Sue Pearson Ph.D. Freelance Writer GEN

Making the Nation a One-Stop Regulatory Engine for Innovation

“The U.K. remains a fantastic place for innovation, with broad academic, regulatory, and clinical expertise which works at a national and global level and that won’t go away post-Brexit,” said Ian Hudson, M.D., CEO of the Medicines and Healthcare Products Regulatory Agency (MHRA), at the recent annual BIA/MHRA Conference.

To support these assertions, Dr. Hudson opened the conference with an introduction to how the MHRA is supporting innovation in the U.K. He discussed how the MHRA is structured of three centers: The Clinical Practice Research Datalink (CPRD), National Institute for Biological Standards and Control (NIBSC), and the MHRA regulatory center; each with distinct roles.

Dr. Hudson stated, “The CRPD is an NHS observational data and interventional research service which has access to anonymized data from millions of patients and is a rich source of information for observational research studies clinical trials. NIBSC is in charge of standardization and control of biological medicines and supplies over 90% of the world’s international biological standards. The MHRA is involved in successful regulation of many medicines, medical devices, blood, and blood products every year.”

According to Dr. Hudson, one of the MHRA’s main themes in its five-year corporate plan for 2013–2018 is “bringing innovation safely to market.” Dr. Hudson detailed that to achieve this ambition, the MHRA has opened an innovation office and launched the U.K. Early Access to Medicines Scheme (EAMS) to provide access, on an unlicensed or off-label basis, to medicines for serious conditions without adequate treatment options.

Dr. Hudson said, “Since opening, the Innovation office has responded to 570 enquiries, held over 120 regulatory meetings, and answered 60 ‘one-stop-shop’ RASRM (Regulatory Advice Service for Regenerative Medicine) enquiries. The EAMS has had 52 Promising Innovative Medicine (PIM) designations—an early indication that a product may be a possible candidate for EAMS—and the MHRA has issued 19 benefit–risk scientific opinions on specific products to facilitating speedier patient access in areas of unmet need.”

According to Dr. Hudson, to ensure the MHRA continues to work with regulators throughout the world, it is also an active member (and current chair) of the International Coalition of Medicines Regulatory Authorities (ICMRA), which is a voluntary, leadership body of many of the major medicines regulatory authorities from around the world who work together to address global medicine regulatory and safety challenges. Dr. Hudson concludes, “The MHRA is working in a rapidly changing environment in the U.K., which means it is vital that we continue to support innovation.”





Opportunities

One area of innovation in which the U.K. is trying to gain a strong foothold is advanced therapy medicinal products (ATMPs). Christian Schneider, M.D., director of the NIBSC, cited several examples of where the Institute is developing standards and techniques to support cell and gene therapy, such as a lentiviral vector standard. He explains, “The natural presence of a homologous sequence is shared by all three generations of lentiviral vectors, so that the lentiviral vector standard will stand test of time and ensure that a negative test result must be ‘truly’ negative and insertional mutagenesis events can be quantified. This helps increase regulatory certainty and may reduce regulatory burden.”

According to Dr. Schneider, post-Brexit the U.K. should be a “one-stop regulatory engine for innovation” because it is moving toward an ATMP infrastructure rather than just a network. He explains, “The U.K. has a strong life sciences industry, world-class academic centers, and an embedded, strong regulator that can provide specialist expertise for assessment and advice in this field, and we should continue leveraging these things internationally.”

In terms of clinical studies, Dr. Martyn Ward, MBBS, group manager, licensing, at the MHRA presented data to show that Brexit has not yet had an effect. Dr. Ward explains, “Clinical trial application numbers have remained steady at around 1000 per year, with the trend in the U.K. for fewer Phase I and IV and an increase in Phase II and III trial applications over the last decade. Additionally, in 2017 we saw an increase in first-in-human trials and in terms of gene and cell therapy trials, the U.K. alongside Spain are the most popular European countries for performing this type of clinical study.”

According to Dr. Ward, the MHRA is preparing for all scenarios in relation to clinical trials post-Brexit. For example, the U.K. will align with the EU’s new Clinical Trial Regulations (CTRs) and is committed to providing a new U.K. database and portal if no deal is agreed with the EU. Dr. Ward states, “The U.K. has contributed significantly to the development of the new CTRs and the U.K. Government has committed it will align with them as far as possible. Post-Brexit, if outside the EU Network, the U.K. could have a more streamlined clinical trial application process with shorter timelines compared to the EU because the U.K. does not need the time for collaborating within the network. The MHRA has taken steps to ensure there will be no interruption to U.K. regulatory procedures so that trials will continue whatever the outcome of the Brexit negotiations.”

To ensure patients in the U.K. can continue to access innovative therapies, Professor Sir Michael Rawlins, M.D., chair of the MHRA, detailed the work of the Accelerated Access Collaborative, which was set up in 2018 in response to the Accelerated Access Review. According to Rawlins the AAC will scan for new breakthrough products and streamline the development pathway, as well as supporting adoption of products via the 15 Academic Health Science Networks across NHS England. Dr. Rawlins concludes, “The MHRA will continue to work with industry, academia, and patient groups to facilitate patient access to innovative treatments and therapies.”





Challenges

Alan Morrison, vice president, international regulatory affairs, at Merck & Co., delivered a more sobering message about the potential effects of Brexit on the U.K. life sciences industry and the patients it serves. He states, “45 million patient packs [treatment-specified amount of medication along with accompanying documentation for the patient] are supplied by the U.K. to EU 27/EEA (European Economic Area) every month, and 37 million patient packs are supplied by EU 27/EEA to the U.K. every month, without a Brexit deal, it’s possible that patients will experience a supply problem.”

Morrison then detailed a range of challenges that could occur in the case of a “no-deal” Brexit trade scenario in terms of manufacturing and supply, clinical trials, and regulations: “Over 60% of EFPIA (European Federation of Pharmaceutical Industries and Associations) members have batch testing done in the U.K., without a deal there will be no mutual GMP recognition or access to NIBSC control. This could lead to more lab testing with products having to be released by a U.K. and an EU Qualified Person (QP) plus additional import testing. If the work is transferred to the EU, then technical transfer could take up to 24 months.”

Morrison continued: “Around 70% of Investigational Medicinal Products (IMPs) in ongoing EU clinical trials are released from the U.K. and there will be an impact on supply if these have to be released by a U.K. and an EU QP. Additionally, the U.K. is the Reference Member State (RMS) for around 3400 Mutual Recognition Procedure (MRP) or Decentralized Procedure (DCP) products and all of this would have to be transferred to an EU RMS.”

According to Morrison, pharmaceutical companies have been assiduous in their business continuity planning for Brexit. This includes the commitment of significant resources across multiple global functions to Brexit implementation task forces to deal with the outcome of a range of Brexit deal scenarios including the potential for a “no deal” as there is currently no clarity on whether a deal will be agreed upon.

Mr. Morrison added, “Clearly a transition period to implement changes is going to be key to ensuring that companies, national competent authorities, and the EMA can deliver the necessary changes so that patients can continue to access their medicines.” He warns, “If the U.K. ends up in a ‘no Brexit deal’ situation with the EU, then patients in the U.K. will end up being deprioritized for access to future new medicinal products.”



























































































































































