If and when the United Kingdom leaves the European Union, the Medicines and Healthcare Products Regulatory Agency is poised to provide its own review structure for biosimilars.
During the SMi 10th Annual Biosimilars Conference, being held in London, United Kingdom, numerous speakers have noted that the United Kingdom has been a biosimilars success story. With high uptake of anti—tumor necrosis factor therapies and policies that drive biosimilar adoption, the United Kingdom has led among nations in the EU5 in its biosimilar initiatives. However, as uncertainty about the UK withdrawal from the European Union grows deeper, and with the current October 31 deadline for Brexit looming, there remain serious questions about the future of UK biosimilars.
During the second day of the SMi conference, Michel Mikhail, international regulatory affairs expert, moderated a discussion between Liz Pollitt, PhD, director at BioPharma CMC Regulatory Consultancy Services, and Anne Cook, PhD, biologicals quality assessor, UK Medicines and Healthcare Products Regulatory Agency (MHRA), on how Brexit could impact the future of biosimilars.
If and when the United Kingdom leaves the European Union, the MHRA is poised to provide its own review structure for biosimilars. First, to ensure that drugs that reach the United Kingdom via the European Union’s centralized marketing authorization route can continue to be provided to UK patients, all EU centrally authorized products will automatically be granted UK marketing authorizations on the date of the UK exit.
Additionally, according to UK guidance for the case of a no-deal Brexit, the MHRA will also offer new assessment procedures for new active substances and biosimilars that have received positive opinions from the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use. The MHRA will review applications for all such products within 67 days, and will thereafter provide a “rolling review” of new drugs and biosimilars that will allow companies to apply for authorization in stages throughout product development.
According to Cook, this speedier review process will also offer a reduced fee structure for targeted assessments of drugs that are already approved by the European Medicines Agency (EMA), and the rolling review period “will be a significant advantage” for biosimilar products because developers will have access to regulatory advice earlier than is available from the EMA. Being able to bring together a dossier on a truncated timeline could benefit biosimilar developers, as these robust packages could later be used as part of the EMA approval process.
In response to the moderator’s question about whether the MHRA will take a different approach to regulation than the EMA, Cook said that there exists an opportunity for the MHRA to improve on certain aspects of the biosimilar review process, but no changes are currently being planned. If updates to biosimilar regulation emerge at the EMA level, and if the United Kingdom does not take part in making those changes, the MHRA will “look at those and see if those are sensible,” though Cook said she sees no need to diverge from the European Union “unless Europe goes in a direction that we feel is not particularly useful.”
For Pollitt, however, the offer of a rolling review from the MHRA does not seem like a particularly attractive incentive for biosimilar developers to consider the UK market first. In the US context, she pointed out, feedback from the FDA is first given at the New Drug Application stage, but the EMA does not generate the same type of feedback until later in the regulatory process.
“In practice, we would only be creating the data that we need to get into a clinical study at that point,” which dilutes the value of early comments from the MHRA, she indicated. While the rolling review process does have some potential benefits, “it is not something that makes me think, ‘oh great, that’s something we’d want to use.’”
For Pollitt, while the fact that the United Kingdom will grant centrally authorized EU products marketing authorizations in the UK automatically on the day of Brexit is welcome, there remain challenges related to the time and costs that developers must put in to making updates to such items as packaging and leaflets for their drugs for the UK market. Such expenditures were not necessarily part companies’ plans, so there will be issues related to resources.
Pollitt raised the question of how to make the United Kingdom a more attractive venue for biosimilar development after Brexit, and asked Cook whether there could be changes to phase 3 clinical study requirements in the UK regulatory landscape.
Cook replied that updates to these requirements have been a topic of discussion at the European level, as well as the World Health Organization level, for some time. With more than 50 biosimilar products approved, there exists a good quantity of evidence to assess to see which kinds of studies were the most useful.
Pollitt added that there is “nothing in the clinical studies that couldn’t or wouldn’t have been identified by the analytical studies…whether they’re necessary for commercialization is something different. You can obtain that information a different way,” such as through real-world evidence.
Mikhail added that “there’s a type of relaxation of requirements in Europe” in terms of the kinds of data submitted to support biosimilarity. “If you have the so-called fingerprint-like similarity…then you have the structure—function similar and your in vitro package…you don’t need to conduct any more studies.”
While the matter of the potential to reduce or even waive phase 3 study requirements has been a hot topic in the biosimilars space in recent weeks, there are also more immediate challenges that the United Kingdom must face with respect to keeping its biosimilars market viable.
As Pollitt pointed out, one potential issue may be situations in which originator companies choose not to have their reference products licensed in the United Kingdom. While a biosimilar developer could have an EU-licensed biosimilar of such a medicine, that product could not be licensed in the UK market.
On this point, Cook allowed that “there’s work to be done,” and said that, given the complexities surrounding Brexit, at MHRA, “we’ve been generating policy as we’ve gone along.”