Pharma Execs Flag Up More Brexit Regulatory Woes – And A Possible Solution
Executive Summary
Pharma executives painted a rather bleak picture of a UK regulatory system cast adrift by a hard Brexit, with problems likely in areas such as drug approvals, clinical trials and the role of the MHRA. One solution was proposed, however, to avoid the need for a free-standing UK approvals system for new drugs.
The pharmaceutical industry has made it clear since the Brexit vote that its preferred option is a regulatory cooperation agreement between the UK and EU in order to avoid problems in areas including but not limited to drug approvals, clinical trials and batch release.
While it’s still not known what the outcome of the Brexit talks will be, the worst-case assumption at present is that the UK becomes a third country and may need to set up its own regulatory system to approve innovative drugs that in the EU are submitted, evaluated and authorized centrally.
Just how that might be done, and how much it might require in terms of personnel and money, is still far from clear. One possibility has been put forward by Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry, who said the idea had buy-in from the UK government.
Speaking at yesterday’s hearing of the House of Commons business, energy and industrial strategy committee, Thompson described the proposed solution. The first stage would be the scientific review of a new drug submitted for centralized authorization by the European Medicines Agency’s scientific committee, the CHMP. As with the current system, the committee’s opinion would then be sent to the European Commission for a final decision on marketing authorization; critically though, it would also go to the Medicines and Healthcare Products Agency for a final decision on UK approval.
London would be able to say ‘we have full control over the medicines we license for UK patients’ – ABPI’s Mike Thompson
“If the decision train is split in two, and one half goes to Brussels and one half goes to London, the advantage would be that London would be able to say ‘we have full control over the medicines we license for UK patients,’ and Europe would be able to say ‘we control what we license,’” Thompson told the committee. “Taking back control” and avoiding oversight of the Court of Justice of the EU are of course two of the key demands of Brexit supporters.
The benefit to the UK “is that the decision would not be beholden to the ECJ, but the result would be that the medicines used across Europe would be identical,” he said. “We know that this is acceptable to the UK government, and we believe it would be acceptable to Europeans too.”
This kind of regulatory cooperation “obviously would also fit the Irish question because that meets some of the requirements that people are looking for there,” Thompson said, referring to the difficulty of finding a solution to the likely effects of Brexit on the border between Northern Ireland and the Republic of Ireland.
Mutual Recognition?
Another possibility, if the MHRA can no longer play a role in the EU regulatory system and has to establish a stand-alone regulatory regime, is to have a system of mutual recognition of decisions taken by other regulators, Thompson suggested.
The way the EU system works at present is “a distributive model, [the agencies] all club together, so the MHRA doesn’t need to build the capability” to review all the medicines that are submitted, he noted. “This is very cost effective.” But the challenge is that the UK will find it difficult to build the resources for a stand-alone system.
Some 80% of the MHRA’s income comes from industry fees, and “it is very clear that we would not be able to sustain the level of fees required to build up an authority for the review of medicines,” Thompson said. “So we have been talking about taking decisions from other stringent authorities which could still be the EMA and the [US] FDA, and then get the MHRA essentially to do a very small process to look at them and adopt them.”
Asked how much influence the UK might lose over EU regulatory standards as a result of Brexit and the relocation of the EMA from London to Amsterdam, the ABPI chief said that “if the outcome is that the MHRA is still involved in the EMA, which is the industry proposal, then I believe the quality of its capability and its expertise will still have huge influence, actually regardless of whether it has a vote or not.”
Votes at the EMA committees, he said, “tend to be taken by consensus, this is a scientific debate, it is more about being at the table than being able to influence the decision that is important, and I think everyone would benefit from the MHRA participating.”
Alternatively, the UK agency has said it will try to build alliances with other stringent regulatory authorities elsewhere world, but “in the short term, 75% of the value of medicines is in the US and the EU, and if you don’t participate in those two parts then you are inevitably diminished in terms of your influence.”
Generics And Non-Prescription Medicines
The question of how long the MHRA will be able to continue playing the role of rapporteur in centralized drug reviews – given that regulatory review times started now may extend beyond the Brexit date – is one that has come up before.
The impact will also be felt where the MHRA is the reference member state for drugs going through the mutual recognition and decentralized procedures – an issue that was raised at the hearing by two other witnesses, John Smith, chief executive of the Proprietary Association of Great Britain (representing the non-prescription drug sector), and Paul Fleming, technical director of the British Generic Manufacturers Association.
“A lot of companies, even though they don’t want to, are starting to think about using other regulatory agencies for their processes” – John Smith, PAGB
Looking at the non-prescription sector, Smith said the MHRA was “very pragmatic and forward thinking” in giving patients access to non-prescription medicines. However, his member companies are now saying that the advice coming out of Europe is that “if you have a process going beyond the date, you need to think very seriously about whether to use the MHRA,” because by the end of March 2019 the agency “will not be part of Europe,” Smith said. “So a lot of companies, even though they don’t want to, are starting to think about using other regulatory agencies for their processes.”
Asked what the lead times were for such decisions, Smith said “now”. Companies need to start taking decisions “very very soon”, he said. Firms, Smith said, were “trying to hang on to try and understand whether there is going to be some sort of guidance, either there is going to be a transition period or we are going to have some sort of statement from the government saying that there won’t be any divergence, but they need to start taking those decisions now, or at least by the first quarter [of 2018].”
Fleming agreed. Registering a generic medicine under the current system takes an average of 15 months, “so we are right on the decision point now.” The MHRA had been very good in terms of performance, and consistent in meeting the timelines, and “15 months start to finish has been something that the industry has been able to plan for over the last decade”, he said.
However, anything that brings risk factors into that equation raises the question of whether “people going to change their choices. Particularly for generics companies there is a large number of products involved – some of our bigger companies will have more than 500 products in their portfolio... the link between the regulatory process and what it means for when medicines become available and how companies have to sequence their planning, all of that is a very big part of the thinking and scenarios that companies are working to at the moment.”
Approval Applications, Clinical Trials
Witnesses also highlighted the possible impact of Brexit in terms of delayed access to new drugs and the UK as a site to conduct clinical trials.
Mark Hicken, managing director, UK & Ireland, for Johnson & Johnson, said that when multinational companies are taking decisions on where to make initial regulatory submissions, “usually you go to the largest markets, so the EMA and the US. If the UK were to be considered a separate market entirely, at less than 3% of the global potential, and if processes were different, it would slip down the priority list, so that is the worry. The bigger worry for patients in the UK is it would slow down access,” he declared
“If the UK were to be considered a separate market entirely, and if processes were different, it would slip down the priority list” – Mark Hicken, J&J
As for clinical trials, Thompson suggested that companies might shy away from the UK post-Brexit and even that data generated in the UK might not be accepted for EU approval applications.
Under the new Clinical Trials Regulation, companies will be able to make a single application to run a clinical trial across multiple EU countries. However, the regulation is not expected to come into effect until late 2019 and so it may not apply to the UK, meaning that companies may have to file separate applications for the EU and the UK.
“The issue before us is that if we are doing clinical trials, particularly towards the later stages of drug development, you end up needing so many patients that you do them in multiple centers,” Thompson said. “So if you are a company and you’re saying I need to have 8,000 patients in that trial and so I will need 40 centers or whatever to recruit those patients, if you have to go through two systems of approval it is quite possible you are going to say you know, I can’t be bothered to do that, actually I can do it through one, why would I take the extra cost, why would I take the extra complexity?”
Also, if there was not complete alignment on clinical trials, “it could be that the EU would say we’re not going to accept the results from the UK centers because they are not being governed by exactly the same legislation, and therefore those patients we will not take into account in a licensing decision in Europe,” Thompson suggested.
New Guidance For Companies
Separately, the EMA and the commission have published an updated Q&A document for pharmaceutical companies to help them prepare for Brexit, with new sections on different types of products such as generics, biosimilars and hybrid medicines. This will sit alongside the procedural guidance document the EMA issued last month. (Also see "EMA Explains How To Make Brexit-Related MA Changes, As Industry Bodies Urge Transition Period" - Pink Sheet, 28 Nov, 2017.)
From the editors of Scrip Regulatory Affairs.