Contributed By Arnold & Porter
This chapter sets out the current position in the UK under the applicable EU and national legislation.
As the reader will be aware, on 31 January 2020 the UK left the EU. The EU and the UK have ratified a Withdrawal Agreement establishing the terms of the UK withdrawal. This Agreement has been implemented in the UK by The European Union (Withdrawal Agreement) Act 2020, which received royal assent on 23 January 2020.
Under the Withdrawal Agreement, EU Law shall be applicable to and in the UK during the transition period, unless otherwise provided within the Agreement. The transition period is set to last up to the 31 December 2020. Thus, EU law governing life sciences product authorisation and exclusivity rights continues to apply to the UK during the transition period with some limited exceptions. This chapter refers to such exceptions.
Under the Withdrawal Agreement, during the transition period, pharmaceuticals and medical devices lawfully placed on the market of the EU27 or the UK, before the end of the transition period, may continue to circulate until they reach their end user. However, the Medicines and Healthcare Products Regulatory Agency (MHRA) will no longer act as a lead authority for marketing authorisation (MA) applications at the EU level, which in practice means that the UK cannot be a reference member state for MA applications made under the decentralised or mutual recognition procedures during this period.
The Withdrawal Agreement secures the exchange of information between UK and EU market surveillance bodies (including where requested in respect of conformity assessments by notified bodies (NB)).
In addition, all relevant files or documents relating to procedures led by the MHRA, including MA applications under Directive 2001/83/EC that were ongoing on the day before the entry into force of the Withdrawal Agreement, must be transferred to the competent authority of a designated member state. If requested by the certificate holder, information held by a conformity assessment body established in the UK, in relation to its activities as a notified body before the end of the transition period, must be made available to a notified body established in a member state, and vice versa.
The focus now is on the negotiation of a free trade relationship between the UK and the EU, which is intended to apply from 1 January 2021, once the transition period has finished. This will be based on the revised Political Declaration setting out the framework for the future relationship between the UK and the EU but at this stage the terms of such an agreement are unclear.
The regulation of medicinal products in the UK derives from EU legislation, principally Directive 2001/83/EC (the EU Directive), and Regulation (EC) 726/2004 (the EU Regulation). The key UK legislation is the Human Medicines Regulations 2012 (SI 2012/1916) (the Human Medicines Regulations).
The Human Medicines Regulations define a medicinal product as follows:
Currently, medical devices in the EU are regulated by three directives (the Medical Device Directives):
The MDD is applicable to all medical devices, which are defined as "any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of:
and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means."
This includes items such as heart valves, hip replacements, contact lenses, bandages, inhalers and certain software apps.
The AIMDD concerns active implantable medical devices, meaning any medical device which relies on a source of energy or power, other than that directly generated by the human body or gravity, which is intended to be totally or partially introduced, surgically or medically, into the human body or by medical intervention into a natural orifice, which is intended to remain there after the procedure. This includes devices such as pacemakers, insulin pumps and cochlear implants.
The IVDMD concerns any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens. This includes items such as pregnancy tests, blood glucose meters and HIV tests.
Before they could take effect, the MDD required transposition into domestic law. In the UK this was achieved by the Medical Devices Regulations 2002/618 (the UK Medical Devices Regulations). As a result of diverging interpretations, the EU framework has been applied somewhat inconsistently across the member states. To address this, in September 2012 the European Commission presented two legislative proposals on medical and in vitro diagnostic devices. This process culminated in two new directly applicable regulations being adopted 25 May 2017 (the Medical Device Regulations), namely:
The majority of the EU MDR and EU IVDR provisions will apply from 26 May 2020 and 26 May 2022, respectively. The information set out below is based on the UK's current legislation, except where stated otherwise.
The MHRA is an executive agency sponsored by the Department of Health and Social Care (DHSC). The MHRA acts on behalf of the UK Licensing Authority, comprising the Secretary of State, and the Ministers for Health, Social Care and Public Health or Safety, with the statutory responsibility to apply and enforce laws governing pharmaceuticals and medical devices in the UK. The MHRA is responsible for managing applications made through the national, mutual recognition or decentralised procedures. However, when an application for an MA is submitted through the centralised procedure, that falls within the remit of the European Medicines Agency (EMA). The EMA advises the European Commission in relation to the supervision of medicinal products authorised in the EU, including those authorised through the centralised procedure.
As mentioned, the UK Withdrawal Agreement provides for a transition period until 31 December 2020, during which the UK remains in the single market, in order to ensure frictionless trade until a long-term relationship is agreed. During the transition period, companies based in the UK can continue to apply for MAs via the centralised, decentralised or mutual recognition procedures.
NBs are private organisations that have been designated by an EU member state to assess whether manufacturers and their medical devices meet the requirements set out in the legislation. Manufacturers can apply to any NB within the EU for certification. On receipt of an application, the NB will conduct an assessment which, if successful, will result in the relevant certification being granted to the manufacturer. This certification allows manufacturers to place a European Conformity mark (CE mark) on their products, which in turn permits these products to be placed on the EU market.
In the UK, there are three NBs, namely:
The MHRA is responsible for ensuring that medical devices placed on the market and put into service in the UK meet the regulatory requirements. Accordingly, the MHRA:
Decisions of the MHRA can be challenged by way of judicial review in the Administrative Court, Queen's Bench Division.
In order to challenge a decision of the MHRA by judicial review, an application must be made promptly, and in any event within three months, of the decision to be challenged. This is a strict deadline that cannot be extended by agreement between the parties. In order to bring a claim for judicial review, the applicants must be able to show a sufficient interest in the matter to which the application relates. This will be shown where a decision of the MHRA directly affects the legal rights of enterprises to market or deal in their products, for example, refusal to grant an MA.
The court's permission is required to proceed with a claim for judicial review. The test for permission to be granted is whether there is an arguable case for judicial review that justifies full investigation of the substantive merits. An arguable case is considered to be one with a realistic prospect of success.
The court's function in judicial review is to assess the decision made by the regulator or public authority for legal error. The court cannot remake the decision or make factual determinations. The grounds for judicial review are evolving but can be summarised under four headings:
The judicial review rules and procedures apply equally to challenges concerning other products regulated by a public authority, such as food products.
There are three categories, or legal classifications, of medicinal products. These legal classifications determine the level of control over supply. In part, classification rests on how much healthcare professional (HCP) input is needed to diagnose and treat the conditions for which the medicine might be used. The underlying principle for classifying medicines is to maximise timely access to effective medicines while minimising the risk of harm from inappropriate use.
The three legal classifications are:
As discussed above, there are three main types of medical devices:
Medical devices are given a classification depending on the level of risk associated with their use. How a medical device is classified will depend on factors including the intended purpose of the device, how long it is intended to be in use for and if the device is invasive/surgically invasive, is implantable or active, or contains a substance which in its own right is considered to be a medicinal substance.
General medical devices and active implantable devices fall within the following categories:
All active implantable medical devices fall under the highest risk category (Class III).
In vitro diagnostic medical devices are currently categorised differently into four main groups, namely those which are:
However, the classification of IVDs has been revamped under the EU IVDR which, as discussed above, will be applicable on 26 May 2022.
Clinical trials of medicinal products are regulated by the Medicines for Human Use (Clinical Trials) Regulations 2004/1031, which implement Directive 2001/20/EC on the conduct of clinical trials (the Clinical Trials Directive) in the UK. Clinical trials must be conducted in accordance with good clinical practice, as well as the terms of the protocol, clinical trial authorisation and the ethics committee approval. The EU Clinical Trials Regulation 536/2014 had not entered into application at the time of the UK’s withdrawal from the EU and is unlikely to do so during the transition period. The EU Clinical Trials Regulation is, therefore, not incorporated into UK law through the European Union (Withdrawal) Act 2020. The UK government’s current position is that it will align, insofar as possible, UK law with the EU Clinical Trials Regulation once it comes into application in the EU (subject to the usual parliamentary approvals).
Clinical investigations for medical devices are regulated by the UK Medical Devices Regulations. As mentioned in 1.1 Legislation and Regulation, the EU MDR will enter fully into force on 26 May 2020 and will apply fully in the UK as of this date. The EU MDR contains updated provisions on clinical investigations, although these largely incorporate the current guidance into EU law, rather than introduce wholesale changes to the current rules. Under these rules, clinical investigations must be conducted in accordance with Annex X of the MDD (or Annex XV in the EU MDR once applicable), and any conditions imposed by the Secretary of State on the conduct of the trial.
Applications for a clinical trial authorisation for a medicinal product are made to the MHRA. It is also necessary to obtain approval from an appropriate ethics committee. A clinical trial can only be started if the competent authorities have concluded that the anticipated therapeutic and public health benefits justify the risks.
After receipt of a valid request for an authorisation, the MHRA will conduct an initial assessment within 30 days. At this time, the MHRA will either: (i) accept the request for the clinical trial authorisation; (ii) accept the request subject to conditions; or (iii) not accept the request, and provide reasons for its decision.
The ethics committee will review certain documents relating to the trial, especially the trial protocol; the informed consent form; the suitability of the personnel, investigator and facilities: and the investigator's brochure. In doing so, the ethics committee will consider the recruitment, compensation and consent of the subjects who will be taking part in the trial. The ethics committee has 60 days in which to form a view on the clinical trial and must then give a reasoned opinion to the applicant and the MHRA.
The MHRA must also be notified of clinical investigations for medical devices. A sponsor must notify the MHRA at least 60 days before starting the investigation. The MHRA will consider valid documentation and will assess the safety and performance of the device as well as the design of the clinical investigation to be carried out. A letter will be sent to the sponsor within 60 days with a decision (either being an "objection" or "no objection") as to whether or not the proposed clinical investigation can be carried out. In addition, an opinion of the ethics committee is required, following a similar process to that used for medicinal products.
In the UK, there are no independent obligations imposed on sponsors in relation to the publication of clinical trial data. Instead, the UK Clinical Trials Regulations refer to Article 11 of the Clinical Trials Directive, which states that member states have an obligation to enter certain information about trials conducted in their territory onto the European EudraCT database, and that the member states are required to make some of that information public. EudraCT postings for UK-related studies must continue to be made during the transition period following the UK’s withdrawal from the EU.
Similarly, the advertising code for the pharmaceutical industry published by the Association of the British Pharmaceutical Industry (the ABPI) requires companies to disclose details of clinical trials in accordance with the IFPMA/ EFPIA/PhRMA/JPMA's Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases, and the Joint Position on the Publication of Clinical Trial Results in the Scientific Literature.
There are no particular obligations relating to publication of information on clinical investigations.
There are no restrictions in relation to using online tools to support clinical trials or clinical investigations. However, all advertising of clinical trials and clinical investigations, and all materials provided or directed to subjects, will be reviewed by the relevant ethics committee. There may also be a question as to whether any online tool or application may be considered to be a medical device in its own right, depending on its functionality.
Resulting data from clinical trials is likely to be considered as special category (sensitive) personal data for the purposes of the data protection legislation, even if it is in coded/pseudonymised form. Data collected from patients during clinical trials often relates to their health status, and health data is considered to be special category personal data which is afforded greater protection than non-special category personal data. Where the EU General Data Protection Regulation (GDPR) applies to the processing of personal data (ie, processing is taking place through an establishment in the EU, or in targeting/monitoring individuals in the EU), pseudonymised personal data is still personal data for GDPR purposes, and hence the GDPR needs to be complied with in processing it. The GDPR provides that pseudonymisation is a security measure that can be used to protect personal data, but it does not take the data out of the scope of the GDPR.
The resulting data can be transferred to a third party or affiliate providing that any GDPR provisions governing such a transfer are complied with. For instance, mechanisms may need to be put in place to transfer the data out of the EU, and a contract should be entered into if the third party/affiliate is acting as a processor on behalf of the transferring entity within or outside the EU. The parties also need to comply with the GDPR more generally in respect of the transfer, for instance by ensuring that only necessary and relevant data is transferred, putting sufficient security measures in place in relation to the transfer, and ensuring that the data is only stored for as long as necessary (including to comply with any storage requirements under applicable laws). Moreover, the clinical trial patients must be informed of the identity of the third parties or affiliates who will have access to the personal health data and the purposes for which the data will be transferred to those third parties or affiliates.
During the transition period, EU data protection law continues to apply in the UK and the above will remain valid for the UK.
If the database contains personal or special category (sensitive) personal data, the processing of which the GDPR applies to, the GDPR would need to be complied with. The key requirements would be that the data is processed lawfully (ie, the party managing the database has a lawful basis under the GDPR to collect and store the data); the data stored is relevant, up to date and limited to what is required; sufficient security measures are put in place to protect the data; the data is not stored for longer than is necessary; and the relevant individuals have been informed of the use and storage of their data. The party managing the database would also need to comply with the GDPR more widely, for instance, by following notification requirements in the case of a data breach and having appropriate contracts in place with any third party or parties accessing the database. If the servers hosting the database are located outside the EU (eg, cloud platform), the GDPR rules governing the transfer of personal data out of the EU must also be complied with.
EU data protection law continues to apply in the UK during the transition period and the above will remain valid for the UK at least until 31 December 2020.
Regulation 2 of the Human Medicines Regulations defines a medicinal product as:
Regulation 2(1) of the UK Medical Devices Regulations defines a medical device as any instrument, apparatus, appliance, software, material or other article used alone or combined for humans to:
To distinguish between medical devices and medicinal products, it is important to consider:
The principal intended action of a medical device is typically fulfilled by physical means (including mechanical action, physical barrier, and replacement of, or support to, organs or body functions), whereas the principal action of a medicinal product is normally achieved by pharmacological, immunological or metabolic means. A medical device should not achieve its main intended action by pharmacological, immunological or metabolic means, although it can be assisted by these means.
Where the assessment is not straightforward, or disagreement arises, the MHRA's Medicines Borderline Section is able to issue determinations on whether a product falls within the definition of a medicinal product or a medical device. Its Guidance Note 8 sets out factors that it will consider in determining whether a product should be classified as a medicinal product. These include:
Where doubt remains, the product in question will be classified as a medicinal product.
The Human Medicines Regulations implement EU law regarding the procedures and requirements to obtain an MA. The general rule is that a medicinal product may only be placed on the UK market if it has been granted an MA. Part 5 of the Human Medicines Regulations sets out the details and conditions for an application for grant of an MA in the UK. Setting aside the placing of a centrally approved MA on the UK market, in practice, submissions of MA applications must be made to the MHRA and those submissions that do not meet the relevant requirements will not be validated.
The MHRA may only grant an MA if it is satisfied that:
In an Article 8(3) "full application", this will usually require the submission of substantial manufacturing, pre-clinical (animal) and clinical (from clinical trials in humans) data, known as a full dossier".
Biological medicinal products must meet the same quality, safety and efficacy criteria to obtain MA as non-biological medicinal products. However, since biological medicinal products are especially sensitive to change in starting materials or manufacturing conditions, Annex I to EU Directive 2001/83/EC (the Directive) sets out specific requirements applicable to biological medicinal products.
Certain types of applications can use the abridged application procedure, whereby the application does not need to provide a full dossier, that includes pre-clinical or clinical data, but can cross-refer to data submitted for another medicinal product, known as the reference medicinal product. Abridged applications include the following.
If the new product meets the requirements for a generic product, as defined in Article 10(2)b of the Directive, the application may be abridged to refer to the relevant data of a reference product whose data protection period has expired. Therefore, it can be authorised without its own clinical and pre-clinical data.
A hybrid application can be made for a "variant" of the reference product by complying with Article 10(3) of the Directive. It differs from a generic application in that the results of appropriate pre-clinical tests and clinical trials will be necessary in the following three circumstances: (i) where the strict definition of a generic medicinal product is not met; (ii) where the bio-availability studies cannot be used to demonstrate bio-equivalence; and (iii) where there are changes in the product compared to the reference medicinal product.
A biosimilar application complying with Article 10(4) of the Directive differs from a generic application due to differences relating to raw materials or differences in the manufacturing processes of the biological medicinal product and the reference biological medicinal product. As a result, appropriate pre-clinical tests and clinical trials will be necessary.
The new product may include an active substance which has a well-established medicinal use for a particular indication and an acceptable level of safety such that, consistent with Article 10a of the Directive, the applicant may submit published data demonstrating ten years of systematic use in the EU to support the safety and efficacy of the product.
Consistent with Article 10c of the Directive, a company may provide the "informed consent" of the originator company to rely on its dossier, such that the applicant can get an exact copy of the existing MA.
MAs for medicinal products in the UK are valid for five years. However, an MA ceases to be valid if the product is not placed on the market within three years of the date of authorisation (known as the "sunset" clause).
The renewal application should be submitted to the MHRA six months before expiry. The authorisation may be renewed on the basis of a re-evaluation of the risk-benefit balance. Once renewed, the MA will be valid for an unlimited period unless there are justified grounds relating to pharmacovigilance to proceed with one additional five-year renewal (Regulation 65 of the Human Medicines Regulations).
The MHRA may revoke, vary or suspend a UK MA if any of the 11 conditions listed in Regulation 68 of the Human Medicines Regulations are met. This list of conditions include situations such as the MHRA believing that the product is harmful or that the positive therapeutic effects of the product do not outweigh its risks to the health of patients or the public, or that the product's composition is not as described in the application for the MA or the material supplied with it.
With regards to medical devices, a CE mark is valid indefinitely and the underlying conformity assessment does not require renewal unless the specifications of the device change.
The MHRA has the power to issue:
If the applicant wants to market a medicine only in the UK, an application for a UK national MA must be made to the MHRA. Applicants who have an existing authorisation in another member state can apply under the mutual recognition procedure describing the UK/MHRA as a concerned member state (CMS). There is also the option to start a decentralised procedure at EU level, with the UK/MHRA as a CMS. All applications must follow the Common Technical Document (CTD) format.
The procedure takes up to 210 days (decentralised and national procedures), or 90 days (mutual recognition procedure), excluding time taken to provide further information or if further data or explanations are required. If the UK is a CMS, the MHRA will issue a national licence for the product within 30 days of the close of the co-ordinated procedure.
The current fees range from GBP89,556 for a full application made through the DCP with the UK as CMS, to GBP2,564 for a second-wave mutual recognition application for a simple abridged application. Proof of payment should be included in the application.
The EU Paediatric Regulation 1901/2006 is currently directly applicable in the UK. An applicant in the UK may, therefore, be obliged to conduct paediatric clinical trials or to obtain a waiver or deferral, as necessary, and to provide information regarding existing paediatric studies to the MHRA.
The EU Variations Regulation (EC) 1234/2008 and the provisions of EU Regulation 726/2004 regarding variations to MAs are currently directly applicable in the UK.
Type IA variations can be implemented before the MA holder notifies the MHRA, as long as the MHRA is notified within 12 months. The MHRA will take up to 30 days to process the application. Type IA variations must be notified "immediately" (ie, within two weeks of the change being implemented).
Type IB variations must be approved before they are implemented. The MHRA will assess the application in up to 30 days, and the MAH will be given a further 30 days to respond to any requests for information.
Major, type II variations must be approved before they are implemented. Once the MHRA has all the documents, it will take 30, 90 or 120 days to assess the application, depending on how urgent or complex the changes are, excluding time taken to answer questions.
Fees range from up to GBP25,643 for an extended type II complex variation with the MHRA as the CMS, to no fee for a type IA variation.
The transfer of a granted MA from one legal entity to another is referred to as "change of ownership" in the UK. The legal entity taking over the MA is required to submit an application for change of ownership together with a series of supporting documents (such as letters from the manufacturer(s) confirming that it is prepared to manufacture on behalf of the new MA holder). The application will contain all the necessary particulars of the future MA holder, the existing MA and the new MA holder's declaration of having all the necessary means to comply with the obligations imposed on an MA holder. The application must be signed by the existing MA holder. It is not possible to transfer ownership of pending MAs.
The procedure for a change of ownership is governed by UK secondary legislation and is considered an administrative process. Applications for transfers of ownership attract a fee of GBP442 and take up to 42 days from the date of submission.
In order to obtain a CE mark for a medical device, the manufacturer must follow one of four conformity assessment procedures. The particular procedure will depend upon the classification of the medical device, as the process of conformity assessment is risk-based, having regard to the characteristics of the hazards associated with the device, to minimise harm to users.
For all classes of devices, the manufacturer is required to provide a technical file, although the requirements for the technical file will depend upon the conformity assessment procedure selected. As a general rule, the documentation should cover the design, manufacture and intended operation of the product.
The conformity assessment procedure assesses that a device meets all the general essential requirements and relevant design and construction essential requirements contained in Annex I of the MDD. Where available, relevant harmonised standards may be used to demonstrate how the requirements have been met. The MDD contains no specific requirement to undertake clinical testing, although this is required for certain conformity assessment procedures. However, under the new EU MDRs the evidence required to demonstrate compliance with the general safety and performance requirements has greatly increased. In particular, clinical data is now required.
All but the very lowest risk devices must have a conformity assessment carried out by an NB. The NB ensures manufacturers comply with the requirements, including reviewing clinical and scientific data, manufacturing processes and the quality management system. If they comply, the NB will issue a CE certificate, which manufacturers can use to show that the device has passed the conformity assessment. Low risk Class I medical devices do not need to go through a conformity assessment procedure with an NB. However, they must be registered with the MHRA. For all devices, once the relevant assessment has been successfully completed (and the certificate received, as applicable) the manufacturer may place the CE mark on their medical device and put their device on the UK market.
There are no specific obligations to conduct studies of the use of the medical device in children in order to obtain a CE mark.
If any specification, method of manufacture or intended use of a medical device is amended, it is the responsibility of the manufacturer to ensure that the relevant conformity assessment is updated in order that the CE mark remains a true representation that the product is fit for purpose.
If the ownership of a medical device is transferred to another party, the new party becomes the legal manufacturer and is responsible for the device's compliance with the CE mark. In cases where the medical device is registered with the MHRA, the MHRA should be notified of the new ownership. There is a GBP100 fee for each change request, but it is possible to change more than one detail within each registration request.
With regard to medicinal products, the Human Medicines Regulations state that a person may not 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 an MA. However, consistent with Article 5(1) of the Directive, the UK allows an exception to this provision if:
The supply of unlicensed products under these provisions is often called in the UK "named patient supply", although the patient does not, in fact, have to be named by the doctor seeking supply of the unlicensed product.
The Human Medicines Regulations also set out other exemptions, for example, where medicinal products, other than POMs, are manufactured and assembled in accordance with the instructions from an HCP, or where authorised GSL medicinal products are mixed together, or mixed with a substance which is not a medicinal product, to manufacture a new product. There are also exemptions in relation to advanced therapy medicinal products prepared on a non-routine basis, and for certain radiopharmaceuticals. An MA is also not required where supply is authorised by the MHRA on a temporary basis in response to a suspected or confirmed spread of agents that may cause harm to human beings, such as chemical agents or nuclear radiation. Unlicensed medicines can also be supplied in the context of clinical trials.
When named patient supply of medicinal products is offered to a co-ordinated patient group this is referred to as a "compassionate use scheme". However, the legislative provisions of named patient supply continue to apply.
In 2014, the UK government launched a specific scheme that can give patients access to unlicensed products that have been subject to specified MHRA assessment called, the Early Access to Medicines Scheme (EAMS). EAMS is a voluntary, non-statutory scheme that is intended to run in parallel with the above provisions. The scheme allows patients to access innovative unlicensed medicines earlier than the current MA procedures permit but applies only to medicines that target life-threatening or seriously debilitating conditions for which there are no existing treatments, or where existing treatments are unsatisfactory. There must be sufficient quality, safety and efficacy data available to show that the risk-benefit profile of the product is positive, and that the medicine represents a significant advance in the treatment of an unmet need. Products will normally be eligible for an early access scientific opinion after Phase III clinical trials, although medicines with exceptional and compelling data may be eligible after Phase II. The company that has developed the medicinal product that is subject to the EAMS may not advertise the potential treatment to HCPs, but information is included on the MHRA's website.
Where devices are custom-made for individual patients, or intended for clinical investigation, they do not need a CE mark. Custom-made medical devices are defined by Regulation 5(1) of the UK Medical Devices Regulations as devices manufactured specifically in accordance with a duly qualified medical practitioner's written prescription that gives, under his or her responsibility, specific design characteristics and is intended for the sole use of a particular patient. The manufacturer of a custom-made medical device must meet the requirements of the UK Medical Devices Regulations that relate to custom-made devices.
The MHRA may also approve exceptional use of a non-compliant device on humanitarian grounds under Regulation 12(5) of the UK Medical Devices Regulations. These devices do not need a CE mark. A manufacturer can apply to the MHRA to supply a medical device that does not comply with the law to protect a patient's health if there is no legitimate alternative available. The same provision may be made for custom-made devices that have not complied with the standard conformity assessment procedure.
The MA holder of a medicinal product is responsible for the quality, efficacy and safety of the product throughout the product's life cycle. As part of this, the authorisation holder has an obligation to keep the dossier up to date to take account of scientific and technical progress.
In terms of pharmacovigilance, MA holders are required to operate and audit appropriate pharmacovigilance and risk management systems, to monitor the safety of their products throughout the products' life cycle, and to detect any change to their risk-benefit balance. MA holders must, as part of their pharmacovigilance systems, have an appropriately qualified person responsible for pharmacovigilance located in the EU; maintain a pharmacovigilance master file; operate, monitor and update a risk management system for the product; record and report all suspected adverse reactions occurring in relation to their products; and submit periodic risk-benefit evaluation reports for their products. In addition, they must report any suspected falsified medicines entering the legitimate supply chain (see 3.8 Rules Against Illegal Medicines and/or Medical Devices).
The MHRA may grant an MA subject to one or more conditions, including:
The MA holder must incorporate any such condition into the risk management system for the product.
With regards to medical devices, under the current MDD, and implementing UK Human Medicines Regulations, there are limited post-marketing and vigilance obligations placed on manufacturers within the legislation itself. However, guidance from the European Commission and international standards set out further detail, such as the details of the quality management system that should be in place to demonstrate compliance with the applicable requirements, and the details of the post-marketing surveillance that should be conducted, including monitoring and reporting adverse events, and taking appropriate corrective action. In the UK, the MHRA requires that, once a medical device has been placed on the UK market, the manufacturer monitors and reports to it any serious adverse incidents associated with the product.
Under the new EU MDRs there are enhanced reactive and proactive post-marketing obligations on manufacturers. For example, the legislation now sets out specific requirements whereby, depending on the level of risk that the product poses, manufacturers may be required to: (i) establish and implement a post-marketing surveillance system in a manner proportionate to risk; (ii) develop a post-marketing surveillance plan; (iii) submit periodic safety update reports; and (iv) upon reporting serious incidents, implement field safety corrective action. The EU MDRs also introduce greater visibility over the whole supply chain and requirements relating to traceability of devices. They also introduce enhanced obligations on post-marketing clinical follow-up, whereby the manufacturer must identify potential risks associated with the product as part of the post-marketing surveillance plan and conduct post-marketing clinical follow-up to assess those risks.
Requests for information about MAs and pending MAs for medicinal products may be submitted to the MHRA under the Freedom of Information Act 2000 (FOIA).
The MHRA releases very little information in relation to pending MA applications. Whilst the MHRA will treat requests made under the FOIA on their merits and in accordance with the legislation, the MHRA recognises pharmaceutical companies' commercial interests in limiting the disclosure of information relating to products they plan to bring to market.
Following the grant or the refusal of an MA, the MHRA generally releases detailed information about the application and authorisation, both proactively via disclosures on their websites and also in response to third-party information requests. FOIA provides mechanisms whereby personal data, confidential information and commercially sensitive information may be withheld or redacted from documents requested by third parties, and the MHRA typically allows MA holders to comment on any proposed redactions prior to their release. However, information will be considered commercially confidential in only limited situations where specific and actual evidence is provided to show how disclosure would undermine a company's commercial interests.
With regards to medical devices, the NB registered in the UK (see section 1.2 Regulatory Bodies, above) are private entities. Therefore, access to information provisions that apply to public bodies do not apply. As such, both before and after CE marking, the information pertaining to the device remains the property of the manufacturer. Once registered with the MHRA, a manufacturer's details will be added to the Public Access Database for Medical Device Registration. Records are listed by manufacturer and device and include contact details. Manufacturers of IVDs will not be published on this database, as the IVD Directive contains a confidentiality clause. Other information held by the MHRA could be requested under the FOIA but will only be provided where no exceptions under the FOIA apply.
The European Database for Medical Devices (Eudamed) contains data on medical devices that has been collected and entered by competent authorities and the European Commission. Eudamed includes: (i) data on registration of manufacturers, authorised representatives and devices; (ii) data relating to certificates issued, modified, supplemented, suspended, withdrawn or refused; (iii) data obtained in accordance with the Medical Device Vigilance System; and (iv) data on clinical investigations. Currently, Eudamed can only be accessed by the national competent authorities and the European Commission. However, under the new EU MDRs, parts of the Eudamed database are to be made public. For example, members of the public will be able to access: (i) key information on notified body certificates, suspension, withdrawal and restriction; (ii) clinical investigation reports and summaries; and (iii) field safety notices.
The Falsified Medicines Directive introduced a number of regulatory measures intended to prevent the entry of falsified medicines into the legal supply chain. These measures were transposed through amendments to the Human Medicines Regulations, and include:
The final part of the Directive, the "safety features", Delegated Regulation (EU) 2016/161, came into force on 9 February 2019 and are currently directly applicable in the UK. The Regulation provides for a requirement for POMs to include certain safety features, including a seal on the outer packaging (to indicate whether the pack has been tampered with) and a unique identifier.
The MHRA has enforcement powers under the UK Medical Devices Regulations and the General Product Safety Regulations 2005 (SI 2005 No 1803). As part of this, the MHRA can investigate any business activity that is covered by those regulations, which includes falsification and illegal distribution of medical devices. To ensure that medical devices placed on the market and put into service in the UK meet these regulatory requirements, the MHRA assesses all allegations of non-compliance raised using a risk-based system, monitors the activity of the NB designated by MHRA to assess the compliance of manufacturers, investigates medical devices as a result of adverse incident reports or intelligence indicating a potential problem, and carries out proactive risk-based projects with other member states to identify emerging risks. These activities currently form part of the MHRA's market surveillance obligations under EU law and are intended to capture, amongst other things, falsified and legally non-compliant devices.
There are a number of options for using IP rights to tackle counterfeit pharmaceuticals and medical devices at the UK border, which are discussed below in 11 IP Other Than Patents. Counterfeit medicinal products and medical devices can be detained by the UK customs authority, the UK Border Agency (UKBA), on entry into the UK. Under Regulation 608/2013 (the Customs Regulation) the holder of an IP right, including a patent or a trade mark, can register its right with the UKBA and ask the UKBA to detain goods that are suspected of infringing that right.
A manufacturer licence issued by the MHRA is required in order to manufacture medicinal products. The process involves submission of an application. Thereafter, the MHRA will inspect the designated manufacturing site to verify compliance with GMP. Applications are generally processed within 90 working days. Depending on the type of licence, they entitle the holder to manufacture, assemble or import licensed, unlicensed or investigational medicinal products. A manufacturer licence remains in force until it is revoked by the MHRA or it is surrendered by the licence holder.
Manufacturers of medical devices are not required to obtain a specific authorisation. Depending on the classification of the medical device, the manufacturer may be required to register with the MHRA or be assessed by an NB in order to place the medical devices on the market in the UK.
During the transition period, while the UK is no longer a member of the EU, it will continue to be subject to EU rules and remain a member of the single market and customs union. Accordingly, UK-granted licences for manufacture and distribution will continue to be mutually recognised by the EU. The transition period seeks to secure frictionless trade between the UK and the EU while the future trading relationship and security co-operation are negotiated.
A wholesale distribution authorisation issued by the MHRA is required in order to engage in the sale, supply, or offer for sale or supply of POMs, pharmacy, traditional herbal and GSL medicines in the UK, or to import licensed and unlicensed medicinal products into the UK from countries inside the EEA.
As with manufacturer licences, applications are generally processed within 90 working days. The facility involved in wholesale distribution is subject to inspection by the MHRA before a licence is granted. A wholesale distribution authorisation remains in force until it is revoked by the MHRA or it is surrendered by the authorisation holder.
Distributors of medical devices are not required to obtain an authorisation to engage in wholesale trade.
The Withdrawal Agreement, provides that medicinal products and medical devices lawfully placed on the market in the EU or UK before the end of the transition period can continue to circulate between the UK and the EU as a single market. This transition arrangement applies to all goods that have been fully manufactured and are the subject of an offer or agreement for the transfer of ownership, property right or possession, before expiry of the transition period. In order to benefit from this transition arrangement, companies are required to document and retain evidence of any agreements and offers made.
As mentioned in detail in 1.3 Different Categories, medicinal products are classified within three categories:
Importing and exporting medicinal products is governed by the Human Medicines Regulations 2012. Importing medical devices is governed by the UK Medical Devices Regulations 2002 and, when coming into operation, the EU MDR and the EU IVDR. There are no specific rules regarding exporting medical devices.
HM Revenue and Customs is responsible for border control. The MHRA Enforcement Group is responsible for applying and enforcing the Human Medicines Regulations and the UK Medical Devices Regulations.
Import requirements depend on whether the goods are imported from countries within or outside the EU. As, at the date of writing, most goods imported from other EU countries circulate freely on the EU single market and so can be imported with minimal customs control and no import duty or VAT to pay. This position may change following the expiry of the transitional period. Importers of goods from outside the EU must make an import declaration to customs and will generally have to pay import duty and import VAT.
Businesses that are established in the EU, actively involved in customs operations and international trade and have an Economic Operator Registration and Identification (EORI) number can register with HM Revenue and Customs (HMRC) as Authorised Economic Operators. The scheme is not compulsory, but companies that meet the requirements can take advantage of simplified customs procedures for the security and safety of their imported goods in transit. Note that the designation of a particular entity as the importer of record for customs purposes will not be conclusive in determining who should hold any required import authorisations from a regulatory perspective.
Medicines authorised in both the UK and another EU member state may be parallel imported from that other member state and marketed in the UK, provided the imported product has no therapeutic difference from the corresponding UK product. Parallel importers must submit an application to the MHRA for a Parallel Import Licence prior to any importation. They must also hold a wholesale distribution authorisation covering importing, storage and sale of the relevant products. Any relabelling or repackaging activities will likely require a manufacturer licence. Medicines that are unlicensed in the UK can be imported and used to meet the special clinical needs of a patient that cannot be met by a licensed medicine. Parallel distributors wishing to market, in the UK, a centrally authorised product originally placed on the market in an EU member state must currently notify the EMA.
No authorisation is required to import medicines into the UK where that import is strictly for use by the importer or a member of their immediate family. Personal use is viewed as up to a three-month supply, with no onward sale or supply.
Importers of medical devices from outside the EU are not required to obtain an import authorisation but will instead become legally responsible under the medical devices legislation for those devices. They may choose either to sell under the name of the actual manufacturer as its local authorised representative, or to sell under the importer’s name (but will then require an agreement with the actual manufacturer to ensure access to the technical documentation relating to the CE marking).
A common customs tariff is currently charged across all EU countries on goods imported from outside the EU. Details of specific tariff duties and measures that apply to particular goods in the UK are contained in the Integrated Tariff of the UK. An importer or exporter is responsible for the correct tariff classification of goods. HMRC has developed an online trade tariff tool to assist in product classification.
During the transition period the UK continues to benefit from the free trade arrangements of the EU and European Free Trade Association (EFTA). It also remains a member of the World Trade Organization (WTO).
Statutory controls on pharmaceutical pricing are set out in the National Health Service Act 2006 (as amended) and subordinate legislation. Products that are not supplied through the National Health Service (NHS) are not subject to price controls; in practice, though, over 90% of medicines are supplied through the NHS.
The 2019 voluntary scheme for branded medicines pricing and access (VPAS) – a voluntary agreement negotiated between the Department of Health and the Association of the British Pharmaceutical Industry (ABPI) – controls prices of branded medicinal products indirectly by controlling profit on NHS business, and by establishing a budget cap on the total expenditure by the NHS on branded health service medicines, with member companies making scheme payments to the Department of Health (calculated as a percentage of eligible net sales) as quarterly rebates to cover excess expenditure. The payment percentage for 2019 under the VPAS was 9.6% and for 2020 is 5.9%. The VPAS is an agreement which is not binding under the law of contract; however, the Secretary of State may enforce sums payable under the Scheme, using powers under Section 261(9) National Health Service Act 2006.
New branded health services medicines which contain a new active substances and are supplied by VPAS member companies are subject to free pricing at launch, as are line extensions of such medicinal products launched within 36 months of licensing of the initial indication in the UK; the prices of such products must, however, be notified to the Department of Health prior to launch. The price for all other branded health service medicines supplied by VPAS member companies must be agreed with the Department of Health. There is no formal system of international reference pricing, although the cost of the presentation in other markets is specifically listed as a relevant criterion to which the Department of Health should have regard.
If a company is not a member of the pharmaceutical pricing regulation scheme (PPRS) (around 10% of companies), it is regulated by the parallel Statutory Scheme, currently set out in the Branded Health Service Medicines (Costs) Regulations 2018 (as amended). The Statutory Scheme is applicable only to branded health service POMs. From 1 April 2018, it has involved a payment scheme, calculated as a percentage of net sales, similar to the scheme payments required under the VPAS. Payments are made on a quarterly basis; the payment percentage is currently 9.9%, however the Secretary of State proposes to reduce the payment percentage from 1 April 2020 to 7.4% so that there continues to be broad commercial equivalence with the Voluntary Scheme. The maximum price which may be charged for a branded health service medicine within the Statutory Scheme is that directed by the Secretary of State. The Scheme includes a requirement to pay interest where payments are made late and daily penalties may additionally be imposed.
In primary care, the price of some medicinal products is also indirectly controlled by the reimbursement price, as set out in the Drug Tariff (a monthly publication, specifying the amounts to be paid to contractors for providing relevant services). These prices are calculated based on sales information provided by pharmacies, manufacturers and wholesalers. Where the Drug Tariff does not list a reimbursement price for a particular medicinal product, which is the situation for most originator products prior to patent expiry, or where a product is prescribed by brand name, it will be reimbursed at the manufacturer's NHS list price.
Medical devices will only be routinely dispensed in primary care through the NHS if they are included in the Drug Tariff. The Department of Health/NHS Business Services Authority (NHSBSA) agrees the reimbursement price of the medical device with the device manufacturer at launch. The reimbursement price will principally be determined by comparing the device with similar products on the market and their respective prices. If there are no comparable devices or the applicant submits evidence to support a different price, the reimbursement price is determined by negotiation between the parties. The sale of any device not listed within the Drug Tariff is a matter for negotiation between the seller and the local NHS.
All medicines validly prescribed on an NHS prescription may in principle be reimbursed from public funds, unless expressly excluded. Schedules 1 and 2 to the National Health Service (General Medical Services Contracts) (Prescription of Drugs, etc) Regulations 2004 list a limited number of products that:
In primary care, patients receive medicines prescribed by their general practitioners from pharmacies in the community. Patients in England must pay a fixed price for NHS prescriptions, unless they fall within one of a number of exempt categories (for example, children, the elderly and persons suffering from certain chronic diseases); the current prescription charge (as from 1 April 2019) is GBP9. Prescription charges have been abolished in Northern Ireland, Scotland and Wales.
In relation to reimbursement of medicinal products used in NHS hospitals, the Health and Social Care Act 2012 established the "national tariff" – a set of prices for defined items of care (currencies). Hospitals are paid by commissioners, based on procedures performed or care provided, with the cost of the procedure or care (including the costs of associated medicines and devices) fixed in the national tariff. Certain high-cost medicinal products and medical devices are reimbursed outside the tariff system and enhanced payments may be made for some patients.
When a medicinal product receives an MA, the NHS list price must be notified or agreed (as appropriate) with the Department of Health before it is supplied to the NHS. All such products may, in principle, be reimbursed without further cost-benefit analysis.
However, in England most new medicines (and new indications for existing products) undergo health technology appraisal by the National Institute for Health and Care Excellence (NICE), which issues guidance to the NHS on use of the particular medicinal product, based on an assessment of clinical effectiveness and cost-effectiveness relative to alternative therapies. NHS bodies in England are required by regulations to make funding available so that patients are able to access treatments recommended by NICE in technology appraisal guidance, generally from a date three months after guidance is issued. In cases where the estimated budget impact associated with use of the technology exceeds GBP20 million in any of the first three years after launch, NHS England may ask NICE to delay the period for mandatory implementation.
NICE also assesses some medical devices and diagnostic tests through parallel procedures.
The All Wales Medicines Strategy Group (AWMSG) issues guidance on new technologies immediately following launch, prior to NICE guidance being issued or where NICE will not be conducting an appraisal. In Scotland, the Scottish Medicines Consortium (SMC) assesses all new medicines and new indications for existing medicines and issues guidance close to the product launch. In Northern Ireland, the Department of Health, Social Services and Public Safety considers NICE guidance and reviews it for legal, policy and financial consequences only, before deciding on implementation.
While theoretically NHS prescribers may prescribe any product they consider to be clinically appropriate for their patients, in practice NHS commissioners control which medicines may be prescribed through local or national formularies, the content of which is largely determined by the cost-effectiveness of individual products. Treatments recommended by NICE should be included automatically in NHS formularies in England. In contrast, products which are not recommended by NICE are generally not funded on a routine basis. An equivalent approach is taken to products recommended by the AWMSG, the SMC and the Northern Ireland Department of Health, Social Services and Public Safety in the devolved administrations.
In addition to NICE's recommendations (or those of the AWMSG, the SMC and the Northern Ireland Department of Health, Social Services and Public Safety) the following factors will be used to determine whether medicines are funded:
Community pharmacists purchase products from manufacturers or wholesalers and are reimbursed by the NHSBSA for the service they provide and the products they dispense at the rate specified in the Drug Tariff, or, where no reimbursement price is set in the Drug Tariff, at the manufacturer's list price. To the extent that the price paid by the pharmacist is less than that reimbursed by NHSBSA, the pharmacist makes a margin of profit. The extent of this margin is monitored by NHSBSA and clawbacks are imposed to ensure that pharmacy profits do not exceed defined limits.
There is no generic substitution by community pharmacists in the UK and the Medicines Act 1968 requires the particular product prescribed in a prescription to be dispensed. However, in general, doctors are encouraged to prescribe products using their international non-proprietary name (INN) and NHS prescribing systems convert prescriptions for a branded product to the INN, unless the doctor specifies otherwise. Where a product is prescribed by its INN, the pharmacist may dispense any product that meets the specifications/INN described and is likely to select the lowest-cost product. Generic substitution is standard practice in the hospital context.
There are no specific rules governing medical apps in the UK. Standalone software and medical apps that meet the definition of a medical device (set out in section 1 Regulatory Framework, above) will be regulated as medical devices and are required to be CE marked. Not all apps used in a healthcare setting will be medical devices. A case-by-case assessment is required considering the product's functionality as a whole. One of the key factors to determine whether stand-alone software or an app falls within the definition of "medical device" is whether its use has a medical purpose. Under the current MDD, the default classification for apps that are medical devices is Class I. Under the EU MDR, many such apps will instead be classified as Class IIa or IIb. This will require the involvement of an NB. The EU MDR will also require the manufacturer to produce more clinical evidence than under the current regime.
Physicians can, and do, provide medical attention remotely in the UK, including through mobile devices. However, there are currently no specific and separate rules for telemedicine. Under English law, the provision of telemedicine services constitutes the provision of healthcare, which is a regulated activity under the Health and Social Care Act 2008 (Regulated Activities) Regulations 2014, subject to the supervision of the Care Quality Commission (CQC), the independent regulator of health and social care services in England. In order to provide healthcare services in England, providers must be registered with the CQC, and must demonstrate that the care and treatment they provide meet the requirements of the Health and Social Care Act 2008, and its associated regulations. The CQC is responsible for all health and social care provision in England, regardless of whether it is provided remotely or face-to-face, and the same standards apply in either case.
The practice of medicine is regulated separately by the General Medical Council (GMC), the regulatory body for doctors, which is responsible for giving advice on standards of professional conduct and medical ethics. In order to practise medicine in the UK, doctors are required to be registered with the GMC, to hold a licence to practise and to revalidate that licence on a five-yearly basis. As with the CQC's regulation of healthcare providers, the same standards apply to doctors, regardless of whether they practise in physical or virtual clinics.
There are no special legal provisions applicable to the online advertising and promotion of medicines and medical devices. Pharmaceutical and medical technology companies may use online portals, web pages and social networking sites to promote their products, provided they follow the applicable UK medicines advertising legislation and the medical devices legislation (which implement the existing EU rules), guidance and codes of practice. Breaches of these requirements through online activities are enforced in the same way as activities involving traditional methods of communication.
In practice, pharmaceutical companies rely on the guidance provided by the MHRA and, under the self-regulatory system, the Prescription Medicines Code of Practice Authority (PMCPA) and the Proprietary Association of Great Britain (PAGB).
The MHRA Blue Guide confirms that material posted on UK websites (including social networking sites, blogs and discussion forums) and/or aimed at a UK audience is subject to UK medicines advertising legislation.
Clause 28 of the ABPI Code, which is controlled by the PMCPA, deals with online advertising and promotion, and states that promotional material about prescription-only medicines directed to a UK audience that is provided on the internet must comply with all relevant requirements of the Code.
In addition, the PMCPA has published guidance on digital communications, which includes advice on how companies can make the best use of digital communication tools such as Twitter, Facebook, Pinterest and Wikipedia, whilst complying with the restrictions under the ABPI Code. This guidance makes clear that companies should be able to use any method of communication to provide materials to any audience. However, such communication must follow the requirements of the ABPI Code, in particular in relation to prescription-only medicines.
The PAGB Consumer Code for Medicines provides a section on the internet advertising of medicines purchased over-the-counter (OTC), and states that all web-based promotional materials, over which companies have full editorial control, must comply with the Code and, like other forms of advertising of OTC medicines to members of the public, must be submitted to PAGB for approval (in an offline format). This requirement includes brand websites, social medial sites, pay-per-click advertising, banner ads and press releases for Internet publication. However, Facebook and Twitter posts which do not mention the product and do not contain any direct or implied claims, or any references to, the therapeutic category do not require advance approval by PAGB. User-generated reviews on brand websites are not covered by the PAGB Code unless adopted or incorporated by the company.
The self-regulatory regime for the medical technology or devices sector is primarily controlled by the Association of British Healthcare Industries (ABHI) in accordance with the principles set out in its Code of Business Practice, which requires any advertising of medical devices to be accurate, balanced, fair, objective and unambiguous. The ABHI Code, does not provide specific rules to online advertising of medical devices but covers it in the same manner as other forms of advertising. The web-based promotion of self-care medical devices is subject to the PAGB Medical Devices Consumer Code.
Electronic prescription is permitted in the UK, provided the prescription is created electronically, signed with an advanced electronic signature and sent to the person by whom it is dispensed as an electronic communication. If the prescription is for a substance or product listed in Schedule 2 or 3 of the Misuse of Drugs Regulations 2001 (excluding oral liquid methadone), it must be sent to the person by whom it is dispensed via the electronic prescription service managed by the Health and Social Care Information Centre, the UK's national provider of information, data and IT systems for the NHS, which is more commonly known as NHS Digital. In addition, electronic prescriptions must comply with all the general requirements for prescriptions, including those relating to the particulars required to be stated (ie, date, details of the patient and the prescribing clinician).
Online sales of both medicinal products and medical devices are permitted in the UK.
With regard to medicinal products, any person based in the UK offering medicines for sale to the public in the UK (or in another EEA country) via a website, must be registered with the MHRA and be included in its list of UK-registered online retail sellers. Once registered with the MHRA, the seller must clearly display – in a visible position on every page of its website that offers to sell medicinal products to the public – the EU Common Logo (the EU distance selling logo, intended to help members of the public identify websites that can legally sell medicinal products to the public). The website must also contain the contact details of the MHRA and a link to the MHRA website.
Medicines classified as P or POMs can only be supplied at a registered pharmacy, under the supervision of a pharmacist, even when the sale or supply is made online. All pharmacies in Great Britain, including those providing internet services, must be registered with the General Pharmaceutical Council (GPC). A registered pharmacy that offers to sell or supply medicines to patients and the public over the internet can apply to the GPC for permission to display the voluntary internet pharmacy logo on its website. This is separate from the EU Common Logo and is intended to provide reassurance to patients and the public that they are purchasing medicines online from a registered pharmacy that meets the GPC standards for registration.
As regards medical devices, there are no specific requirements for online selling. However, as explained above, in order to place medical devices on the market in the EU, a manufacturer (or its authorised representative), must complete a conformity assessment in order to place the CE mark on its products, and register with the MHRA.
In addition, a person selling medicines or devices online must comply with a number of other requirements, such as:
Website operators may also have to provide information relating to IP rights, a slavery and human trafficking statement (if the company's global turnover is GBP36 million or more) and, if website operators are processing the personal data of users, information to users as required under applicable data protection laws. The European General Data Protection Regulation (2016/679) sets out a list of information to be provided to individuals in such circumstances, and the UK Privacy and Electronic Communications (EC Directive) Regulations 2003 govern cookies and electronic direct marketing.
Electronic health records are regulated in the UK, particularly under data protection laws. Health data is considered to be “special category” personal data under the GDPR, which means that there are stricter conditions for processing it. For instance, parties processing health data need to ensure that they have an appropriate legal basis to process that data, such as the processing being necessary for the provision of medical care, reasons of substantial public interest, or scientific research. Data protection breaches involving special category personal data can also attract more severe penalties (depending on various factors, including the nature of the breach and number of individuals affected).
Where the processing of special category (or other) personal data is subject to the GDPR, and that data is transferred to a cloud platform, the transferring entity and the cloud platform would need to comply with the GDPR. A contract should be entered into between the parties setting out the responsibilities of each under the GDPR. The requirements under the GDPR for transferring personal data out of the EU would also need to be complied with. The parties should ensure that the data being transferred and stored is protected using appropriate security measures (such as pseudonymisation/password protection), and that the relevant individuals have been notified of the collection and storage of their data. In addition, electronic-health-records software tools used in the conduct of clinical trials must be validated for compliance with GCP and for use in accordance with the specific protocol for the clinical trial.
During the transition period, EU data protection law and EU law governing the conduct of clinical trials continue to apply in the UK. The above position will, therefore, remain valid for the UK.
Licensing transactions in the pharmaceutical and biotech sectors typically involve more milestone value than transactions in the medical device sector, and considerably more than most other sectors. Deal structures are driven by the type of product involved and its stage of development. Licences of complex early stage products, such as cell and gene therapies, tend to involve more innovative partnering and collaboration arrangements, reflecting the challenges in developing these products and the fact that few companies have the ability to bring them to market single-handed. For early stage products, the triggers for payment of milestones will commonly be study results, the achievement of specified regulatory filings or approvals, grant of MAs and achieving first sales. For later stage products, payments tend to be linked to net sales.
Dispute resolution provisions in licence agreements are typically multi layered, involving escalation to various levels of management within each party before litigation or arbitration is triggered. The parties may include an option to attempt mediation before doing so, and purely technical disputes – such as whether a product complies with specifications or how net sales have been calculated – are often carved out of this process and, instead, referred to independent experts for determination.
Diligence obligations are typically defined by reference to "commercially reasonable efforts". Whilst there is a considerable body of English case law discussing the meaning of this term, the decisions are all highly fact-specific and so the parties to licence agreements will frequently seek to define this term based on their individual circumstances. This definition will either set an objective standard, based on the efforts that a company with similar products at a similar stage of development or commercialisation would reasonably be expected to employ, or (often for larger entities) a subjective standard based on the efforts that the company in question typically employs for similar products.
Licensees may seek to include a termination right in the event of a change of control, failing which they will typically require the ability to step in and maintain or enforce any IP if the new licensor fails to do so. Licensees will often register their interest on relevant IP registries to ensure that any subsequent owner is aware of the licence.
Licensors often have a stronger argument for including a right to terminate on a change of control, to protect against having to continue the licence with an unwanted counterparty. Licensees will typically argue that this should not restrict their ability to undergo corporate restructurings, IPOs or other exits.
Upon termination of a licence agreement, the licensee’s right to continue to exploit or use the relevant licensed IP will cease, and any sublicences granted by the licensee will terminate. The agreement should address the immediate practical steps to be followed, such as the return of stocks of licensed products and confidential materials. The licensor’s ability to use clinical data, or other IP generated by the licensee, post termination will turn on the terms agreed between the parties as to ownership and licensing of IP and data arising during the course of the agreement, and will often vary depending on the basis for termination. As the licensor will likely want to continue to exploit the licensed IP it will usually require at least access to (if not ownership of) data generated by the licensee, any improvements it has generated and any regulatory approvals applied for or granted in the course of the licence. However, blanket assignments of arising IP back to the licensor may be problematic from a competition law perspective.
UK patent law is governed by the Patents Act 1977, as amended, (the Patents Act) as interpreted by binding judicial precedents.
The UK is a signatory to the Patent Co-operation Treaty 1970 (PCT) administered by the World IP Office and the European Patent Convention 2000 (EPC 2000). The PCT provides a single route for filing a patent application in all of the contracting countries, but examination and grant of patents are dealt with by national or regional patent offices. The EPC 2000 provides a single route for the examination and grant of a patent across all contracting European states via the European Patent Office, although once granted a European patent operates as a bundle of individual national patents.
The UK is a signatory to the Unified Patent Court Agreement (UPCA) which, together with the associated EU regulations establishing the Unitary Patent, provides for the grant and enforcement of a single unitary patent across all participating EU member states.
However, at the end of February 2020, the UK government has confirmed that the UK will not seek to participate in the UPC system. This decision will not prevent UK companies from being able to litigate before the UPC, and the UK’s non-participation in the UPC does not affect the UK’s ongoing participation in the European Patent Convention or the fact that European patents will still be available to register in the UK. Lastly, supplementary protection certificates (SPCs) and paediatric extensions are governed by EU law, as discussed further below.
Infringement and validity claims form the bulk of the cases issued before the UK courts concerning pharmaceutical patents and SPCs. The increasing amount of data required to be disclosed is a challenge for the grant of pharmaceutical and biotech patent inventions, particularly in relation to second or further medical uses.
An invention (pharmaceutical or otherwise) is patentable if it: (i) is new; (ii) involves an inventive step; (iii) is capable of industrial application (a fairly low hurdle); and (iv) is not specifically excluded from patent protection. A number of exclusions to patentability relate exclusively to pharmaceutical or biotech inventions (eg, methods of treatment by surgery or therapy, methods of diagnosis, and uses of human embryos for industrial or commercial purposes).
Claims to second and subsequent medical uses, including in relation to dosage regimes and new or selected patient populations, are patentable as long as:
However, the patent applications may be subject to higher hurdles regarding the experimental data required to support claims of such second and subsequent medical use.
The Supreme Court, in the Warner-Lambert v Mylan & Actavis case concerning the drug pregabalin, provided obiter guidance on infringement. In relation to direct infringement (ie, disposal/offering to dispose/use/importation of a product obtained directly by means of the patented process) and whether the intention of the manufacturer was that the product should be used for the patented purposes, the majority view from the Supreme Court was to apply an "outward presentation" test, in which the objective characteristics of the product in question ought to be considered with regard to the way it is packaged and marketed. In this view, if a product does not make clear its use is limited, it will infringe. In relation to indirect infringement, the Supreme Court unanimously rejected the idea that a Swiss-type claim could be indirectly infringed.
Patent term extensions in the UK are in the form of the Supplementary Protection Certificate (SPC), an EU sui generis right governed by EU Regulation 469/2009 (the SPC Regulation) and Regulation 1901/2006 (the Paediatric Regulation). The Patents (Amendment) (EU Exit) Regulations 2019 will come into effect at the end of the transition period. These regulations will bring current EU legislation into UK law as far as possible, to maintain current systems and processes.
The SPC Regulation provides for a patent's term to be extended for a period equal to the period between the date of filing of the patent and the date of grant of the first authorisation to place the product on the market in the EU, less five years. The extension is subject to a maximum duration of five years. The Paediatric Regulation provides for an additional six-month extension of term if the patent holder completes an agreed Paediatric Investigation Plan to determine whether the product is safe for use in children.
On 1 July 2019, Regulation (EU) 2019/933 came into force and amended the SPC Regulation to allow generic companies to seek an SPC waiver to: (i) export medicines protected by an SPC to markets outside the EEA; and/or (ii) make and stockpile medicines protected by an SPC during the last six months before the expiry of that SPC, for launch in the market in EEEA on day one of SPC expiry.
SPCs can be challenged by third parties who may bring a revocation action in the UK courts.
Despite a significant number of preliminary references to the CJEU seeking guidance as to the interpretation of the SPC Regulation, there is still uncertainty over the conditions for obtaining an SPC including: (i) what is meant by “protected by the basic patent in force” in the context of functional or Markush claims; and (ii) can a patentee validly seek an SPC in relation to a product covered by its patent where an unconnected third party is the owner of the MA covering that product?
Where a patent covers a pharmaceutical product or medical device, it is an infringing act to make, sell, offer to sell, use, import or keep the product or device in the UK. It is not an infringing act to make an offer to sell a product before patent expiry if the offer is to sell the product after patent expiry. It is also not an infringing act to merely apply for, or obtain, authorisation to sell a pharmaceutical product or medical device before patent expiry.
Where a patent covers a method for making a pharmaceutical product or medical device, it is an infringing act to use the patented method in the UK. It is also an infringing act to sell, offer to sell, use, import or keep a product "obtained directly" by means of the patented process. Whether a product has been "obtained directly" from a patented process is a question of fact in each case and has been the subject of a number of disputes in the UK.
It is also an (indirect) infringement to supply, or offer to supply, in the UK means relating to an essential element of the invention, for putting the invention into effect, knowing (or it being obvious to a reasonable person in the circumstances) that those means are suitable for putting, and are intended to put, the invention into effect in the UK.
It is possible to apply for an injunction restraining a party from infringing a patent on the basis of a threat of infringement, even if no actual infringement has occurred. There is no requirement that the infringement be "imminent" in order for an injunction to be granted; the patent-holder only needs to prove that there is a sufficiently strong probability that, in the absence of an injunction, the other party will infringe the patent.
There are a number of general exemptions from patent infringement which might apply to pharmaceutical products and medical devices:
A compulsory licence of a UK patent is available if, where the patented invention is a product, demand for that product is not being met on reasonable terms. A compulsory licence is also available if the patent-holder's behaviour is causing the establishment or development of commercial or industrial activities in the UK to be unfairly prejudiced, or if the exploitation of an important technical advance of considerable economic significance is being hindered. These compulsory licence provisions are rarely asserted and are therefore of limited relevance in practice. However, there have been an increasing number of cases where the patentee does not seek an injunction provided an appropriate royalty is agreed or awarded by the court for future infringement, in effect a court-imposed compulsory licence following a finding of infringement.
An action for infringement may be brought by the patent-holder or by an exclusive licensee.
The remedies available for infringement are an injunction to prevent future infringement, damages or – at the discretion of the patent-holder – an account of the infringer's profits.
The patent-holder may also seek delivery or destruction of all infringing articles in the possession or power of the infringer.
An action for infringement can be brought in the Patents Court or in the IP Enterprise Court (IPEC), both of these courts being part of the English High Court.
The IPEC is designed to deal with lower-value, less complex cases. The IPEC multi-track is most relevant to the life sciences sector with a limit on damages of up to GBP500,000, and costs recovery subject to a GBP50,000 cap.
Higher-value claims must be brought in the Patents Court. Depending on the parties' assessment of the technical complexity of the case, the case may be heard by a specialist patents judge.
An infringement action is commenced with the issue of a claim form and particulars of claim, outlining the patent-holder's claim for infringement. The alleged infringer then submits its defence and any counterclaim, which may include a counterclaim for invalidity. If the alleged infringer raises a counterclaim, then the patent-holder will serve its own defence. Parties may then reply to any defences. Following the exchange of formal pleadings, the court will schedule a case management conference to set the timetable for the action and the estimated trial date.
From 1 January 2019, a two-year mandatory disclosure pilot scheme has been operating. For patent cases, for which disclosure was already limited, the effect of this scheme has, arguably, been to create a greater administrative burden on parties and not necessarily manage costs. The alleged infringer may still submit a product or process description to avoid giving disclosure in relation to infringement.
Expert evidence is typically exchanged before trial in written witness statements, and the experts are cross-examined on the content of these statements during the trial. The parties may, if necessary, also provide evidence of experiments relating to infringement or validity, subject to a tightly controlled procedure.
The procedure in the IPEC is more streamlined in order to keep costs in proportion to the value of the claim, and the judge has wide case management powers to achieve this. Similar, but not identical, procedures are being trialled in the Patents Court which may provide something of a halfway house.
Invalidity is available as a defence to an infringement claim and is raised by way of a counterclaim. If validity is challenged then the alleged infringer is required to serve "grounds of invalidity" setting out on what basis the patent is said to be invalid, including any prior art cited in support of a lack-of-novelty or obviousness attack.
There is no requirement for prelaunch declaratory actions by a generic entrant. There is no patent linkage between the authorisation for a pharmaceutical product and the patent position (unlike the position in the USA). However, a generic entrant who does not clear the way risks facing infringement claims or injunction applications by patent-holders and this may prevent the launch of the product.
A generic entrant who wishes to clear the way may start an action to revoke a patent or SPC. Alternatively, or in addition, the generic entrant may seek declaratory relief from the UK Courts:
A rights-holder has a number of options for tackling counterfeit pharmaceuticals and medical devices, such as trade mark infringement, patent infringement, copyright infringement or passing off.
A trade mark infringement action is typically more straightforward than a patent infringement action and generally the action of choice where counterfeit pharmaceuticals and medical devices are concerned. Trade-mark infringement carries both civil and criminal liabilities under the UK Trade Marks Act 1994. It is possible to bring a private criminal prosecution against an infringer, although criminal proceedings are more usually brought by the UK's Trading Standards Authorities or by the MHRA. In addition, the MHRA has the power to bring criminal proceedings against counterfeiters under the Human Medicines Regulation. Civil proceedings may be appropriate when dealing with counterfeiting on a large scale, or where the rights-holder wishes to take advantage of the procedural tools and remedies offered in civil proceedings (for example, search orders or injunctions).
Counterfeit goods may be subject to border seizure actions. The HMRC, together with Border Force, are responsible for preventing counterfeit goods entering the UK. Under EU Regulation 608/2013, the holder of an IP right can register its right with the UK Border Agency to detain goods which are suspected of infringing that right. Rights holders can send a rights application for action (AFA) to HMRC to get Customs action, either by way of a National AFA for Customs action at the UK borders only, or a Union AFA for Customs action in two or more EU member states.
During the transition period, a Union AFA submitted to or granted by Customs in one of the EU member states will remain valid, even if it also designates the UK. Once the transition period is over, and subject to further transitional arrangements agreed between the UK and the EU, it will not be possible to submit Union AFAs to UK Customs and any existing Union AFAs designating the UK will become ineffective.
For medicinal products, under the centralised procedure, the EMA will authorise a product name. Otherwise than in exceptional cases (eg, where the proposed trade mark has been cancelled, opposed or objected to under trade mark law in a member state) a single name must be used throughout the EU.
The EMA has issued guidelines on the acceptability of names or human medicinal products. The requirements include that the invented name of a medicinal product should not:
The usual rules in relation to registration of any trade marks also apply, although the EMA will not take into consideration aspects of IP rights/trade mark registration within its review.
The MHRA's guidelines on appropriate trade marks for medicinal products are much the same as the EMA's guidance, although traditionally the UK has shown more flexibility where a business reason for a particular name does not have manifest public health implications.
The UK Medical Devices Regulations does not contain any restrictions on the product names or trade marks of medical devices. However, as with any trade mark for a medical device in any EU country, names/signs which:
should be avoided.
The EU MDR and the EU IVDR entered into force on 25 May 2017. However, these Regulations will not apply fully until after the transition period has ended, on 25 May 2020 and 2022 respectively. During the transition period, devices can be placed on the UK market under the current MDDs, or the new EU MDRs (if they fully comply with their provisions). Article 7 of the EU MDR and the EU IVDR include a new requirement concerning claims. In particular, trade marks used in connection with the labelling, instructions for use, making available, putting into service or advertising of a medical device are prohibited if they may mislead the user or the patient with regard to the device's intended purpose, safety and performance by:
IP protection is available for the trade dress and design of pharmaceuticals, medical devices and their packaging. The packaging of a product, the precise design of a tablet or the design of a medical device may potentially be protected by copyright, registered or unregistered design rights, and sometimes by trade marks. The applicability and extent of such protection will depend on whether the trade dress or design in question meets the criteria for such protection. In addition, medicinal products or medical devices may be protected by a right in the tort of passing off, which protects the goodwill associated with those products.
Innovator pharmaceutical companies benefit from a period of regulatory data protection and marketing protection to protect the investment made in developing a medicinal product. The regulatory data protection period is eight years, during which a generic applicant cannot cross-refer to the innovator's pre-clinical and clinical data to obtain an MA for a copy product. In addition, the marketing protection period is a further period of two years (making a total of ten years) during which a copy product that is authorised based on the innovator's pre-clinical and clinical data cannot be placed on the market. This combined period of eight-plus-two years is often known as the data/marketing exclusivity period. There is also the possibility of extending this period by an additional year in certain circumstances, such as on the approval of a new indication bringing significant clinical benefit when compared with existing therapies.
There are no regulatory protection periods or exclusivities for medical devices.