The Life Sciences Law Review: United Kingdom
This chapter summarises the UK regimes governing medicines and medical devices. The United Kingdom has left the European Union (EU) (Brexit) and the post-Brexit transitional period has come to an end, meaning that the UK is now no longer bound by any EU pharmaceutical or medical device laws. The one exception is Northern Ireland. At the time of writing, the Northern Ireland Protocol to the Withdrawal Agreement between EU and the UK applies and it aims to avoid a hard border between Northern Ireland and Ireland by keeping Northern Ireland within the EU single market for goods. Goods flow to and from Northern Ireland, Ireland and the rest of the EU as they did while the UK was a member of the EU, without customs checks or tariffs. To achieve this, EU pharmaceutical and medical laws continue to apply to and in Northern Ireland, while Great Britain (the UK minus Northern Ireland) will be able to develop its own laws for these sectors. However, there are ongoing discussions between the UK and EU about the protocol (discussed further below).
The starting point for that legislative process was the European Union (Withdrawal) Act 2018 (the EWA 2018), which enabled the transposition of directly applicable, already-existing EU law into UK law at the point of Brexit. This included much of the EU's pharmaceutical and medical device laws, so we will not repeat much of the substantive content of the European Union chapter. Rather, we focus on unique features of the UK, Great Britain and Northern Ireland regimes, including steps that the UK has taken to develop its own regulations. While the chapter should be read in conjunction with the European Union chapter, the regulatory position in the United Kingdom, or at least Great Britain, is likely to change significantly in the future.
Medicines for human use are regulated primarily by the Human Medicines Regulations 2012 (the Medicines Regulations).2 The Medicines Regulations implemented Directive 2001/83/EC3 and most other EU medicines laws into UK law. Clinical trials are regulated primarily under the Medicines for Human Use (Clinical Trials) Regulations 2004.
Medical devices are regulated by the Medical Device Regulations,4 which implement the three EU Medical Devices Directives5 into UK law. Importantly, the UK decided it would not give effect to Regulation (EU) 2017/7456 on Medical Devices, and Regulation (EU) 2017/7467 on In Vitro Diagnostic Medical Devices, although the Regulations will apply in Northern Ireland.
The Medicines and Healthcare Products Regulatory Agency (MHRA), an executive agency of the Department of Health and Social Care, is the United Kingdom's national competent and enforcement authority for the regulation of both medicinal products and medical devices. However, the 'licensing authority' is responsible for the granting, renewal, variation, suspension and revocation of licences, authorisations, certificates and registrations under the Medicines Regulations. The licensing authority comprises either or both of the Secretary of State for Health and the Minister for Health, Social Services and Public Safety, acting on the advice of the MHRA. Likewise, the Secretary of State exercises certain powers under the Medical Devices Regulations. The 'enforcement authority' comprising relevant ministers is responsible for authorising inspectors and for bringing enforcement actions.
The regulatory regime
The MHRA has primary responsibility for determining whether borderline products are medicinal products or medical devices. The MHRA's Medicines Borderline Section considers each product on its merits and any information that may have a bearing on the product's status.
The Borderline Section provides informal, written advice on classification in response to specific enquiries about potential borderline issues. However, it will also exercise its enforcement powers following complaints about a particular product or based on its review of a product.
ii Non-clinical studies
The Animals (Scientific Procedures) Act 19868 permits research involving animals only in premises licensed by the Home Office, by appropriately qualified staff and in accordance with procedures designed to minimise animal pain and suffering.
The Good Laboratory Practice Regulations 19999 require that all animal studies be conducted in accordance with sound standards of good laboratory practice. These standards reflect the Organisation for Economic Co-operation and Development requirements.
iii Clinical trials
Clinical trials of medicines for human use are regulated under the Medicines for Human Use (Clinical Trials) Regulations 2004 (the Clinical Trial Regulations). Clinical trials of medicinal products in humans are generally only permitted if the MHRA has granted a clinical trial authorisation (CTA) and an ethics committee has issued a favourable opinion. A CTA is not required for 'non-interventional' trials, but the definition of a non-interventional trial is very narrow. It covers only trials involving approved medicines used on-label where there are no changes to routine medical care, including prescribing decisions or additional monitoring or information-gathering procedures.
Non-UK sponsors of clinical trials in the UK must designate a UK legal representative. All investigational medicinal products (IMPs) must have been manufactured or imported by the holder of a manufacturer's authorisation in the UK, unless they are sourced from a jurisdiction on the 'approved country for import list'. The list initially includes all EU and European Economic Area (EEA) countries. In such cases, a UK Manufacturing and Import Authorisation (MIA(IMP)) holder must put in place a system overseen by a Qualified Person (QP) to check these IMPs have been certified by a QP in a listed country, before release to trial sites.
Sponsors must submit reports of suspected unexpected serious adverse reactions relevant to a UK trial to the MHRA and the relevant research ethics committee. There is also a requirement to submit annual safety reports.
The Clinical Trial Regulations require sponsors to provide adequate insurance or indemnity to cover liabilities that may arise in relation to the clinical trial. The MHRA expects that a sponsor's insurance policy or indemnity will reflect the form recommended by the Association of the British Pharmaceutical Industry (ABPI) Clinical Trial Compensation Guidelines. The ABPI has also published specific insurance and compensation guidelines for Phase I clinical trials.
Clinical investigations of medical devices are governed by the Medical Devices Regulations. In addition to obtaining research ethics committee approval, the manufacturer must notify the MHRA prior to the conduct of a clinical investigation involving a medical device without a UK conformity assessment (UKCA) or CE mark.
There is a different process for performance evaluation of an in vitro diagnostic medical device (IVD) without a UKCA or CE mark. Manufacturers must draw up a declaration and follow the procedure set out in Annex VIII of the IVD Directive 98/79/EC and must also register details of the IVD for performance evaluation with the MHRA.
Manufacturers must report serious adverse events involving a device under clinical investigation to the MHRA. The MHRA requires manufacturers to provide insurance for subjects in clinical investigations of medical devices.
iv Named-patient and compassionate-use procedures
The Medicines Regulations allow the supply of unlicensed medicines in response to a bona fide unsolicited request by a healthcare professional to meet the unmet clinical needs of an individual patient. Medicinal products supplied under the named-patient exemption are known as 'specials'. A special may not be advertised (although price lists may be made available). The responsibility for patient safety remains with the prescribing clinician.
If a special is manufactured in the United Kingdom, the manufacturer must hold a manufacturer's (specials) licence granted by the MHRA. Importers of specials must hold the appropriate wholesale dealer's or manufacturer's authorisation. In addition, importers must notify the MHRA 28 days prior to importing a special.
The MHRA's Early Access to Medicines Scheme (EAMS) provides another exemption to the requirement for a medicinal product to have a marketing authorisation prior to being placed on the market. The EAMS has been adopted to enable patients with 'life-threatening or seriously debilitating conditions' to have early access to medicines that have yet to receive a marketing authorisation. The process for joining the scheme involves a two-stage evaluation by the MHRA: step I is the promising innovative medicine (PIM) designation, and step II is the EAMS scientific opinion. For medicines to qualify for the EAMS, they must meet the following criteria:
- the product is needed to treat a life-threatening or seriously debilitating condition, and there is a high unmet need;
- the medicinal product is likely to offer significant advantages over methods currently used in the United Kingdom;
- the potential benefits of the medicinal product outweigh the adverse effects; and
- the applicant is able to supply the product and to manufacture it to a consistent quality standard of good manufacturing practice (GMP).
The Medical Devices Regulations permit the supply of custom-made medical devices that meet the essential requirements but have not been CE-marked or UKCA marked, and also devices that do not meet the essential requirements, provided that the MHRA authorises their use.
The use of an individual non-complying medical device, for a single named patient, is permitted only in exceptional circumstances; for example, where no alternative CE-marked devices are available or where it has been demonstrated that the morbidity or mortality of patients is significantly reduced with the use of the device in question as compared to those using alternative available treatment. The MHRA requires that an application be made for each patient, which includes information from the manufacturer and relevant clinician.
v Pre-market clearance
The Medicines Regulations requires that a medicinal product has a marketing authorisation prior to being placed on the market. It is an offence for any person to sell or supply, or offer to sell or supply, an unauthorised medicinal product or a medicinal product otherwise than in accordance with the terms of a marketing authorisation.
The UK now has three forms of national marketing authorisations. UKMA(UK) is in force in the entire United Kingdom, UKMA(GB) is in force in Great Britain only and UKMA(NI) is in force in Northern Ireland only. UK marketing authorisations for Great Britain are granted by the MHRA under national procedures as they can no longer participate in EU mutual recognition procedures or decentralised procedures. Centralised marketing authorisations granted by the European Commission no longer apply in Great Britain but, unless the marketing authorisation holder opted out, all existing centralised marketing authorisations were converted into UKMA(GB)s on 1 January 2021.
However, at the time of writing, pursuant to the Northern Ireland Protocol, existing and future centralised marketing authorisations continue to apply in Northern Ireland. Also, Northern Ireland can continue to be included in EU mutual recognition procedures or decentralised procedures as a Concerned Member State.
The EU chapter summarises the conformity assessment and CE-marking procedures for medical devices. Because there is little regulatory pre-market review and approval of medical devices (with the exception of a medicines regulator's review of devices incorporating medicinal products and blood products), the MHRA has no involvement in the process leading up to CE marking.
Following Brexit, the UK has decided not to implement either the EU Medical Devices Regulation or its IVD equivalent. In the short term at least, the UK will align its medical devices regime with the current EU devices directives (although as the time of writing the MHRA is reviewing responses to its consultation on proposed changes to the medical devices regulatory framework). Until 2023, it will allow CE-marked devices to be placed on the market in the UK but, from 2023, medical devices for the Great Britain market must bear the UKCA mark. Post-Brexit, all medical devices and IVDs placed on the market in the UK must be registered with the MHRA, although there are grace periods for manufacturers of those classes of devices that were not required to be registered under the previous regulations.
vi Regulatory incentives
The Medicine Regulations implement the EU periods of eight years' regulatory data exclusivity (during which generic applicants cannot file) followed by two years' market exclusivity (during which regulators may review generic applications, but generic manufacturers cannot launch).
The UK will continue to offer orphan exclusivity in accordance with EU standards, but applicants will submit applications to the MHRA and timing of exclusivity protection will be calculated from the product's first approval in the UK. Similarly, companies must agree paediatric investigation plans (PIPs) with the MHRA post-Brexit and will benefit from rewards equivalent to those under EU law (although there is added complexity as the territorial scope of the supplementary patent certificate and marketing authorisations may vary).
In the United Kingdom, the Intellectual Property Office is responsible for granting supplementary patent certificates for medicinal products that meet the criteria under Regulation (EC) No. 469/2009.10
UK legislation does not provide specific regulatory exclusivity periods for medical devices. A device may be protected by a UK patent if it satisfies the requirements for patentability under the Patents Act 1977.11 A UK patent is granted initially for four years and is renewable annually thereafter up to a maximum of 20 years from the filing date of the patent application.
vii Post-approval controls
The United Kingdom's post-approval controls over marketing authorisation holders for medicines and manufacturers of medical devices currently closely mirror the EU requirements. However, reports and notifications are exclusively to the MHRA, post-Brexit.
Transfer of marketing authorisations for medicines
Marketing authorisation holders may apply to the MHRA to 'transfer' ownership of their marketing authorisations to third parties. If satisfied that the recipient is suitable to hold the approval, the MHRA will grant the transferee a new marketing authorisation. It will usually also allow the original authorisation to remain in force for a transitional period. This avoids interruptions in supply by allowing a product in the name of the original authorisation holder to be placed on the market until the new product is widely available.
Revocation, suspension or variation of marketing authorisations
The licensing authority, acting through the MHRA, has the power to revoke, suspend or vary a UK marketing authorisation. Companies that are unhappy with the proposal have the right to appeal to the appropriate committee, then to an independent review panel in accordance with Schedule 5 of the Medicines Regulations.
viii Manufacturing controls
The substantive requirements governing the manufacture of medicinal products, including the need for a manufacturing or import authorisation, a qualified person and compliance with GMP, are discussed in the European Union chapter.
The MHRA regulates pharmaceutical manufacturing and import operations within the United Kingdom, although the licensing authority actually grants, suspends and revokes manufacturing authorisations. The MHRA will conduct inspections of manufacturing facilities before authorisation and periodically thereafter.
Post-Brexit, entities with a UK wholesale dealer's licence can import medicines into Great Britain from a country on the 'approved country for import' list (which currently includes all EEA Member States) if the entity appoints a Responsible Person (import) and this person confirms (1) the required QP certification has taken place and, if applicable, (2) the required independent batch release certificate is available for biological products. Medicinal products imported from countries not on the approved country must be imported by the holder of a manufacturers import authorisation (MIA) and batch released for the Great Britain market by a UK QP. The UK has stated it will review its acceptance of batch testing done in EEA countries before 31 December 2022 and a two year notice period will be given in case of changes. However, at the time of writing, products entering Northern Ireland will need to be batch released by a manufacturer in the EEA. Therefore, entities that were previously a medicine retailer/wholesaler that obtains medicines from Great Britain would now need to be authorised as an importer (although the European Union did provide a limited transition period for products being imported into Northern Ireland from Great Britain).
ix Advertising and promotion
The Medicines Regulations implement the EU advertising rules into UK law. These include the general requirements that advertisements should not be misleading, that they should be substantiated and that they should be accompanied by appropriate prescribing information. There is also a prohibition on pre-approval or off-label promotion of medicines, advertisements of prescription-only medicines to the general public, and illegal inducements to prescribe. Guidance from the MHRA, called the Blue Guide on Advertising and Promotion of Medicines in the UK (the Blue Guide), supplements the Regulations and is intended to provide additional clarification on the interpretation and application of the law. The MHRA is the statutory enforcement body for these rules and requires pre-vetting of advertising material in some circumstances; for example, new active substances granted marketing authorisations.
The statutory scheme is supported by a long-standing system of self-regulation based on the ABPI Code of Practice for the Pharmaceutical Industry (the ABPI Code). The ABPI Code is enforced by a self-regulatory body called the Prescription Medicines Code of Practice Authority (PMCPA), which adjudicates complaints by competitor companies and individuals, but can also bring proceedings itself. The ABPI Code underwent a major overhaul in 2021 and is now more closely aligned with the European Federation of Pharmaceutical Industries and Associations Code of Practice (the EFPIA Code).
The ABPI Code governs the advertising of prescription-only medicines to health professionals, relevant administrative staff and to the general public. It only applies to companies that are members of the ABPI or that have formally agreed to abide by the ABPI Code. The success of this self-regulatory scheme has meant that the MHRA has not needed to exercise its statutory enforcement powers against legitimate pharmaceutical companies for nearly 30 years.
The provisions of the ABPI Code are consistent with the Medicines Regulations and in some instances more stringent. For example, under the ABPI Code, promotional material must not be issued unless its final form has been certified on behalf of the company by a person that is a registered medical practitioner or a UK-registered pharmacist. It also significantly limits companies' ability to provide promotional aids and seeks to regulate certain company interactions with the National Health Service (NHS).
The United Kingdom has no specific device advertising legislation. Medical device advertising is subject to general advertising rules, requiring that advertisements be substantiated, factual, balanced and not misleading.
The Association of British Healthcare Industries (ABHI) has incorporated advertising guidelines into its Code of Business Practice (the ABHI Code). The provisions of the ABHI Code only apply to ABHI members and companies that have formally agreed to abide by the ABHI Code. There is a complaints procedure, but at the time of going to press, the Complaints Adjudication Panel has yet to hear a complaint.
x Distributors and wholesalers
Distributors of medicinal products must hold a wholesale dealer's licence and must operate appropriate facilities and staff under the supervision of an appropriately qualified responsible person. They must comply with good distribution practices (GDP) and maintain appropriate batch records.
The licensing authority, acting through the MHRA, is responsible for issuing, suspending and revoking wholesale dealers' licences in the United Kingdom. The MHRA will conduct inspections prior to the grant of such a licence and then periodically thereafter.
The Medicines Regulations also regulate 'brokers', meaning persons who engage in activities in relation to the sale or purchase of medicinal products, except for wholesale distribution, that do not include physical handling and that consist of negotiating independently and on behalf of another legal or natural person. UK-based brokers must comply with GDP and must be registered with the MHRA.
The United Kingdom currently has no specific rules governing the distribution or wholesale of medical devices and the UK has indicated that it does not currently intend to implement the rules governing distributors and other economic operators in device supply chains under the EU Medical Devices Regulation (EU) 2017/745 and In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746. However, as these Regulations apply in Northern Ireland it should be noted that those acting as retailers/distributors in Northern Ireland and purchasing devices from Great Britain will now be considered as importers.
xi Classification of products
The Medicines Regulations presuppose that new medicinal products are generally restricted to use under medical supervision and made available only on prescription. There is also scope for imposing additional restrictions, such as requiring that certain products are prescribed only by specialists, or in hospitals. Non-prescription status is appropriate only for products with an appropriate level of safety and where self-diagnosis and treatment is appropriate without a healthcare professional's intervention or supervision.
There are two classes of non-prescription or over-the-counter drugs in the United Kingdom. Consumers must obtain pharmacy supply products bearing the designation 'P' from pharmacies, where they are dispensed under the supervision of a registered pharmacist. General sale list products may be sold through general retail channels, such as supermarkets, convenience stores, petrol stations and the like. These products bear the designation 'GSL'.
There are no UK rules governing the classification of medical devices that restrict their sale to the public.
xii Imports and exports
The United Kingdom's regulations governing the import and export of medicinal products generally reflect those at EU level, although Brexit has made the rules somewhat more complex. Unless products are intended only for trans-shipment via the United Kingdom, they must be imported by the holder of a manufacturer's authorisation or (as explained above), if importation is from an approved country into Great Britain, the holder of a wholesale dealer's licence. Products may only be exported by authorised manufacturers or distributors.
xiii Controlled substances
The Misuse of Drugs Act 197112 and subordinate legislation, including the Misuse of Drugs Regulations 2001,13 implement the UN Single Convention on Narcotic Drugs 1961 and the UN Convention on Psychotropic Substances 1971 into UK law. A 'domestic licence' is required to produce, possess, supply or offer to supply any controlled substance. Any person that intends to import or export a controlled substance must also obtain an import or export licence for the particular consignment, as applicable. The Home Office is responsible for issuing controlled substances licences in England and Wales. A domestic licence holder may only supply controlled substances to persons authorised to possess such substances; for example, registered pharmacists.
A breach of the Medicines Regulations is in most cases a criminal offence, and the MHRA has an Enforcement Division that considers and manages prosecutions. When the MHRA identifies a potential breach of the legislation, a letter is sent to the individual outlining the Agency's provisional view. The letter will generally list the potential breach or breaches and any public health risk identified where appropriate, along with any action the MHRA requests the company to take. The process to resolve these issues tends to be informal, with individuals agreeing to take voluntary action, so prosecutions are rare. Offences under the Medicines Regulations are usually triable either way (i.e., in summary proceedings before magistrates or on indictment before a crown court judge and jury, depending on the seriousness of the breach). They usually carry a penalty of a fine on summary conviction, or an unlimited fine and the possibility of up to two years in jail on indictment.
When the PMCPA Panel rules there is a breach of the ABPI Code under the self-regulatory scheme, the company concerned must give an undertaking not to repeat the offending advertisement or activity. The company, whether a member of the ABPI or not, must also pay an administrative charge of £3,500 per matter (or £4,500 per matter for non-members) where it accepts the Panel's decision that it breached the Code. The charge increases to £12,000 per matter (or £13,000 per matter for non-members) where the company appeals the Panel's decision and is unsuccessful. Additionally, if companies are ruled in breach of Clause 2 they must pay £4,000 towards the cost of advertising that fact in the relevant press. At the conclusion of a case, the PMCPA will also publish a detailed case report in its Code of Practice review and on its website.
The MHRA is responsible for ensuring compliance with the Medical Devices Regulations, with new powers to enforce civil sanctions under the Medicines and Medical Devices Act 2021.
The main sanction under the ABHI Code for non-compliance is negative publicity. An administrative charge is also payable. However, there have been no complaints procedures under the Code and the level of the administrative charges payable has not yet been determined.
Pricing and reimbursement
The NHS is primarily funded by general taxation. The NHS consists of four individual systems: NHS England, Health and Social Care (HSC) in Northern Ireland, NHS Scotland and NHS Wales.
The NHS pricing and reimbursement process is complex and not uniform. Different models are in place depending on whether the product is branded or generic and is used in primary care (e.g., dispensed at a community pharmacy) or secondary care (e.g., use in a hospital). As a rule of thumb, the NHS leaves it to market forces to regulate the price of generic medicines; whereas more formal structures are in place for branded and innovative products.
A product usually receives an NHS 'list price' through a consultation with the Department of Health and Social Care (DHSC). The DHSC affords manufacturers freedom to set the price of innovative, branded medicines. This price is published in the Drug Tariff (or incorporated into the tariff for hospitals). Although this process sets the headline price, branded medicines are subject to an additional layer of price controls and rebates, either through statute (the Statutory Scheme) or the Voluntary Scheme for Branded Medicines Pricing and Access (Voluntary Scheme) (both discussed further below).
As to reimbursement, the National Institute for Health and Care Excellence (NICE) assesses products to determine whether they are cost-effective and should be reimbursed by the NHS. NHS health service providers are expected to make funding available for products recommended by NICE.
ii Price controls and rebates: voluntary and statutory schemes
The Voluntary Scheme (VPAS) is an opt-in arrangement negotiated between the DHSC14 and the branded pharmaceutical industry represented by the ABPI. The Voluntary Scheme commenced in 2019 and will run to the end of 2023. The VPAS is the latest iteration in a sequence of historic voluntary pricing and rebate schemes agreed between the ABPI and the DHSC. The Voluntary Scheme prevents companies increasing their product list price without the prior approval of the DHSC. It also requires member companies to pay a rebate to the DHSC, based on a percentage of sales made to the NHS. The payment percentage is the same for all members and calculated by reference to sales trends and forecasts and an 'allowable' growth rate agreed between the ABPI and DHSC. The Statutory Scheme applies by default to any manufacturer of branded medicines who is not a member of the Voluntary Scheme. In their current guise, both schemes aim to be 'broadly commercially equivalent'. The Statutory Scheme also contains controls on price growth and a rebate mechanism. There are some differences, for example in terms of the rebate percentages and exemptions that apply under each scheme. The Voluntary Scheme can be the more advantageous to manufacturers of products containing new active substances.
iii National Institute for Health and Care Excellence
NICE performs technology appraisals of medicines and medical devices and draws up clinical guidelines for the NHS in England (and often also Wales). There are analogous procedures for other parts of the United Kingdom.
Under the National Health Service Act 2006, NHS entities must provide funding for medicines used in accordance with a favourable NICE appraisal determination, but are not precluded from reimbursing products that NICE has not recommended.
NICE appraises individual or multiple products, technologies and procedures and develops guidelines for the NHS. In doing so, NICE applies classical health technology assessment (HTA) methods. NICE aims to appraise new technologies with a significant impact for the NHS, patients and treatment. Where necessary, NICE commissions an independent academic centre known as an assessment group to review available evidence, including submissions by manufacturers, and prepare an evaluation report. NICE has a fairly rigid approach to assessing cost-effectiveness. It determines the quality-adjusted life year (QALY) associated with a technology and uses that to calculate the cost per QALY saved (i.e., incremental cost-effectiveness ratio (ICER)). NICE will favour interventions with a lower ICER. If the ICER is less than £20,000, NICE will usually recommend reimbursement. For ICERs up to £30,000, it will often exercise its discretion to recommend a product, but above this threshold, it is unlikely to recommend a product unless there are extenuating circumstances.
NICE has developed a highly specialised technology (HST) process, which is a variation of its existing processes designed to evaluate technologies for extremely rare conditions, essentially ultra-orphan medicines. NICE will recommend funding for HSTs with an ICER of less than £100,000 per QALY gained although it has discretion in certain circumstances to recommend products above that threshold, usually up to ICERs of £300,000. However, a medicine can only be appraised through the HST process if it satisfies narrow criteria. These include not only that the product is ultra-orphan but also that treatment is concentrated in very few centres in the NHS.
A partnership between NHS England, NICE, Public Health England and the Department of Health and Social Care also operates the Cancer Drugs Fund (CDF). NICE can recommend a drug for use in the CDF if it has the potential to satisfy the criteria for the standard health technology assessment process, but where there is significant clinical uncertainty that needs further investigation (i.e., through data collection in the NHS or clinical studies). The CDF provides an interim funding mechanism, often while a company gathers additional data to demonstrate the cost or clinical effectiveness of its drug.
In June 2021, the NHS announced the formation of a new £680 million ring-fenced Innovative Medicines Fund (IMF). The IMF will operate on similar principles to the CDF, but this time for treatments for rare and genetic diseases. The fund would offer an interim reimbursement mechanism for clinically promising treatments while further data are gathered to enable NICE to make a final determination.
NICE is currently in the process of reviewing its methods and procedures, which are expected to change significantly in future.
iv Medical devices
There is no formal scheme in the United Kingdom that governs the pricing and reimbursement of medical devices. Some devices are listed in the Drug Tariff, but these are largely consumable devices used by outpatients. Many other devices are reimbursed as part of the cost of NHS procedures under the Payment by Results system of tariffs. However, NICE performs some technology appraisals of medical devices.
Administrative and judicial remedies
It is possible to challenge the decisions of national public authorities, such as the MHRA or NICE, by judicial review. This is a procedure by which courts examine the decisions, actions or failures to act of a public body, subject to general principles of administrative law. Before seeking judicial review, the applicant must have exhausted all other avenues of redress, such as internal or administrative appeal procedures. In addition, the relevant act and body must be amenable to review, the claimant must have 'sufficient interest in the matter to which the application relates',15 or legal standing, and the claim must be commenced 'promptly and in any event not later than three months after the grounds to make the claim first arose'.16
The grounds for judicial review are constantly evolving but, in general, the courts will consider whether decisions or acts of a public body are illegal, irrational or procedurally unfair.17
There are three specific discretionary remedies for judicial review proceedings: quashing orders, prohibiting orders and mandatory orders. A claimant may also seek a declaration, a stay or injunction and, in certain circumstances, damages. Claimants typically seek a quashing order to set aside the public body's decision, together with a mandatory order directing the public body to take the decision again in accordance with the court's judgment.
Financial relationships with prescribers and payers
The Medicines Regulations contain a broad prohibition on the offer to healthcare professionals of unlawful inducements to prescribe. However, the prohibition excludes financial trade practices, such as discounts, that were in common use in the industry before 1 January 1993.
The Blue Guide and the ABPI Code clarify or establish additional requirements governing interactions with payers and prescribers. A new version of the ABPI Code was published in 2021 and was subject to a substantial overhaul. For example, the ABPI Code also governs the offer of inducements to administrative staff and prohibits promotional aids, except for inexpensive items for patient support. The ABPI Code also contains guidelines governing certain interactions between companies and NHS entities.
ii Medical devices
There are no specific UK rules that govern the interaction between medical devices companies and healthcare professionals.
The ABHI Code includes guidelines and a question-and-answer document on the minimum standards device companies should comply with when interacting with healthcare professionals, including payers. The provisions of the ABHI Code are based on the EU code of practice (the Eucomed Code) and therefore the national principles reflect the EU position on ethical communications and interactions with prescribers and payers.
iii Anti-bribery legislation
Most healthcare professionals, administrative staff and payers in the United Kingdom are government officials, employees or contractors. Companies should therefore also be mindful of anti-bribery legislation, such as the UK Bribery Act 2010.18
Special liability or compensation systems
With the exception of a specific vaccine injury compensation scheme and the implementation of EU rules governing compensation for clinical trial related injuries, there are no specific pharmaceutical injury compensation rules in the United Kingdom.
The Vaccine Damage Payments Act 1979 (VDPA)19 provides a statutory compensation scheme for individuals who can demonstrate that they have suffered a severe mental or physical disability caused by a vaccination against a specific disease. The VDPA scheme applies only to vaccinations for specified diseases listed in the VDPA or diseases recommended by the Secretary of State for Health as falling under the scope of the VDPA scheme.20 The scheme is rarely used because to claim the statutory tax-free payment of £120,000, individuals must show that they were at least 60 per cent disabled by the vaccination.
ii Medical devices
There is currently no national scheme or system to compensate individuals injured by medical devices.
Transactional and competition issues
i Competition law
Although the UK has left the EU, the provisions of the UK Competition Act 1998 closely reflect those found in Articles 101 (anticompetitive agreements) and 102 (abuse of dominant market position) of the Treaty on the Functioning of the European Union, many of the considerations and issues outlined in the European Union chapter apply equally in the United Kingdom.
The Competition and Markets Authority (CMA) is the body with responsibility for policing activities that affect trade within the United Kingdom, or regions within the United Kingdom. The CMA has recently been reviewing certain pricing practices in the pharmaceutical industry, particularly the practice of de-branding (or genericising) drugs so that they are no longer subject to price regulation through normal control mechanisms, such as the Pharmaceutical Pricing Regulation Scheme (PPRS). For example, at the end of 2016, the CMA fined pharmaceutical companies Pfizer and Flynn Pharma nearly £90 million for abusing their dominant position by charging excessive prices to the NHS for an anti-epilepsy drug, although this was overturned on appeal. A number of other investigations relating to excessive and unfair prices are ongoing in the United Kingdom. The CMA has also focused on 'pay-for-delay' agreements, issuing its first pay-for-delay infringement decision on 12 February 2016. It fined GlaxoSmithKline (GSK), Generics UK Limited (GUK), Merck KGaG (GUK's former parent company), Actavis UK Limited, Xellia Pharmaceuticals ApS and Alpharma LLC a total of £45 million for delaying market entry of generic versions of GSK's anti-depressant Seroxat (paroxetine) in the United Kingdom. The decision was appealed to the UK Competition Appeal Tribunal (CAT), which, following a reference to the Court of Justice of the European Union (discussed in the EU chapter) dismissed the appeal. The CMA also investigated a discount scheme that Merck Sharp & Dohme (MSD) operated for its product Remicade, among suggestions that it might have restricted competition for 'biosimilar' versions of infliximab. However, on 14 March 2019, the CMA closed its investigation because MSD's scheme was not likely to have exclusionary effects. In July 2021, the CMA handed out record fines of £260 million to Auden Mckenzie, Actavis UK (previously Accord-UK) and a number of generics for breaches of competition law involving charging excessive pricing and entering into 'pay-for-delay' market sharing agreements.
ii Transactional issues
The considerations and issues outlined in the European Union chapter apply equally in the United Kingdom.
Brexit has had significant implications for the pharmaceutical and medical devices industries in the United Kingdom and for international companies operating in the United Kingdom. For example, it has meant that companies have had to rearrange their supply chains and contend with diverging regulatory frameworks between the United Kingdom and European Union. Some of the key developments and potential changes are set out below.
i Trade and Cooperation Agreement
On 24 December 2020, the EU and the UK agreed to a Trade and Cooperation Agreement (TCA). The TCA sets out the new arrangements for trade of goods, including medicines and vaccines, which allows goods to continue to flow between the EU and the UK. On 29 December 2020, the Council of the EU adopted the decision to sign the TCA and the EU and UK signed the TCA on 30 December 2020. The TCA is to be provisionally applied from 1 January 2021 and was in force from 1 May 2021. The UK Parliament approved the European Union (Future Relationship) Act 2020 (which implements the TCA into UK law).
ii Northern Ireland Protocol
As noted above, the Northern Ireland Protocol means that certain EU laws still have effect in Northern Ireland. One of the consequences of the Northern Ireland Protocol is that goods can flow freely between the Republic of Ireland and Northern Ireland but goods arriving into Northern Ireland from the rest of the UK are subject to controls and checks to ensure they comply with EU standards. Northern Ireland gets most of its medicines from Great Britain and so far, medicines entering Northern Ireland from Great Britain have benefitted from a grace period, meaning that additional regulatory checks and requirements currently do not apply. However, at the time of writing, these grace periods are due to run out shortly. As such, many generic medicinal products (with low profit margins) have been put on notice of their withdrawal as it would be too costly to comply with both UK and EU regulatory requirements.
In October 2021 the European Commission proposed a bespoke arrangement for medicines in Northern Ireland to deal with these issues but their position required that the UK should fully apply EU legislation on medicines – on quality, safety, efficacy, pharmacovigilance and batch testing and release – when issuing national marketing authorisations in respect of Northern Ireland. However, this is unlikely to solve the issue for medicines with tight profit margins as any extra regulatory burdens will threaten the economic sustainability of these supply chains. At the time of writing, the UK government and European Commission are currently in negotiations to try and resolve this issue going forwards. However, the UK government has noted it will use Article 16 to suspend parts of the deal if a solution cannot be found.
iii Consultation on the future regulation of medical devices
The MHRA published a 'Consultation on the future regulation of medical devices in the United Kingdom' that ran until 25 November 2021 (at the time of writing the MHRA are reviewing responses). The consultation was split into 15 chapters, which set out the proposal for a UK-wide regime to regulate medical devices (which would run in parallel to the EU rules). Many of the proposed changes seemed in line with those in the EU Medical Devices Regulation 2017/745 and EU IVD Medical Devices Regulation (EU) 2017/746 (IVDR). However, it is clear the UK intends to not simply follow the EU regulatory framework and rather aims for broader alignment with international standards (e.g., the IMDRF). The MHRA stated it intends the changes to the regulatory framework to come into force in July 2023.
1 Grant Castle and Sarah Cowlishaw are partners at Covington & Burling LLP.
2 The Human Medicines Regulations 2012 (SI 2012/1916), as amended.
3 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, as amended.
4 The Medical Devices Regulations 2002 (SI 2002/618), as amended.
5 The Active Implantable Medical Devices Directive 90/385/EEC, the Medical Devices Directive 93/42/EEC, and the In Vitro Diagnostic Medical Devices Directive 98/79/EC.
6 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No. 178/2002 and Regulation (EC) No. 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC.
7 Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU.
8 The Animals (Scientific Procedures) Act 1986 (Chapter 14), as amended.
9 The Good Laboratory Practice Regulations 1999 (SI 199/3106), as amended.
10 Regulation (EC) No. 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate for medicinal products, as amended.
11 The Patents Act 1977 (Chapter 37), as amended.
12 The Misuse of Drugs Act 1971 (Chapter 38), as amended.
13 The Misuse of Drugs Regulations 2001 (SI 2001/3998), as amended.
14 Pursuant to the powers conferred upon the Department of Health by Section 262 of the National Health Service Act 2006 (Chapter 41), as amended.
15 Section 31(3) of the Senior Courts Act 1981 (Chapter 54).
16 The Civil Procedure Rules 1998 (SI 1998/3132), Rule 54.5(1).
17 Council of the Civil Service Unions v. Minister for the Civil Service  A.C. 374. The list of grounds for review cited is not exhaustive and may be added to in the future.
18 The Bribery Act 2010 (Chapter 23).
19 The Vaccine Damages Payments Act 1979 (Chapter 17), as amended.
20 Section 2 of the VDPA.