world-class regulation where we lead and differentiate in a way that would strengthen our efforts?

My objective this afternoon is to make sure we can continue with business as usual on exiting the European Union, but clearly once we have left the European Union that would be open to us. The ethos behind the regulations and the consultation we have had with the sector very much recognises that this is an international market place. We must ensure that in taking forward these requirements we remain competitive.

 

As I was saying, we will require the same information requirements as the EU for any new applications for multi-state trials in the UK. There is a requirement that a clinical trial sponsor should be based in the EU. There are a few areas where it has been necessary to add a new requirement, as a result of the UK no longer being part of the European regulatory framework, relating to the MHRA putting in place a new national IT system for safety reporting and submissions. In addition, investigational medicinal products, known as IMPs, imported from the European Economic Area will now require an import licence, as they would no longer be part of the single market. As the hon. Member for Central Ayrshire (Dr Whitford) said, they will be overseen by a qualified person to ensure that the products are appropriately certified. That builds on the existing import licensing system, which allows the transport of IMPs direct from the EEA to UK trial sites to continue. Recognising that this is a new system, we have provided stakeholders with a 12-month transition period from exit day before it comes into force.

 

While not specifically covered in this statutory instrument, I would like to reassure Members that the Government are engaging with organisations running clinical trials to ensure continuity of supply and that drugs continue to be received. The Government are undertaking a comprehensive deep dive into clinical trial supplies to gain detailed understanding of what is required, and are putting place contingency plans in case the sponsors need them. They will include access to the same prioritised shipping routes that will be available for all other medicines.

 

As I mentioned in response to the hon. Member for Cambridge (Daniel Zeichner), the Government are committed to ensuring that the UK remains one of the best places in the world for science and innovation. Members should note the Government’s commitment to aligning with the EU’s new clinical trials regulation as far as we can, without delay, when it does come into force, subject to the usual parliamentary approvals.

Will the Minister also comment on the concerns raised by organisations such as Cancer Research UK about future pan-European trials, for which it would appear that the sponsor or lead would have to be from within the EU rather than within the UK?

As I said in response to earlier questions, the Government’s approach is that this an international marketplace. We clearly want access to the best possible medicines and to ensure that we can continue to co-operate and share that information as best as possible. I fully expect the MHRA to share that information with the European regulators, as it currently does. Regardless of EU exit, the MHRA and partners across the UK healthcare ecosystem are already taking steps to improve the UK clinical trials application process to ensure that it is as seamless as it can be.

 

In conclusion, in the event of a no deal, these regulations will put in place a pragmatic solution that ensures that the UK’s clinical trials legislation continues to function effectively after exit day. Essentially, we want this to be business as usual following exit, and I commend this statutory instrument to the House.

I thank the Minister for bringing this legislation to the Floor of the House and for providing us with a summary of it, which helped immensely. We are expecting many more health SIs in the weeks to come, so I must make it clear again, as I will in future, that it is incredibly concerning that we are now only 38 days away from 29 March and are still preparing for a no-deal Brexit. I hope that it does not come to that, but this has taken up a considerable amount of Parliament’s time and resources. My preferred scenario would have been one in which the Prime Minister did not run down the clock for two years, and especially now when we are getting closer and closer to Brexit day. I understand the need for “just in case” legislation, but we should have secured a deal by now.

 

Moving on to the legislation, clinical trials will probably not be in the forefront of people’s minds, but they are crucial for the safety and efficacy of medicines, as well as for our health and wellbeing. Medicine is not something that we should get wrong, but when we do, as in the case of Primodos, valproate and vaginal mesh as a surgical procedure, we must hold up our hands and take urgent action.

 

While this may not be the most eye-catching statutory instrument, it is hugely important. It is about patient safety and confidence. It would mean that in a no-deal scenario, the Medicines and Healthcare Products Regulatory Agency would be able to operate as a regulator outside the EU system and would therefore take on roles formerly conducted by the European Medicines Agency and through the wider EU regulatory framework. I must put on record my disappointment that the EMA is relocating from the UK to the Netherlands next month because of Brexit. Our loss is the Netherlands’ gain, but we should not have let it come to this. However, this SI means that in the event of a no-deal Brexit, the MHRA will be able to regulate clinical trials to ensure that they continue to operate effectively.

 

I want to ask the Minister for clarification on a few points. The new EU clinical trials regulation was introduced in April 2014 and was expected to come into force in October 2018. I understand that owing to technical issues that has now been delayed. The Government’s no-deal guidance says that

 

“we’ll align where possible with the CTR without delay when it does come into force in the EU”.

 

Will the Minister please restate that commitment to the House today?

 

If the UK does leave with a deal, which I hope we do, what will the arrangements be for the CTR and the UK? Could the UK, no longer being a part of the EMA, delay the availability of new medicines in the UK? I am aware of concerns raised that, because the UK will be seen as a smaller market for new drugs than the EU, companies will be more likely to prioritise the authorisation of new drugs in the EU rather than in the UK. Has the Minister made any assessment of this risk?

 

Will the Minister please tell the House what the implications of a no deal would be for clinical researchers who are EU nationals? Will the UK also be eligible for EU funding for clinical trials under a no-deal scenario? The UK is currently one of the largest recipients of funding for clinical trials, and I am concerned about the implications for future trials and opportunities. The MHRA will have the power to publish its own guidance on clinical trial applications and applications for an ethics committee opinion, as well as declarations of the end of clinical trials and the content of documents forming trial master files. Could the MHRA continue to work with EU states in order to keep regulation in line with the EU? Will the Minister review important details, such as ethics, where concerns are raised?

 

In July 2017, the then Health Minister, Lord O’Shaughnessy, said that in the event of a no deal the Government would ensure that any system put in place would not impose additional bureaucratic burdens. Can the Minister reaffirm this commitment today? I know that this instrument was subject to consultation and that because of concerns raised amendments were made. Will she please say whether any further amendments are expected and whether there will be further consultation? Finally, will she please confirm that any changes made by the instrument will be communicated effectively to stakeholders in a timely manner?

As we all know, Europe is the biggest research network in the world—bigger than China and America; and the UK and, within the UK, Scotland have been major beneficiaries. As the shadow Health Minister mentioned, the EMA provides a single licensing system, and countries outside Europe that are not major economies, such as Canada and Australia, face a delay of six months to a year in accessing and licensing new drugs. The EMA is not just a licensing body, however; it also funds and promotes research, particularly into rare conditions and childhood diseases.

 

Europe created the comprehensive trial regulation system with the clinical trials directive in 2001 and the good clinical practice directive in 2005. As mentioned, however, in 2014 a new directive introduced the EU clinical trials information system and the new trials regulation system, which will be under the control of the EMA when it comes into force next year. The system will provide a single portal for sponsors to register, collaborate and analyse their work and will provide work spaces for authorities and a public site that will tell patients what trials are going on and what their benefits are. It will also contain the EudraVigilance database on medicinal products that are not yet licensed, which is critical during initial trials.

 

The MHRA will take on the full role of clinical trial regulation, including legislative functions currently carried out by EU bodies, which will obviously mean additional work and costs for the MHRA. I welcome the Government’s commitment to align closely with the new European regulations, but this is not the same as being part of a single collaborative system. I note that the UK Government plan to recognise sponsors in the EEA, since EEA states will be recognised as approved countries—this is one of the amendments made—to minimise upheaval, but that means there will not be any compulsion to have a legal representative or lead researcher here in the UK.

 

Clinical trials sponsors must report any suspected unexpected serious adverse reactions—SUSARs, as they are known—to the EU database. They can currently do that from the United Kingdom, in a straightforward fashion. Similarly, any SUSARs registered elsewhere in Europe are entered in the database, so that concerns are highlighted at the earliest point during trials. Many of us will remember safety trials carried out on human subjects that resulted in major damage. It is critical that the UK does not operate in a vacuum.

 

Before licensing, particularly in the early stages of safety, dosage or phase 1 trials, investigational medicinal products are used. Those products are unlicensed, and, as the Minister said, they must be certified by a qualified person based in the EEA. If they are made in the EEA or in a third country, that is critical. For IMPs made in a third country, the importer must have a manufacturing and importation authorisation, and must ensure that a qualified person certifies the products before supplying it.

 

Unfortunately, the regulations mean that bringing a drug into the UK for the purpose of a Europe-wide trial and exporting an IMP to Europe from a UK pharmaceutical firm will introduce bureaucracy. It is bizarre to claim that there will be no additional bureaucracy. The regulations merely describe the extra licences that will be required. The MHRA will publish data on UK trials, but there is no promise that they will also be posted on the EU trials information system.

 

Simply creating something separate will not replace our collaboration across Europe. We are seeing duplication, obstruction and expense. I am sorry to say that those are all the enemies of collaboration—and that defines the loss that is Brexit.

Let me start by thanking the Department for an actual impact assessment. I have attended too many debates on statutory instruments when there has been no impact assessment. At least we know what we are talking about on this occasion, and I congratulate the Department on that.

 

I shall make three very brief points to which I hope the Minister will be able to respond. First, the headquarters of two of the top 10 pharma companies, GlaxoSmithKline and AstraZeneca, are in the United Kingdom. That matters, because there is considerable evidence that the location of the headquarters is the location of much of the investment in clinical trials. We need to maintain that hegemony, and ensure that we keep those trials here. How do the Government intend to guarantee investment in both the industry and the clinical trials?

 

Secondly, the industry is very concentrated. I know more about animal medicines, because of my involvement with the shadow DEFRA team. For instance, it was decided that the trial of the bovine tuberculosis vaccines for badgers had to end because the vaccines were needed for human use. There was one major company in Paris. That shows what the industry is really like, and that is why I fear that if we do not get this right, it will drift to other parts of the EU and we will lose out.

 

My third point is about barriers. This is not just about physical resources, the drugs and chemicals themselves; it is about people. We might find ourselves in a very difficult position, particularly if we were to crash out, heaven forbid. How does the Minister intend to ensure that, in such an event, the key people will be able to secure transferability between the UK and the rest of the EU? That issue is heightened by the enormous pressure on the MHRA in connection with a crash-out. It would be useful to know from the Minister what we will do on the people side to ensure that we genuinely defend the industry.

 

There is important health investment in pharma companies in my constituency, as there is in many other constituencies. It really does matter to us all to know that there is some certainty in what is a very uncertain process.

I thank all hon. Members who have participated in this debate, which has demonstrated how vital it is that we make sure the legislative underpinning of clinical trials continues safely, as the hon. Member for Washington and Sunderland West (Mrs Hodgson) outlined in her opening comments. That is by far our biggest priority: we need to continue business as usual, and to value our important pharmaceutical and life sciences sector and guarantee people’s safety.

 

I will try to address some of the points made today. The hon. Lady mentioned the clinical trials regulation and what it would mean in terms of adoption by the UK if it was implemented after March 2019. We expect the clinical trials regulation to be implemented in late 2020, and the MHRA, the National Institute for Health Research and the NHS have been working towards the implementation of that regulation since it was agreed in 2014. The withdrawal agreement Bill will give effect to the implementation period in domestic law and will allow EU regulations to continue to apply directly in the UK for this time-limited period. If the clinical trials regulation comes into force during the implementation period, as it is currently expected to, we would expect to apply that to the UK. If however we leave without a deal—this is why we have these regulations—the CTR will not be in force in the EU at that time so will not be incorporated into UK law on exit day; however, we intend to align, where possible, with the CTR without delay when it does come into force, subject of course to the usual parliamentary approvals. But that alignment will happen after 29 March 2019.

 

The two key elements of the regulation that are outside the UK’s control and that this instrument does not therefore cover are the use of the shared central IT portal, as mentioned by the hon. Member for Central Ayrshire (Dr Whitford), and participation in the single assessment model, both of which will require negotiated UK-EU agreement regarding UK involvement post-Brexit. This reiterates the wish expressed by the hon. Lady and shared by me that it would be far preferable if we can leave the EU with a deal. Sadly, experience tells us that these things always go to the wire, but let us hope we get a resolution sooner rather than later.

 

The hon. Lady also mentioned patient safety. Currently a sponsor can report a suspected unexpected serious adverse reaction—SUSAR—during the course of a clinical trial through the EU database. Similarly, all SUSARs originating outside the UK where the sponsor has an ongoing trial in the UK involving the same medical products currently must be entered on the EU database, and we will clearly need to find a way of entering that so we can share such information and have arrangements for holding it on the MHRA database.

Does that mean that that ability is not there if the UK leaves without a deal, for April of this year?

Being brutally honest with the hon. Lady, and perhaps more honest than some are in this debate, I do not think we can dictate terms to our EU partners; I think we can look forward to having constructive working arrangements with them and it is in all our interests to do so, but ultimately we would have to seek agreement about this. At this stage this SI can only really cover the things that are in the gift of this Government, and a lot will rest on good co-operation after the event, which again means it would be much more preferable to leave with a deal.

Given the great importance of joint venture companies and joint investment and joint activity across the Atlantic, will the Government also be looking at changes in American regulation to see if any of that would be appropriate—or maybe a UK version could be better than both the American and EU ones?

My purpose this afternoon is to ensure that we have business as usual post-exit day, and that we can maintain patient safety at that time. I would not want to encroach on any debate beyond that now.

 

Questions were raised regarding research funding. I should advise the House that before the Brexit vote the UK was involved in more EU-funded science projects than any other country. The UK secured 14.3% of the total share of the funding to date and is the second-highest recipient of grant funding. We are committed to remaining a world leader in science and research, and that is why, in our modern industrial strategy, we have committed to spending 2.5% of our GDP on research and development by 2027. We have invested an extra £7 billion in research and development as a first step towards that.

My hon. Friend has said that just over 14% was received by this country from EU funds. Does she have the figures to hand—I would not blame her if she did not—for the percentage of funds that we gave to the EU to be distributed around the bloc?

I do not have a detailed knowledge of the accounts in that regard. I can only tell the House how much we have received, and how we are replacing it, which is really the crux of the matter.

 

Mention was also made of what the Government are doing to prevent the loss of EU nationals working in research. We have been clear that we wish the UK to continue to be an open and tolerant nation, and to continue to attract the brightest and the best. That is equally applicable here. The Prime Minister told the House of Commons on 21 January:

 

“Having listened to concerns”

 

about the settled status scheme

 

“I can confirm today that, when we roll out the scheme…the Government will waive the application fee”.—[Official Report, 21 January 2019; Vol. 653, c. 27.]

 

We want to give a clear message that we are open for business and open to the brightest and the best.

 

In bringing these regulations to the House, the central point is that the fundamentals of how clinical trials operate will remain the same and that, wherever possible, we have sought to maintain existing arrangements rather than creating new ones. While it is not the focus of this statutory instrument, the Government are working to ensure that the trials have continuity of supply and will continue as planned. I commend these orders to the House.

 

Question put and agreed to.

 

Resolved,

 

That the draft Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019, which were laid before this House on 23 January, be approved.