Abstract
The UK laws regarding the licensing of medicines have been developed to reduce the likelihood of harm through their use. Unlicensed medicines lie outside that harm management process; they have additional risks and require professional responsibilities that are complex. Therefore, pharmacy practice applies risk management tactics that are specific to how it manages unlicensed medicines, especially in hospitals, where the risks of their use is at its highest. Due to increasing demand and costs - but static funding - healthcare in the UK's National Health Service is under stress and undergoing a period of transformation and cost savings. That transformation affects all areas of pharmacy practice and medicines procurement. Service leaders need to keep a focus on maintaining safety systems for unlicensed medicines through a period of change, including potential changes in roles and responsibilities.
Background to unlicensed medicines in the UK
Legal framework
In November 1961, serious limb deformities (phocomelia) were noted in a large number of newborns whose mothers had been prescribed thalidomide (1). Worldwide, the estimated numbers were 10,000, which included 5,000 in the UK alone. This problem triggered a number of actions.
The UK Ministry of Health, within a few days, warned patients to stop taking the medicine.
In August 1962, the Association of the British Pharmaceutical Industry (ABPI) set up an Expert Committee on Drug Toxicity.
Also in August 1962, the UK Government Standing Medical Advisory Committee set up a joint sub-committee on the safety of drugs, which was chaired by Lord Cohen.
In March 1963, the Cohen Report was published. It recommended that a Committee on the Safety of Drugs (CSD) be established with 4 sub-committees to consider toxicity, clinical trials, therapeutic efficacy, and adverse drug reactions. The report also noted that additional areas of drug safety concern outside of the CSD remit existed, which were:
the control of the quality of drugs;
the control of over-the-counter (OTC) sales of medicines;
the use of approved names;
the regulation of therapeutic claims.
In January 1964, the CSD started its work and set up voluntary working with the ABPI to cover its areas of responsibility. It also set up the “Yellow Card” adverse reaction reporting scheme.
The Medicines Act 1968 brought all aspects of control of medicines into one legal framework. It required that all medicines then in use must be reviewed, and, if appropriate, be licensed and given marketing authorizations by September 1971. By that date, of the 30,000 medicines that had previously been on the market, 5,000 had been licensed. Also from 1971, all new medicines were required to be assessed for safety, quality, and efficacy by a licensing authority: the Medicines Control Agency (MCA).
In 2003, the MCA merged with the Medical Devices Agency to become the Medicines and Healthcare Products Regulatory Agency (MHRA) (2), which continues to license and regulate the use of medicines in the UK. Its remit is to:
ensure that medicines, medical devices, and blood products meet appropriate standards of safety, quality, and efficacy;
ensure that the supply chain for those items is safe and secure;
promote harmonization of international standards for those items;
educate the public and healthcare professionals about the risks and benefits of such products;
support innovation, research, and developments beneficial to public health;
influence UK, EU and international regulatory frameworks so they are risk proportionate and effective in protecting public health.
New medicines for use across the whole of the EU, rather than just within the UK, are licensed with a centralized procedure by the European Medicines Agency (EMA). Each licensing agency is advised by expert groups in making determinations about licensing. In the UK, the CSD was replaced by the Committee on Safety of Medicines, which, in turn, was superseded in 2005 by the Commission on Human Medicines as a sub-committee of the MHRA. The EMA is advised by the Committee for Medicinal Products in Humans.
Professional responsibilities
The majority of medicines prescribed in the UK are licensed, and should only be prescribed in accordance with the terms of license as detailed in the Summary of Product Characteristics (SPC).
However, there are clinical situations where there is no licensed product available to provide the best treatment option for a given patient (3). Therefore, UK prescribers may prescribe unlicensed medicines where, following an assessment of the patient, the prescriber determines that for medical reasons it better fulfils the specific needs of that patient. The prescriber must be satisfied that there is sufficient evidence to demonstrate its safety and efficacy, that he/she takes responsibility for overseeing the patient's care, or that arrangements are made for another suitable prescriber to do so. He/she must make a clear, accurate, and legible record of all medicines prescribed and the reasons for such prescribing. The prescriber must also give the patient sufficient information about the medicine to make an informed decision about its use in accordance with guidance on informed consent (4).
The role of the pharmacist regarding unlicensed medicines is authorized within the Medicines Act 1968 within an exemption (section 10) from the requirement for a medicine to have a marketing authorization license. That exemption allows the pharmacist to prepare or dispense a medicinal product in accordance with a prescription or to supervise such preparation or dispensing.
Historically, unlicensed products were prepared extemporaneously within individual community or hospital pharmacies, but in recent decades such work has been undertaken by specialist manufacturers who hold licenses granted by the MHRA who inspect their premises, processes, and quality systems. This provides better quality and safety as well as economies of scale in both the production and access to highly specialized manufacturing and quality assurance skills. However, even when using such a specialist manufacturer, the supplying pharmacist retains a duty of care towards the patient and remains responsible (5) for ensuring that:
the supply is in the best interests of the patient;
the product supplied is the product prescribed;
the product supplied is produced to an acceptable standard and quality.
Therefore, the supplying pharmacist must be sure that the patient's needs cannot be fulfilled by a licensed product, and must be prepared to challenge the prescriber to ensure that is the case. He/she should also use sources where the assurance of service and product quality can be gained (e.g., through MHRA licensing) and, where appropriate, obtain product quality assurance reports and/or statements of product conformity to prove such quality and compliance with the prescription.
Types of unlicensed medicines
Manipulated products
Any product that does not have a product license recognized by a given country, or that differs from an original licensed product, is not licensed. Thus, any product that may have been licensed, but which has changed prior to supply or administration to a patient in a manner not detailed within its SPC is not licensed. This change can be necessary for a number of reasons; for example, crushing tablets or opening capsules to administer a medicine through a nasogastric tube, or putting more than one injectable product into a syringe or intravenous (IV) bag. In such cases, there are additional risks to the patient and to the healthcare professional, and any change to the product must be done in accordance with agreed and ratified procedures.
Specials
In cases where licensed products need to be manipulated prior to use, or need to be made de-novo for an individual patient, it is important that the product prepared is consistent in formulation to ensure a consistent clinical response. Whenever possible, such manipulation/preparation should be undertaken using a consistent formula and process, and by staff well trained in such work. To achieve this aim, the preparation is often subcontracted by the supplying pharmacist to a third-party “specials” manufacturer who is licensed, monitored, and regulated by the MHRA. This helps the supplying pharmacist to ensure product quality and consistency, and to demonstrate that they have fulfilled many of the professional obligations noted previously.
“Off-label” medicines
SPCs of licensed products, detail - among other things -the indications for use and the patient age group. Each SPC reflects the successful license application, which, in turn, is based on the clinical trials it has been subjected to. These trials are determined by the likely return on investment that the drug company should achieve. Drugs that may be efficacious in rare diseases with few patients may never by trialed and licensed for such use. Similarly, significant costs may be added to undertake clinical trials in the young or the elderly whose biochemical and physical processes differ from the population of 18- to 65-year-olds. Therefore, it is not uncommon (and in children very common) for licensed medicines to be prescribed and supplied in unlicensed indications, dosages, and patient groups. Such use is commonly described as “off-label” use.
Risks and their management
All medicines carry risks, be they side-effects, interaction with other drugs or foods, or through misadventure or error in their use. The licensing and regulatory system provides a significant level of assurance about product quality, a high level of understanding of likely problems that may arise in their use, and how to manage such problems. Unlicensed medicines do not provide such surety; therefore, they carry a range of additional risks, which are outlined in the following sub-sections.
Clinical
As an unlicensed medicine has not been subject to clinical trials, its use may carry additional risks. For example, a narrow therapeutic index where dose variation may be critical and where safety processes for its use have not been defined, or it may carry unanticipated side effects or lower than expected efficacy. It is because of that increased risk that the healthcare professionals involved need to ensure the patient is appropriately informed and able to participate in the decisions about whether and how the medicine in question should be used. There is also an obligation to ensure that appropriate clinical monitoring is undertaken to identify and correct any problems, should they occur, and that records are kept and are accessible to other healthcare professionals that are or may become involved in the patient's care.
Product quality
The process of licensing and regulating drugs and manufacturers includes a review of premises, processes, quality assurance results, error management, and product recall systems. Therefore, a licensed product will be proven to be of high and consistent quality with risk management strategies, which will give assurance to the patient, the prescriber, and the supplying pharmacist that it is routinely safe. An unlicensed product does not have the same level of surety, so the supplying pharmacist, who is responsible for the product quality, needs to ensure that the risk of poor product quality and/or variability is minimized.
Continuity of care
Patients in the UK will often move between care sectors, such as home, hospital, or care home. Each location is likely to have different healthcare professionals supporting the patient, as well as different pharmacists supplying the medicines. As such, the potential is high for communication failures and inconsistency in the source of medicines. Where the medicines involved are licensed, be they branded or generic, they are known to be produced to a consistent formulation and standard. However, where unlicensed medicines are involved, the manufacturer may change, and the product quality and consistency be threatened. This is particularly the case with transfers of care between the hospital and the community.
The hospital is likely to use a specials manufacturer or medicines importer as its source of unlicensed medicine. The community pharmacist, who is responsible for supplying the medicines following the patient's discharge from hospital, is not obliged to use the same medicinal source as the hospital. Indeed, some large community pharmacy chains have their own manufacturing facilities and they require their pharmacists to use them as their first option. Thus, unintended product variation can occur.
Financial
Production and acquisition costs
Unlicensed medicines are normally manufactured as individual units or small batch runs. Therefore, there is a significant diseconomy of scale, which means that unit costs are often higher than similar traditional medicines.
When the unlicensed product must be obtained from abroad, hospital and community pharmacies do not normally have importation licenses, and will subcontract sourcing to specialist firms. Therefore, such medicines carry additional transport costs as well as third-party agency fees. The prices will also vary with currency exchange rate changes, which may increase unit costs.
Payment systems
Coding and hospital tariffs
In UK, provider hospitals receive payment from clinical commissioners for episodes of care, whether they are inpatient, outpatient, emergency, or diagnostic. These episodes each have a payment by results (PBR) tariff that relates to the complexity and cost of providing the care as defined in computerized clinical codes. This tariff is meant to cover the direct and indirect care costs of each episode, such as staff, hotel and food, diagnostic, equipment, and drugs.
However, many new drugs coming onto the market are very expensive, so in areas where new innovative treatments are being developed and care pathways are changing, the total costs due to the drugs can significantly exceed the tariff income a provider will get. In such cases, the drug costs are excluded from the tariff and the provider is paid a tariff for the attendance or hospital stay, and separately bills the commissioner for the drug costs. These are called PBR exclusions (PBR exc). However, the range of such PBR exc. payments have to be defined or agreed by the care commissioner. If a drug is replaced by another more expensive one, which is not a defined PBR exc. drug, then the provider hospital will be paid only the normal tariff rate and must cover any excess costs above the tariff. Therefore, unlicensed medicines that frequently cost more than routinely used drugs carry a financial risk to the hospital that provides them.
General practice
Hospitals are not routinely responsibility for the ongoing care of patients. It is normal for patients to be discharged back to the care of their general practitioner (GP). He/she is allocated an indicative budget to cover the drug costs for his/her practice's patients, which is closely monitored by the local care commissioners.
There are often financial incentives for remaining within or saving money from the practice's drug budget. Unlicensed medicines can carry a financial risk to GP practices; therefore, there may be a disincentive for GPs to continue to prescribe expensive drugs initiated in secondary care.
Additionally, as the prescriber carries clinical, professional, and legal responsibility for the drugs used, if a GP feels that they have no experience of (and do not know enough about) a drug to accept such responsibility, they can refuse to prescribe it.
Therefore, on such professional grounds, an unlicensed drug initiated in hospital may be refused by the GP who will need to find a suitable alternative or pass the ongoing prescribing back to the hospital specialist. However, hospitals do not have systems for repeated prescribing and supply, which require the patient to keep attending the hospital to obtain new prescriptions. Not only is this inconvenient for the patient, but also it wastes hospital capacity and raises additional commissioner costs for the extra attendances.
National drug tariff and community pharmacy
When licensed, the UK's National Health Service (NHS) items are dispensed by non-hospital community pharmacies. The pharmacy pays for the goods used and then claims back the cost each month. The price paid for any given medicine is defined in the drug tariff, which is under continual review and is updated each month. Prior to 2011, unlicensed medicines were not included in the drug tariff, and pharmacists were reimbursed on the basis of invoices they paid for the individual product.
In the early 2000s, concerns began to be discussed within the NHS about the possible abuse of the pharmacy reimbursement system. There were reports of some companies with wholesaler licenses acquiring specials at one price but providing community pharmacies with their own invoices at a different, inflated price. The community pharmacy then reclaimed the inflated price and paid the licensed wholesaler, at his invoice price, who subsequently gave the community pharmacy a retrospective rebate for some of the difference between the initial and the inflated prices. In 2010, this became known outside of the NHS circle through reports in the media (6). There were anecdotal reports from some commissioner pharmacy teams regarding items with an initial price of approximately £100 being claimed with a final value in excess of £1,000. NHS Counter Fraud Services were asked to investigate this by some local healthcare commissioners, which they did. These investigations reported that, within the terms of the NHS community pharmacy contracts and reimbursement systems that were then in place, this was possibly dubious practice but was not fraud or otherwise illegal.
Therefore, to address this financial risk to the NHS, arrangements were put in place to develop drug tariff prices for higher volume/cost unlicensed specials, and they were, for England and Wales, enacted in 2011 with the top 100 being added to the drug tariff. Similar arrangements were also set up in Scotland and Northern Ireland, which have a greater level of devolved power and separate reimbursement systems. This was further developed, and arrangements for claiming reimbursement for unlicensed specials have been more tightly defined and monitored. Over subsequent years, this reduced the unit costs of unlicensed specials included in the drug tariff, it saved the NHS significant funds, and it reduced the risk of criticism of both the pharmacy and the NHS (7).
Hidden costs
As unlicensed medicines carry extra risks and require non-standard procurement processes, they require the controlling pharmacist to develop and use specific policies and/or procedures. This allows the healthcare provider to minimize the risk to patients and to demonstrate to regulators that they have robust and legal processes.
Preparing, ratifying, and keeping such policies and procedures up to date and then auditing compliance with them requires significant extra staff time. This is rarely ever quantified, but it can be a considerable extra ongoing cost for the healthcare provider. However, common sense normally prevails with different organizations keeping this complexity proportionate to the volume and/or clinical risk of the unlicensed medicines used or supplied by their organization. Thus, in hospital services, the resources applied to this are higher than in individual community pharmacies, and they can be a drain on resources in hospital pharmacies where staffing shortfalls exist.
Sources of unlicensed medicines
The source of unlicensed medicines is determined by the type of unlicensed medicine involved. The commonly used sources are listed below.
In-House: Medicines manipulated prior to use are normally prepared in-house either within pharmacy departments (e.g., ready to use injectables) or at the bedside/in theatres (e.g., mixed products in IV bags or syringes).
Importer/Wholesaler: Where a medicine is not licensed locally but exists in a licensed form in another country, most pharmacists will use a registered importer/wholesaler to identify a suitable source and manage the administrative hurdles that the import and export of medicines require.
Specials Manufacturer: Many unlicensed medicines are required where the supplying pharmacy does not have the capacity, skills, or equipment necessary for their production. These are sourced from registered specials manufacturers (e.g., liquid formulations of licensed medicines only available in solid oral form, or creams/ointments, or aseptic/sterilized products).
Licensed Product Manufacturer: Manufacturers who are developing new products may supply them on compassionate grounds, prior to licensing, for participants of clinical trials.
Additionally, in the UK, there are new arrangements for Early Access to Medicines Scheme (EAMS) for promising new agents to support innovation and gain experience and enhanced information about the product in use. In this case, a risk/benefit analysis is undertaken by the regulator on the basis of early clinical data. If the product is granted Promising Innovative Medicine (PIM) status, it may be used prior to full licensing. Initially, this is for 1 year, but it can be renewed (8).
Managing risks
As noted above, in the UK, a number of risks associated with unlicensed medicines are addressed through national policies and legislation, such as cost containment and regulatory oversight of care providers, unlicensed medicines' manufacturers, and importers.
The area of healthcare that carries the greatest risk to individual patients is hospital care. This is due to the larger volume and range of unlicensed products handled, the acuity of patient need, and it being the area where most unlicensed medicines are initiated and where patients are stabilized on treatment. Therefore, in UK hospitals, more highly structured risk management strategies and tactics are employed as a subset of the wider clinical risk management processes. The responsibility for such strategies and tactics is delegated to the Director of Pharmacy/Chief Pharmacist, although day to day activities may be further delegated to a suitably experienced pharmacist or a medication safety officer.
Each provider Trust has a specific policy that will define the scope of unlicensed medicine use, and the roles and responsibilities regarding their prescription, acquisition, supply, use, and monitoring. This is based on:
legal requirements;
guidance from professional bodies, such as the General Medical Council and the Royal Pharmaceutical Society of Great Britain;
recognized best practice as detailed by expert groups, such as the MHRA, national Specialist Pharmacy Services Procurement, and quality assurance groups.
Each specific policy contains requirements for validating the need for an unlicensed medicine, for ensuring that the source of the medicine provides the lowest risk of poor or variable quality, and for record keeping. It will define how communications and hand-offs related to unlicensed medicines should be handled to ensure continuity of care when patients are discharged from one care provider/location to another. It will also define audit- and governance-reporting requirements.
From a supplying hospital pharmacy perspective, the key issue will routinely be the decision of which source of supply to use. This is based around a hierarchy of risk for the possible types of product available.
The decision-making flow chart related to this and other clinical risk management is shown in Figure 1.
Unlicensed medicines decision tree.
The hospital pharmacy will have decided on which importing agent and specials manufacturer they will routinely use. It is easier to get a responsive and supportive service from those with whom a long-term business relationship has been established. Therefore, many hospital pharmacies handling a lot of unlicensed medicines will have a prime vendor agreement with one of each type of supplier, and will have very clear service specifications that provide clarity about the responsibilities, which help prove to regulators that good practices are in place. This also reduces hassles for the pharmacy procurement staff as the majority of requirements can be fulfilled without the need to contact all possible sources of supply. Such staff are often under pressure as they are fully occupied with routine procurement tasks of standard medicines and with ensuring high-value drug cost reimbursement from the commissioners. Thus, such prime vendor agreements, through the freeing of staff time, help to reduce the hidden cost burden in this area of pharmacy practice.
The future of unlicensed medicines
Costs as a driver for unlicensed medicines use
Healthcare is a high innovation industry - especially around the research and development of new medicines. As new medicines come onto the market, the use of historic ones declines until they become unprofitable for the manufacturer to continue to produce and supply. However, there will remain a small number of patients who either cannot use the newer medicines or whose condition is fragile and they are stabilized on the historic medicine. Therefore, maintaining access to the old medicines is clinically justified and they have to be obtained on an unlicensed basis.
There has been a rising trend for manufacturers to sell on their marginally profitable, old drug marketing licenses to a different marketing company who then apply a significant price increase. There are other unlicensed medicines where a marketer can gain a license and become a monopoly supplier of that product. In extreme cases, the additional cost to the NHS can run into tens of millions of pounds. Healthcare providers and commissioners recognize that the diseconomies of scale or licensing costs mean that some medicines of these types warrant an increased price, but in recent years they have struggled to see the justification for some extreme increased costs, which seems like sharp practice. Such concerns have increased as financial deficits in the NHS have grown, and overall drug cost inflation has greatly exceeded other types of healthcare cost inflation.
Therefore, if an unlicensed medicine is available as a clinical alternative to the licensed product, and is significantly cheaper, then there is a conflict between regulator and professional body guidance about always using the licensed drug and the drive to minimize costs. In recent years, risk assessments have been undertaken by local healthcare providers and commissioners, which have shown that the clinical risks of using the unlicensed product preferentially to the licensed one are low while the financial risks are high; therefore, the use of the unlicensed medicine has continued.
Drug price/cost increases have become an increasingly politicized issue and undoubtedly there will be more moves to find a balance between clinical and financial risks rather than always using a licensed product regardless of cost.
NHS efficiency reviews
Healthcare is under stress worldwide. Demand is increasing with an aging population and political and consumer demands for enhanced access. Plus, costs are increasing not only through the adoption of innovative and improved treatments, but also through underlying healthcare inflation, which is higher than in other areas of the economy. At the same time, economic and political drivers have meant that the NHS is likely to be subject to static funding over the 2010-2020 decade.
This mismatch in increased costs and static funding means that the NHS in England developed a strategic plan (9) - the “5-Year Forward View” - to enable the NHS to respond to increasing healthcare service demands within an austerity funding formula. This requires service transformation and savings of £22 billion by 2020. As part of this savings work, Lord Carter of Coles was commissioned to undertake a review (10) of efficiency in hospitals. Another stream of the 5-Year Forward View work in the NHS is to plan and implement transformation of care provision across all healthcare sectors. This is being done through 44 locality-based Sustainability and Transformation Plans (STPs).
The Carter Review involved a review of the workforce, hospital pharmacy and medicines, estates management, and procurement systems. His report identified significant variations in practice and levels of efficiency with a potential overall savings of up to £5 billion of which £800 million could be saved in medicines spending through better use of pharmacy staffing and practices.
As part of reducing these variations, a “model hospital” was defined, including a need to transform hospital pharmacy services. For pharmacy, this involves maximizing the input of pharmacy staff and practice into clinical decision making, and providing front line, patient-facing clinical services. Non-clinical services use 55% of the pharmacy staff resource. These supportive services are considered to be infrastructure elements that need to be reviewed and restructured to minimize the variations and costs, and to free pharmacists from such services so the costs can be added to the clinical pharmacy staffing.
Procurement of medicines is one such infrastructure service that will change with increased electronic purchasing and invoice management, the sharing of service across NHS organizations, and the sub-contracting of work to third-party providers. It is likely that the procurement service will become more efficient in managing routine medicines, but will become more remote from the clinical pharmacy service and thus more likely to suffer from communication failures around non-standard drug procurement needs, such as those for unlicensed medicines.
Hospitals may try to offset the risks this will present by sub-contracting the supply to third parties. We may then have a scenario where procurement and supply bypass the hospital pharmacy, and the current participants in the unlicensed medicine supply chain (e.g., manufacturers, wholesalers, importers and homecare medicine providers) may develop an increased role in the sourcing and supply of medicines direct to patients on behalf of a large number of hospital providers. This may have additional benefits as they also have a presence in primary care, so this could free capacity in the community pharmacy, which is being required to provide expanded or new clinical services as part of the wider STP reviews of how NHS care is provided. This aims to break down barriers between the care sectors and move non-emergency and non-critical care out of the hospital environment.
Additionally, a current program is rolling out new posts for clinical pharmacists working within GP practices to support more effective prescribing and to provide direct clinical services. These posts have the potential to provide improved continuity of care and risk reduction around the use of medicines, if they work constructively with hospitals and community pharmacies. These posts could become the patients' advocate for their medicines-related needs and could coordinate the management of higher risk medicines (e.g., unlicensed medicines) across all care and third-party sectors.
Consumerism and patient information
It is a key principle in the NHS that patients should be appropriately informed about their treatment options and be party to decisions about their future care. This is summed up as “No Decision About Me Without Me.” However, issues related to unlicensed medicines and their relative risk can be complex, and historic paternalism in healthcare could mean this may not happen. Additionally, this principle should apply to the off-label use of medicines, but this may not be a feasible option as in some areas (e.g., pediatrics) the majority of medicines are used off-label. Therefore, a prescriber has to make a judgment call about which medicines to cover and which patients should be fully informed.
Governance systems (e.g., the Care Quality Commission) reviews are subject to variations between inspectors with some recognizing that such judgement calls are essential, while others may consider information provision to be an absolute requirement.
The world is becoming increasingly consumerist and this applies to individual patients, and even more so to patient lobby groups who are less likely to accept that the doctor and/or pharmacist knows best, and are rightly very wedded to the “No Decision About Me Without Me” principle.
Therefore, the informed patient principle, the governance drivers, and the consumerist drivers are leading to an increased need for supportive information to be made available for patients about the nature of unlicensed medicines, the need for them, the relative risks of them, and where to seek more advice/support if any concerns arise.
This need can be expected to grow in the future, but with the reorganization of the hospital medicine supply chain and the support services for clinical pharmacists, this need may be unfilled. It will be interesting to see how this will be accommodated and by whom. It may be through new players and roles coming into the supply system, through internet based information sources, or through the expanded clinical pharmacy services in hospitals and community locations. However, at present, this is not clear.
UK leaving the EU (BREXIT)
Another possible area of uncertainty will be the impact of the UK leaving the EU. Currently, licensing systems are shared and harmonized across the EU. In the UK, we will not know for at least 2 years whether there will be an agreement to maintain the current arrangements or if they will change.
I suspect that the UK approach to managing unlicensed medicines will only change if BREXIT changes drive a complete review of UK medicine licensing laws. However, with the UK having a long-standing and effective system through the MHRA, this is unlikely.
Footnotes
Financial support: None.
Conflict of interest: None.