At the end of the Brexit transition period, the UK will be charting its own course through the often choppy seas of medicines regulation. While it plans to retain the existing EU rules that have been transposed into domestic legislation, it also wants the freedom to tailor its regulations in areas like clinical trials, advanced therapies and product labeling.
The UK government has outlined its vision for creating a “world-leading, dynamic system of medicines regulation” once the UK fully leaves the EU at the end of the Brexit transition period on 31 December.
Among the aspirations are more streamlined procedures for clinical trials, advanced therapies and personalized medicines, a domestic medicines track-and-trace system similar to that of the EU, and digital platforms for companies to update their product information.
The government claims the changes will “cement our ability to enable early access to cutting edge technologies and break new ground in complex clinical trials” and enable the Medicines and Healthcare products Regulatory Agency to “continue its role as a forward-thinking regulator.”
Businesses, including medicines and medical device manufacturers, as well as the academic and research sectors, will all benefit from “operating within a dynamic, flexible, regulatory system with the ability to adjust for innovations or market developments.”
The proposals take the form of the Medicines and Medical Devices Bill 2020, which is intended to provide continuity in medicine and device legislation once the UK is no longer obliged to follow EU rules, by allowing it to amend and update domestic legislation to reflect developments and innovations in the sector.
The bill was presented to the House of Commons and given its first reading (a formal part of the legislative process with no debate) on 13 February. It will now go for its second reading, scheduled for 2 March, where the overall principles of the bill will be considered before it passes to the committee stage.
In an impact assessment accompanying the bill, the government says that the UK life sciences sector currently has a “sophisticated, proportionate and responsive medicines regulation system” that ensures that clinical trials and the manufacturing of medicines meet quality and safety standards. “It thereby safeguards the supply chain and provides manufacturers with a stable market to sell to”, which “in turn reduces business risks and costs.”
The UK BioIndustry Association said the bill was “an enabling vehicle, designed to introduce targeted delegated powers in the fields of medicines, clinical trials and medical devices to update the existing regulatory frameworks in line with international and scientific standards following the UK exit from the EU, as well as to consolidate the enforcement provisions for medical devices.”
The BIA said it would be monitoring the bill as it progresses through parliament “to ensure that it enables faster patient access to new, innovative medicines while supporting the growth of the UK’s world-leading life sciences sector.”
At present, the medicines and medical products sectors are regulated by EU legislation that in the UK has been transposed in the form of the Human Medicines Regulations 2012, the Medicines for Human Use (Clinical Trials) Regulations 2004, the Medical Devices Regulations 2002, and the Veterinary Medicines Regulations 2013.
When the Brexit transition period ends, the EU Withdrawal Act will preserve these regulations as “retained EU law”, but it will also take away the government’s power to amend the medicines regulations using secondary legislation such as statutory instruments, meaning that any changes, even minor details, would require primary legislation such as an Act of Parliament.
The loss of this power, the government says, would “prevent the maintenance of a dynamic, fit for the future regulatory system capable of adjusting for future innovation, with expected negative impacts on patient outcomes, population health and the UK’s competitiveness in the food and life sciences sectors.”
The bill would restore this power so that the government can easily make changes to the regulations as needed. This, it says, would allow the UK to keep up with “developments and innovations” and “cement our ability to enable early access to cutting edge technologies and break new ground in complex clinical trials.”
Changes could include, for example, amending the requirements for new drug marketing, manufacturing and wholesaling authorizations, the import of active pharmaceutical ingredients, and the labeling and packaging of human medicines.
Reflecting its recent statements about the need for flexibility in regulations to improve its ability to strike trade deals with other countries such as the US, the government says that being able to change the regulations using secondary legislation could allow the UK’s regulations to “accommodate world best practice and standards, ensuring we are competitive in our pursuit of free trade agreements.”
The bill proposes a number of specific changes, including what the government calls “innovative regulation of novel therapies, precision medicines and complex medical devices” via a “distributed manufacturing model” for products for use either within or outside clinical trials.
It says that innovation in healthcare is moving to models such as personalized medicines that are manufactured close to the patient (in a clinic or hospital), such as cancer vaccines using the patient’s own tissue as a starting material, and advanced therapies with an ultra-short shelf life that are produced in the operating theater for immediate administration to the patient.
“As clinical uptake increases, personalized/short life medicines require ‘scale out’ to many (potentially hundreds) of clinic/hospital/ theater-based manufacturing facilities,” the impact assessment says. “With these products it would not be feasible to require a traditional manufacturing licence and inspections prior to the release of the product for each clinic/hospital/theater.”
In order to maintain a regulatory system that is “fit for purpose and in support of medical innovations,” steps would be taken to facilitate a “distributed manufacturing model,” initially for products manufactured for use in clinical trials. This would allow the holder of a manufacturing licence to use a centralized control center to supervise each distributed manufacturing site’s quality system for specific products.
The regulations could be amended to define a central “control site” where a manufacturing authorization and a qualified person would be required, while exempting the distributed manufacturing sites from needing their own manufacturing authorization and QP. Medicines manufactured at the point of care would be regarded as “prepared industrially or manufactured by a method involving an industrial process (unless regarded to be exempt).”
Such a move, the government says, would offer a “modernized regulatory approach tailored to this flow of new and innovative products” and “place the NHS at the forefront of modern medicine – manufacturing specialist medicinal treatments at the patient’s bedside.”
The government also foresees benefits in the area of clinical trials, where there is “often continuous change in adding new trial sites and removing others as trial subject recruitment changes.” Unnecessary time and cost burdens caused by having to apply for manufacturing license variations could be avoided, helping to “support the UK to maintain its competitiveness in the clinical trials sector.”
The government plans to make some other post-Brexit changes to the clinical trial rules. As a third country outside the EU, the UK will not be subject to the EU Clinical Trials Regulation, which is expected to take effect around the beginning of 2022 and so will not form part of retained EU law. (Also see “Yet More Delay For EU Clinical Trial Regulation” – Pink Sheet, 24 Dec, 2019.)
The bill offers a mechanism to update the current trials framework, for example by removing “unnecessary and duplicative regulatory burdens for clinical trials, particularly the lowest-risk trials, and so make it easier for researchers and companies to rapidly trial new medicines while also ensuring we are consistent with global standards and best practice.”
The government plans to introduce its own medicines track and trace system if it does not remain part of the EU’s European Medicines Verification System, which was launched in February last year as required under the EU Falsified Medicines Directive. The EMVS involves a “unique identifier” on each prescription drug pack, and a system of scanners to authenticate packs when entering and “checking out” of the system.
The UK will be part of this system until the transition period ends, but the country’s participation beyond then is in doubt and would need to be discussed as part of the negotiations on the future relationship between the UK and the EU. (Also see “Europe’s Medicines Verification System Prepares To Go Live” – Pink Sheet, 7 Feb, 2019.)
The UK could also change the product labeling regulations. The current rules require a hard-copy patient information leaflet to be included with every original pack. “Given the increasing appetite for digital information access, we could consider whether hard copy leaflets continue to be the most appropriate vehicle for delivering this information to patients,” the government says.
The bill would allow the government to require manufacturers to provide and maintain up-to-date statutory information about certain medicines on a variety of digital platforms “and for all packs dispensed to signpost these resources.”
This might apply to a specific medicine only, a class of medicines “or (at least theoretically) all medicines. This is necessary as we cannot foresee what medicines will be available in the future, nor whether information requirements might change for existing treatments if side-effects arise.”
Finally, online pharmacies would be subject to a national registration scheme. Online sellers currently must register with the national authority, comply with certain standards and display a standard EU logo. “However, this logo is copyrighted by the European Commission and participation in the scheme is dependent upon the outcome of the negotiations on the future relationship”, the government points out. The UK would require sellers to register with the MHRA and display a common logo on their websites; it could also decide to have additional safeguards or conditions as part of the scheme.