Vials of a Covid-19 vaccine move along a conveyor on the production line in India, 2021.

The United Kingdom plans to give the green light to some medicines on the basis of decisions made by other national regulators.Credit: Dhiraj Singh/Bloomberg via Getty

Critics of a plan by UK regulators to fast-track appraisals of new medicines that are already approved in other countries are sceptical about claims that it will boost life-science investment. They also warn that it could foster an over-reliance on approval processes in the United States and elsewhere.

UK chancellor Jeremy Hunt announced as part of his budget in March that the government was allocating £10 million (US$13.1 million) to assist the country’s Medicines and Healthcare Products Regulatory Agency (MHRA) in giving “near automatic sign-off” to drugs previously approved by other, trusted regulators. Hunt said that the new regulatory framework was part of the government’s plan to make use of “Brexit autonomy” to attract inward investment, boost UK life-sciences investment and give people quicker access to new drugs now that the country has left the European Union.

In May, the MHRA revealed further details of the plan, announcing that from early 2024, it will fast-track decisions on medicines that have already been approved by regulators in the United States, the European Union, Australia, Canada, Japan, Switzerland and Singapore. But some health-policy researchers are concerned that the model could open the door to medications that have not been properly assessed for safety and efficacy.

“The emphasis on speed in these proposals sends a signal to pharmaceutical companies that the United Kingdom is an attractive market to launch their products in,” says Huseyin Naci, who studies pharmaceutical regulation and health-policy evaluation at the London School of Economics and Political Science. “However, regulators need to delve properly into the data to evaluate the safety and benefits of new drugs. Medicines approved quickly under arbitrary deadlines have been shown to be more likely to trigger adverse safety events,” he says, and be subsequently withdrawn.

Alternative paths

Following the United Kingdom’s 2016 vote to leave the EU, some researchers warned that patient access to new drugs could be delayed or lost owing to the increased regulatory burden of applying for separate approvals. This might have made the United Kingdom a less desirable market for pharmaceutical companies. “Once companies have developed new products, they usually target the largest, most profitable markets,” says Naci. “The need to submit another application to another regulatory agency may be too burdensome for companies that want to maximize their profits as quickly as possible.” In 2022, the United States accounted for 43% of the global pharmaceutical market, Europe as a whole 22% and the United Kingdom 2.3%.

The MHRA became an independent national regulator at the start of 2021, following its withdrawal from the European Medicines Agency (EMA) in 2020. It launched assessment routes for marketing-authorization applications and joined collaborations with international, non-EU regulators with the aim of accelerating the regulatory review of new drugs through parallel and collaborative processes. Drug companies have, however, made significant use of the ‘reliance routes’ rules that allow them to apply for accelerated MHRA appraisals of medicines already approved by the European Commission in the EU and in Norway, Iceland and Liechtenstein.

This was evident in a 2022 study1 by a group led by Matthias Hofer, a health-policy researcher who specializes in drug regulation at Imperial College Business School and at a charity and consultancy called the Office of Health Economics, both based in London. In 2021, the MHRA approved 35 medicines, compared with 40 by the EMA and 52 by the US Food and Drug Administration (FDA), according to the study. The study also found that 68% of the MHRA’s authorizations during this year were based on previous European approvals. It’s not clear whether Brexit has driven a decline in drug-approval applications, says Hofer, owing to the study’s short time frame and the fact that the MHRA has not released information on when applications are submitted.

Pharmaceutical companies can seek marketing authorizations for drugs through several regulatory routes, depending on factors such as the type of condition a drug is designed to treat and the quality of evidence to support its use. These routes include those for rare conditions and unmet medical needs, accelerated pathways and those conditional on further evidence being provided. The Innovative Licensing and Access Pathway, launched by the MHRA in January 2021, is designed to speed up the development and review of medicines by giving both commercial and non-commercial developers regulatory support, from preclinical development to marketing authorization.

The European reliance route for UK drug appraisals will close at the end of this year, and will be replaced with international recognition routes. “Through this new dual approach, we will contribute to the United Kingdom’s ambition to be a global science superpower,” said June Raine, chief executive of MHRA in London, in May.

Crucial juncture

The UK life-sciences sector is worth more than £94 billion to the country’s economy, and employs some 280,000 people. In 2019, the nation spent £4.8 billion on pharmaceutical research and development (R&D), and in a typical year its investments in the sector account for around one-fifth of total industrial spending on R&D. In biological sciences, the United Kingdom was ranked third in the world for output in Nature Index journals in 2022 — behind the United States and China, but ahead of Germany (a country it trails overall in the Nature Index).

However, when it comes to commercial clinical trials, a key part of drug R&D, the United Kingdom is doing less well. It dropped from fourth to tenth in a global list of countries in which phase III commercial trials began between 2017 and 2021, according to an October 2022 report by the Association of the British Pharmaceutical Industry. The number of clinical trials initiated in the United Kingdom dropped by 41% during the same period.

A government-commissioned review, published in May, set a target of doubling the number of people participating in clinical trials within two years and doubling it again by 2027. Led by former government minister James O’Shaughnessy, the report called for regulatory burdens for starting clinical trials to be reduced, and for physicians to be offered incentives to recruit people to take part in trials.

Some health researchers say that Brexit has played a key part in the decline of commercial clinical-trial activity in the United Kingdom. Mark Lythgoe, a pharmacist who studies oncology at Imperial College London, points out that UK researchers no longer have access to central databases of information on European clinical trials. Furthermore, he notes, participation of UK groups in European trials has been restricted by the country’s divergence from EU clinical-trial infrastructure and policies. “It means that a lot of UK academics are struggling to join pan-European clinical trial groups,” he says. “The United Kingdom is also falling behind in leading and participating in the pivotal cancer trials that are generally used as part of global licensing applications.” This role was further hit in June by the announcement that the National Cancer Research Institute in London, which helped to coordinate clinical trials for cancer drugs, was closing after 22 years.

Regulatory reliance

Hofer says that the MHRA’s regulatory approach is unlikely to provide the significant boost to the life-sciences industry that politicians such as Hunt are hoping for. “Multiple factors can play a role when the pharmaceutical industry determines where to invest, including the regulatory environment and other aspects like R&D infrastructure, access to skilled labour and the tax environment,” he says. “There is no evidence to suggest that the proposed, more streamlined and harmonized MHRA medicines-approval system will directly lead to higher R&D investment into the United Kingdom.”

Other health-policy researchers are concerned that the recognition routes for the quicker approval of drugs will mean less scrutiny and greater reliance on the FDA, for example.

“Drugs can be approved in the United States through an accelerated approval process when the data doesn’t prove clinical benefit but is strongly suggestive of it,” says Lythgoe. “Some of these are subsequently withdrawn if it is found that they don’t work, or because of concerns about adverse effects, so the idea of essentially outsourcing these decisions to regulators like the FDA is concerning. The United Kingdom needs to ensure that it has the necessary framework to rapidly withdraw drugs if they are found not to have true patient benefit.”

Naci agreed that it is a mistake for the MHRA to follow the FDA’s lead. “If the plan gives almost automatic sign-off to drugs that have been approved by other regulatory agencies, the MHRA will become subject to the intense industry lobbying seen in the United States that has in the past led to some really controversial decisions.”

The MHRA denies that its new approval processes would weaken its independence or lower its standards of scrutiny. “The MHRA will retain sovereignty and will be able to reject individual ‘recognition route’ applications from partner countries if it does not consider the evidence provided to be strong enough to have their medical product licensed in the United Kingdom,” says Glenn Wells, who is chief partnerships officer at the MHRA.

Naci acknowledges that the MHRA’s regulatory model could encourage companies to launch products in the United Kingdom, but argues that this should not come at the expense of safety or efficacy. “The ideas that any new clinical trial is good, any new product is good and that the numbers of new drugs coming on to the market is the only metric of success, need to be questioned,” he said. “What we should really be looking at is the number of new products that are coming on the market that are adding new benefits to patients.”