The Pharma Legal Handbook: United Kingdom

Want to know more about regulatory reforms in United Kingdom? Read on! Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. Are there proposals for reform or significant change to the healthcare system?

The UK is currently due to leave the EU on 31 October 2019. There is much uncertainty as to the effect that this will have on the laws and regulations governing all areas of commercial activity, including the healthcare, pharmaceutical/biotech and medical devices sectors, as it is not yet known whether:

• the Withdrawal Agreement negotiated by the former prime minister, Mrs Theresa May, and her government will be ratified by the UK Parliament as it stands;
• the current prime minister, Mr Boris Johnson, and his government will negotiate amendments to the Withdrawal Agreement or a new exit agreement with the EU;
• the UK will leave without a deal (referred to hereinafter as a “no deal Brexit”); or
• the deadline for leaving the EU, extended from 29 March to 31 October 2019, will be extended further.

The issues that the different scenarios give rise to are outside the scope of this Handbook. However, the key points are as follows:

• The European Union (Withdrawal) Act 2018 came into effect on 25 June 2018 and enables the transposition of already-existing and directly applicable EU law into UK law so that, in general terms, current EU law will be converted into and continue as UK law at the moment of exit (with changes where necessary to make sure that the rules continue to work in a UK context – for example by transferring responsibilities of the EMA in the regulation of medicines to the MHRA).
• Therefore, if a no deal Brexit occurs, then the UK’s involvement in the EU will come to an immediate end and EU laws will cease to have effect (save insofar as they have been incorporated into UK law) without a new frame- work having been put in place for a future relationship between the UK and the EU.
• If, on the other hand, there is a negotiated withdrawal in line with the Withdrawal Agreement, a transition period will be entered, which is due to end on 31 December 2020 (although it can be extended by agreement between the EU and UK). During this transition period the UK will continue to be treated as a member state of the EU (subject to all existing EU laws as well as new ones that come into being during the period) but it will not take part in any decision-making and will no longer be a part of any the EU institutions, agencies and bodies. Therefore, for example, the UK will not have any say in the grant of market authorisations for new medicines by the EMA. The intention is that, during the transition period, a new framework governing the future relationship between the UK and the EU will be negotiated and put in place.

The implications for healthcare institutions and pharma/biotech and medical devices companies are numerous, particularly on a no deal Brexit. Accordingly, the UK government has published detailed guidance to enable them to prepare for a no deal scenario. This guidance is being updated as the 31 October dead- line approaches and there will also be a public consultation during Autumn 2019. In addition, the UK Parliament has passed a series of statutory instruments under the powers given by the Withdrawal Act to retain and modify EU law and generally make provision for a no deal Brexit. Relevant statutory instruments for the life sciences field are the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019/7751 and the Medicines For Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019/774.

In summary, the Human Medicines (Amendment etc.) (EU Exit) Regulations:

• amend the HMR by revoking and restating all relevant EU law so that all law governing the regulation of medicinal products is contained in one domestic instrument;
• allow the MHRA to function as a standalone regulator for medicines taking on the roles currently conducted by the EMA (and other EU bodies);
• provide for the automatic conversion of marketing authorisations granted under the CP to a UK marketing authorisation (unless the MAH requests otherwise) and for new routes for the authorisation of medicines (the “targeted” and “accelerated” assessment routes) to replace the CP (and other EU) routes as they will cease to have effect for the UK upon exit;
• provide for a new conditional marketing authorisation scheme for medicinal products that fulfil an unmet medical need;
• maintain the ability for abridged applications for marketing authorisations, including where the reference product is approved by a converted authorisation granted under the CP or was approved under an authorisation granted under the CP before exit day but which did not convert to a UK authorisation;
• maintain the current data and marketing exclusivity periods;
• ensure that a UK-based MAH and a UK-based qualified person for pharmacovigilance are in place for all medicines with a UK marketing authorisation (and the same for holders of registrations for traditional herbal and homeopathic medicines);
• maintain the current rules on the advertising of medicines; and
• modify the MHRA’s fees.

The Medicines For Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations:

• amend the Medicines for Human Use (Clinical Trials) Regulations 2004 so that all interventional clinical trials conducted in the UK are authorised by the MHRA, have a favourable ethics opinion and are conducted in accordance with good clinical practice;
• allow the MHRA to operate as regulator outside the EU system for clinical trials and taking on the roles currently conducted by the EMA (and other EU bodies);
• maintain the ability for the sponsor or legal representative for a trial to be based in the UK or a country on an approved list (which will initially include all EEA countries); and
• with the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019, align transparency provisions with those currently operating in the EU, including the strengthened provisions that are to be introduced by Regulation (EU) No 536/2014 (if that Regulation has not come into force by exit day), and provide for a UK portal that will give UK public, patients, clinicians and researchers a single reference point for all UK clinical trials.

The MHRA has issued guidance supplementing both of the above Regulations, including specific guidance on the new assessment routes which includes a third “rolling review” route. This is aimed at reducing the attrition rate for applications by giving ongoing guidance to applicants so that they avoid regulatory pitfalls.

Similar regulations (The Medical Devices (Amendment etc.) (EU Exit) Regulations 2019/792) and MHRA guidance have been issued regarding medical devices. Essentially these Regulations amend the MDR so that it mirrors all the key elements of the EU MDR and EU IVDR and follows the same transitional timetable for the full implementation of their provisions (the timetable is discussed in the answer to Question 2 of Regulatory, Pricing and Reimbursement Overview and, regarding labelling, in the answer to Question 35 of Chapter 3). Further, the MHRA will become the standalone regulator and registration body for all medical devices in the UK and will accordingly be given a strengthened role in market surveillance and assurance. The UK, though, intends to continue to recognise CE marks for devices, and certifications by EU Notified Bodies for low risk devices, for a limited period. Certificates from UK Notified Bodies would also continue to be recognised, though they will not be able to issue certificates for new products.

Regarding intellectual property on a no deal Brexit:

• the EPO is not an EU body nor the EPC an EU instrument, therefore most aspects of patent law will be unaffected by Brexit;
• the Patents (Amendment) (EU Exit) Regulations 2019/801 will retain such EU patent law as does exist (e.g. the Biotech Directive);
• these Regulations will also modify the law relating to SPCs as necessary to reflect the effects of Brexit (for example so that an application for an SPC will need to be based on a UK marketing authorisation or an authorisation granted by the EMA that has been converted to a UK authorisation) while retaining the requirements, timescales for grant and same term of protection as at present (i.e. based on the first authorisation to place the product on the market in the UK or EEA);
• UK registered trade marks will also continue unaffected by Brexit whereas EU trade marks will cease to have effect in the UK once exit occurs – therefore, unless the owner decides to opt-out, the UK government intends to provide owners of EU trade marks with an equivalent UK right from the date of exit, which will be granted with minimal administrative burden and for no fee;
• the same will apply to international trade marks designating the EU;
• applicants for an EU trade mark that has not been registered by the time of Brexit will need to apply within 9 months of the exit date for a UK trade mark, which will have the same filing and priority dates as the original EU application;
• these measures are contained in the Trade Marks (Amendment etc.) (EU Exit) Regulations 2019/269; and
• the UKIPO has issued guidance on the effect of a no deal Brexit on patents, SPCs, trade marks and other IP rights.

As can be seen from the above, even on a no deal Brexit, the UK is likely to remain largely aligned with EU law. If an exit agreement is reached with the EU, the alignment is likely to be closer still (and EU law may continue in effect during any transitional period). However, the UK government is taking the opportunity to streamline regulation and to consider ways in which the UK healthcare and life sciences sectors can remain competitive and benefit from any commercial advantages that departure from the EU gives rise to. The new procedures for the authorisation of medicines are examples of the latter.

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

The ins and outs of patents & trademarks in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. What are the basic requirements to obtain patent and trademark protection?

(i) Patents

There are 2 types of UK patents: a national patent applied for at (and granted by) the UK Intellectual Property Office (UKIPO) and a European patent applied for at (and granted by) the European Patent Office (EPO). An application can also enter the UKIPO or EPO routes in the national/regional phase of an application filed at the World Intellectual Property Organisation (WIPO) under the international procedure (i.e. under the Patent Co-operation Treaty 1970 (PCT)).

European patents and the EPO are provided for by the Convention on the Grant of European Patents 1973 (EPC). There are 38 contracting states to the EPC, which include all EU countries plus others such as Norway, Switzerland and Turkey. There are also extension states and validation states and, in addition, a European patent designating the UK can be used as the basis for a Hong Kong patent. The EU itself is not a party to the EPC and a European patent is not an EU right.

Under the EPC system, the EPO provides a central examination procedure for a European patent application. Upon filing an application is deemed to designate all contracting states but the applicant can subsequently decide which contracting and extension states it would in fact like the European patent to be validated in upon grant. The patent then takes effect as a bundle of national patents in those countries. For example, if an applicant were to include the UK as one of the designated countries, and attend to the necessary formalities, the patent will be granted as a European patent (UK), be registered at the UKIPO and give essentially the same rights as a national UK patent.

The basic requirements for a patent application filed at either the UKIPO or the EPO are that it meets the criteria for patentability (discussed in Question 60 below), designates the inventor and comprises a specification describing the invention, claims, any drawings referred to in the specification (or claims) and an abstract. The specification must disclose the invention in a manner clear and complete enough for the invention to be performed by a person skilled in the relevant art. The claims must define the subject matter for which protection is sought, be clear and concise, be supported by the specification and relate to a single inventive concept only. The appropriate fee must also be paid.

In addition, SPCs may be obtained that extend the protection for an authorised medicine (or plant protection product) for up to 5 years beyond the 20 year life of a patent (with possible further paediatric extension of up to 6 months) . SPCs are governed by EU Regulation 469/2009/EC and are intended to compensate a patent owner for regulatory delay in obtaining authorisation for a protected product. SPCs covering the UK, i.e. based on either a UK patent or a European patent designating the UK, are applied for to (and granted by) the UKIPO. The criteria, and length of SPC are discussed in the answer to Question 3 below.

(ii) Trade Marks

There are also 2 types of UK trade marks: national marks filed and registered at the UKIPO and EU trade marks filed and registered at the European Union Intellectual Property Office (EUIPO) (formerly known as OHIM). The EUIPO and EU trade mark are established by EU legislation and so, as an EU right, the trade mark takes effect in all countries of the EU upon registration (i.e. there is no ability similar to that for European patents to select specific countries).

A UK or EU trade mark can also be obtained through the international (Madrid) system that applies to countries that have signed up to the Madrid Protocol. International applications are made to WIPO and must be based on an existing trade mark application or registration in a member country.

The basic requirements for a trade mark application at either the UKIPO or the EUIPO are that it gives the name and address of the applicant, contains a statement of the goods and services in respect of which the mark is intended to be used (following the Nice Classification) and a representation of the mark. The appropriate fee must also be paid. The Nice Classification arranges goods and services by class. Generally the more classes applied for, the higher the fee.

 

2. What agencies or bodies regulate patents and trademarks?

As said in the answer to Question 1 above, the bodies that oversee the filing, examination and grant of patents are the UKIPO, EPO and WIPO and the bodies that oversee the filing, examination and registration of trade marks are the UKIPO, EUIPO and WIPO.

As discussed further in the answer to Question 60, the UKIPO, EPO and EUIPO also have a role in post-grant/registration challenges to the validity of patents and trade marks and the UKIPO also has jurisdiction over infringement, entitlement and other disputes relating to patents and trade marks.

Decisions of the EUIPO can be appealed to the EU’s General Court with final appeal to the Court of Justice of the European Union (CJEU). Decisions of the UKIPO can be appealed to the Chancery Division of the High Court of the Royal Courts of Justice or, in the case of trade marks, to an Appointed Person (typically a senior barrister who practises in trade mark law). Proceedings concerning the validity, infringement, entitlement and other matters concerning patents and trade marks can also be brought directly in the High Court in either the Intellectual Property Enterprise Court (IPEC), for less complex disputes between SMEs, or the Patents Court or Intellectual Property List of the Chancery Division.

 

3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?

(i) Patents

The criteria for patents are that, to be patentable, the claimed invention must be new, involve an inventive step, be capable of industrial application and not consist of excluded subject matter. Excluded subject matter is given in the Patents Act 1977 as discoveries, scientific theories, mathematical methods, aesthetic creations, mental acts, methods of playing games or doing business, computer programs, the presentation of information, and methods of treatment or diagnosis (on human or animals). The invention must also not be contrary to public policy or morality. Similar exclusions apply under the EPC to patent applications filed at the EPO.

In addition, Articles 1 to 11 of European Directive 98/44/EC on the legal protection of biotechnological inventions (the “Biotech Directive”) exclude the following from being patentable inventions:

• the human body, at the various stages of formation and development and the discovery of simple elements from it, such as the sequence (or partial sequence) of a gene;
• processes for cloning human beings;
• processes for modifying the germ line genetic identity of human beings;
• uses of human embryos for industrial or commercial purposes;
• processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial benefit to man or animal (and animals resulting from such processes); and
• any variety of animal or plant (or essentially biological process for their production) not being a microbiological process or other technical process or the product of such a process.

However, the Biotech Directive also says that inventions concerning plants or animals may be patentable if their techniques are of general applicability and that elements isolated from the human body (or otherwise produced) by means of a technical process can be patented.

These provisions of the Biotech Directive have been incorporated into the UK’s Patents Act 1977 by amendment.

All of these exclusions have implications for the patents that can be obtained in the pharmaceutical and medical device industries. As regards pharmaceuticals, there is generally little difficulty over protecting new chemical entities and the EPO (and UKIPO) have employed a legal fiction to allow patents for second medical uses of known drugs (now formalised by the revised text for the EPC known as EPC 2000). Similarly, new dosage regimes are treated as novel (rather than being excluded as methods of treatment) although they tend to run into difficulty in meeting the inventive step requirement. As regards biotech, the UKIPO’s examination guidelines note that it is established practice that a natural substance isolated for the first time, and which has no previously recognised existence, is patentable and does not lack novelty. This covers, for example, claims to newly isolated DNA sequences and antibodies (though they may be subject to objections of lack of inventive step if their isolation was no more than routine laboratory practice).

The patentability of human embryos and stem cells has been a contentious area. The CJEU held in Brüstle v Greenpeace (C-34/10; 2012) that cells that are capable of commencing the process of development of a human being are included in the term “human embryo” and are therefore unpatentable. However, since then it has been held by the CJEU in International Stem Cell Corp v Comptroller General of Patents (C-364/13; 2014) that a method of producing human embryonic stem cells from parthenogenetically-activated oocytes was patentable as the oocytes were not within the definition of “human embryo” if they were inherently incapable of developing into human beings. This decision has since been followed by the EPO in allowing stem cell related patents.

Regarding the exclusions from patentability of mental acts, computer programs and the presentation of information, all of which are of particular relevance to medical devices, the exclusions only apply “as such”. That is, if an invention includes features that go beyond the excluded subject matter then that invention may be patentable (assuming it fulfils the other patentability criteria). In practical terms this means that, when examining an application, the UKIPO or EPO are looking, respectively, for a technical effect or for technical features that solve a technical problem that takes the invention outside the exclusions and so makes it patentable. Further, the exclusion of methods of treatment and diagnosis does not prevent a claim directed to a substance or device used in that method from being patentable.

The three key requirements for the grant of an SPC in the UK are that the medicinal product is covered by a basic UK patent or European patent (UK) that is in force at the time of application, that the product has a valid marketing authorisation to place the product on the market in the UK (which must be the first such authorisation) and that there is no pre-existing SPC. An SPC cannot be obtained for a medical device certified by a CE mark only. The length of the SPC is calculated as the period from the filing date of the basic patent application to the date of the first marketing authorisation for the protected product in the EU, less 5 years, and subject to a cap of 5 years.

(ii) Trade Marks

To be registerable, a trade mark must not:

• be devoid of distinctive character;
• be descriptive of the goods or services listed in its specification (i.e. it must not relate to, for example, the quality, intended purpose, geographical origin of the goods);
• be a generic term for the goods or services;
• consist of or contain a protected emblem (e.g. the Royal arms or, if misleading or grossly offensive, the national flags of the constituent parts of the UK);
• be identical or confusingly similar to a trade mark already registered in the UK (or EU for an application for an EU trade mark);
• take advantage of or be detrimental to the reputation of an earlier well- known trade mark already registered in the UK (or EU); or
• be liable to have its use prevented by virtue of earlier third party rights (such as unregistered trade marks, copyrights or design rights).

Whereas the UKIPO and EUIPO will examine a trade mark in respect of the first 4 grounds (“absolute grounds” for refusal of registration), they will leave the owners of the earlier rights to raise the others (“relative grounds”). This can be by means of an opposition, filed following publication of the application for the trade mark, or by subsequent proceedings for cancellation (i.e. revocation or invalidation). An additional absolute ground for refusal is that a mark is applied for in bad faith (e.g. because the applicant knows that the rights to or in the mark belong to another or because it has no genuine intention to use the mark at all or across the full scope of the goods and services applied for).

With respect to allowable names for a branded medicine, EU Directive 2001/83/EC requires that an invented name should not be liable to cause confusion in print, handwriting or speech with the common name for that or for any other medicine and should not be misleading with regard to the therapeutic effects, composition and/or safety of the product. The risk of confusion is assessed by reference to factors such as the product’s characteristics (e.g. indications, route of administration, strength) and the patient population. Additionally, the invented name should not be derived from the medicines International Non-proprietary Name (INN) or contain the INN stem (published by the World Health Organisation).

Medicines may also be known by their generic name. If an INN exists for the active ingredient, that should be used exactly as published. If not, then the common name in the UK (i.e. its British Approved Name published in the British Pharmacopeia) should be used.

The MHRA is responsible under delegated powers for assessing the acceptability of names for medicines in the UK, e.g. upon an application for a new marketing authorisation. Similarly the proposed name for a drug is assessed by the (Invented) Name Review Group within the EMA for applications for marketing authorisations under the CP. Both the MHRA and the EMA have issued detailed guidance on the above and other considerations in naming medicines.

There are no specific restrictions on the trade marks that can be used in respect of medical devices, though they are subject to general consumer legislation such as the requirement under the Consumer Protection from Unfair Trading Regulations (2008/1277) that they should not create confusion with products, trade marks or trade names of competitors.

 

4. How can patents and trademarks be revoked?

(i) Patents

Granted UK patents and European patents designating the UK may be revoked through proceedings brought in the UKIPO, IPEC or Patents Court at any time post-grant. In addition, European patents may be revoked centrally through opposition proceedings brought in the EPO within 9 months of grant.
The grounds for revocation set out in the Patents Act 1977 are:

• that the claimed invention in the patent consists entirely of excluded subject matter (as discussed in the answer to Question 3 above).
• non-entitlement – the patent was granted to a person not entitled to it.
• lack of novelty (or anticipation) – the claimed invention is not new. The UK and the EPO apply worldwide novelty such that any prior public disclosure (whether as a document or a prior use) anywhere in the world of the invention claimed in a patent will invalidate that patent if the disclosure is enabling (i.e. contains sufficient teaching to enable the skilled person in the relevant field to put it into practice).
• lack of inventive step – the claimed invention is obvious. A claimed invention must be inventive over the prior art when considered by the skilled person in light of the common general knowledge in the field. If not, it will be vulnerable to revocation.
• insufficiency – the patent’s specification does not disclose the invention clearly enough and completely enough for it to be performed by the person skilled in the art. This is known as “classic” insufficiency. In recent years sufficiency has been extended to include where the invention claimed in the patent is not plausible, lacks technical contribution to the art or the skilled person is not able to reproduce the invention over the whole scope of the claim (this last is known as “Biogen” insufficiency).
• added matter – the subject matter of the patent extends beyond what was clearly and unambiguously disclosed, either explicitly or implicitly, in the application for the patent as filed.
• extension of scope of protection – an amendment to the patent’s claims post-grant has had the impermissible effect of broadening them.
• double-patenting – the Comptroller of the UKIPO is required under the Patents Act 1977 to revoke a UK patent where a European patent (UK) is granted protecting the same invention, to the same applicant (or successor in title) and with the same priority date. Double-patenting may also be raised in proceedings before the court.

Similar grounds for revocation are available under the EPC save for non-entitlement and double-patenting. However, an objection of double-patenting can be considered in an EPO opposition as it is assumed that an applicant has no legitimate interest in having 2 patents for the same invention.

(ii) Trade Marks

The grounds for invalidation of a registered trade mark mirror the grounds for refusal of registration set out in the answer to Question 3 above. While anyone can apply for invalidation of a mark on absolute grounds, only the owners of the earlier rights (or other person with an interest such as a licensee) can apply under the relative grounds.

In addition to grounds for invalidation, there are the following grounds for revocation:

• there has been no genuine use of the mark for 5 years from the date of registration or for a subsequent continuous period of 5 years;
• due to the proprietor’s acts or inactivity the trade mark has become the common name in the trade for the products or services it covers (i.e. has become generic); and
• the mark is liable to mislead the public, particularly as to the nature, quality or geographical origin of the goods or services covered.

The grounds for invalidation must exist from the date of application for the mark and accordingly it leads to a mark being removed from the EU or UK trade mark register as if it had never existed. In contrast, the grounds for revocation can only arise after a mark is registered and so the revocation of a mark takes effect from the date of the application for revocation.

Invalidation and revocation of a registered trade mark can be in whole or in part (e.g. where a mark has been used for only some of the goods and/or services it covers, the mark may be partially revoked in respect of the unused goods and/or services). The proprietor of an invalidated or revoked EU trade mark may apply for the mark to be converted to a national mark in those EU countries where the grounds of objection do not apply.

Proceedings for cancellation of an EU trade mark must be brought in the EUIPO, unless they are in the form of a counterclaim to a claim for infringement, in which case they can be heard in a designated Community trade mark court (the IPEC and Chancery Division of the High Court are so designated). If proceedings for cancellation of an EU trade mark are already in being before the EUIPO, then a Community trade mark court must stay an infringement action until the cancellation proceedings are concluded. Similarly, the EUIPO should stay cancellation proceedings before it where validity is already in issue before a Community trade mark court (though it may continue the proceedings at the request of one of the parties).

Proceedings for cancellation of a UK registered trade mark can be brought in the UKIPO, IPEC or Chancery Division (Intellectual Property List).

 

5. Are foreign patents and trademarks recognized and, if so, under what circumstances?

(i) Patents

Foreign patents, including European patents that do not designate the UK, do not have any protective effect in the UK in the sense of allowing the proprietor to bring proceedings for infringement of the patent by acts carried out in the UK. However, foreign patents remain items of property that are recognised by English courts, for example in the context of entitlement disputes, and agreements concerning them are also recognised and are justiciable in the UK where jurisdiction clauses and rules allow. By way of example, in a recent case this led to the English court determining whether a licensee’s product infringed a US patent and so whether it should pay royalties.

(ii) Trade Marks

The position on foreign trade marks is similar to that for patents described above save that international marks designating the EU or UK are recognised and enforceable in the UK and that a foreign mark may acquire goodwill in the UK (e.g. through imports or internet sales). If there is sufficient goodwill, based on a genuine market for the goods in the UK, then the owner of the mark may use the tort of passing off to prevent a third party from using the mark (or a similar one) in circumstances such that consumers may be deceived into thinking that the third party’s goods are those of the trade mark owner or are endorsed by or otherwise associated with the trade mark owner.

 

6. Are there any non-patent/ trademark barriers to competition to protect medicines or devices?

Leaving commercial factors aside, and compliance with laws and regulations in areas such as product safety, the main non-IP barriers to competition relate to medicines and are the data and marketing exclusivity periods discussed in the answer to Question 6 of Regulatory, Pricing and Reimbursement Overview. As said there, these exclusivity periods protect branded medicines from generic entry for up to 11 years from the date of their approval. However, a generic company can avoid these periods by applying for a marketing authorisation based on its own clinical data (if the expense of doing this is commercially worthwhile).

 

7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?

See the answer to Question 3 above.

 

8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?

No. It makes no difference under the Patents Act 1977, the Trade Marks Act 1994 or any other legislation concerning patents and trade marks in the UK if a licensor is a foreign person or entity. Approval from appropriate bodies may be required by a licensor to enable it to conduct business in the UK and by a licensee dealing with a licensor that is subject to sanctions or is (or is owned by) a politically exposed person. However, these points are outside the scope of this Chapter.

It is, though, worth noting that a patent or trade mark licence may be registered at the UKIPO in order to protect the licensee’s interest in the event of subsequent conflicting licences being granted by the licensor. Also for patents, where the licence is exclusive and has not been registered within 6 months of being entered, the exclusive licensee will not be allowed to recover its costs of any successful infringement action from the losing party for the period prior to registration. There is a similar rule in respect of trade mark licences except that it applies to non-exclusive as well as exclusive licences. Also, a licensee (whether exclusive or non-exclusive) cannot bring proceedings for infringement of a UK trade mark in the first place until the licence has been registered at the UKIPO (though this restriction does not apply to licensees of EU trade marks).

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

An intro to the legal situation for product liability in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. What types of liability are recognized in your jurisdiction?

The majority of product liability claims for medical products in the United Kingdom are brought under the Consumer Protection Act 1987 (CPA) and / or in negligence. Claimants may also have remedies under the Sale of Goods Act 1979 or under contract.

Under the CPA there is strict liability for damage wholly or partly caused to a consumer by a defect in a product. Defect is defined as where “the safety of the product is not such as persons generally are entitled to expect.” Recent case law has focused on the meaning of “defect” under the CPA.

Claims in negligence are brought on the basis of a manufacturer or supplier owing a duty of care to a Claimant which has been breached, and which has caused harm which was foreseeable.

 

2. How do these types of liabilities apply to the manufacturers of medicines and devices?

The CPA applies to the “producer” of the product. The definition of “producer” includes the manufacturer of the product. The CPA also extends liability to anyone who puts their mark on the product or who imports it into the EU in order to supply it.

A negligence claim can be brought against the manufacturer of a product provided that they owed a duty of care to a Claimant or Claimants in respect of a product.

 

3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?

Liability under the CPA only extends to the “producer” and, in some circumstances, the “supplier” of a product. Civil liability under the CPA does not extend to corporate executives or employees. In English law, a corporate body is vicariously liable for the acts or omission of its employees provided those actions took place in the course of employment. There is no requirement to name individuals in a claim.

 

4. How can a liability claim be brought?

A claim can be brought on behalf of an individual by issuing a Claim Form at court and paying the requisite fee. Proceedings setting out the details of the allegations need to be served on a Defendant within 4 months of a Claim Form being issued at court. There is a pre-action protocol which sets out the steps that should ideally be taken before resorting to issuing a claim.

Group litigation is also possible either via the court using its case management powers to manage claims with multiple claimants or via a formal Group Litigation Order.

A claim must be brought within the limitation period which is 3 years from the date on which the cause of action accrued or (if later) the date on which the consumer first discovered or should have discovered the defect.

There are some exceptions to this but the CPA includes an absolute overriding period of 10 years in favour of the supplier after which a claim cannot be brought.

If a claim is brought in negligence there is a provision whereby the Claimant can apply to the court to exercise its discretion and disapply the 3 year limitation period. This would be decided by the court at a preliminary limitation hearing and all the circumstances of the case would be taken into account.

 

5. What defenses are available?

Under the CPA a claim will be defeated if a Claimant is unable to prove that a product is defective or that the defect caused the loss.

In addition, there are 6 other defences set out in the CPA. These are:

1. that the defect is attributable to compliance with any requirement imposed by or under any enactment or any EU obligation;
2. that the Defendant did not supply the product;
3. the person proceeded against is a non-business party;
4. that the defect did not exist in the product at the relevant time;
5. the state of technical knowledge at the relevant time was such that the producer could not have been expected to discover the defect (the “development risks” defence); and
6. in respect of suppliers of component parts, if the defect constituted a defect in the subsequent product and was wholly attributable to the design of the subsequent product or to compliance by the producer of the product in question with instructions given by the producer of the subsequent product.

In a negligence claim, a claim will be defeated if a Claimant is unable to establish that there has been a breach of a relevant duty of care owed to them or that the breach of duty caused the Claimant to suffer loss. Defences are therefore available on the basis of the facts but also on the basis of expert evidence.

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

The legal framework for traditional medicines and OTC products in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?

No specific definition of complementary and alternative medicines (CAMs) is used in the UK, though “complementary” would typically refer to a CAM when used together with conventional medicines and “alternative” when used instead of a conventional medicine. There is obviously overlap between the two categories as many CAMs can be used in both ways. CAMs also cover both products and therapeutic techniques or practices.

The main product CAMs are herbal medicines and homeopathic remedies, which have the specific regulatory regimes discussed below. A further example is the essential oils used in aromatherapy. In general essential oils will only need to be licensed if they are sold as a medicine or if medicinal claims are made regarding them on labels, promotional material or websites. In such circumstances, the same considerations apply as for herbal medicines.

Therapeutic CAMs are typically practices such as acupuncture, massage therapy, osteopathy and chiropractic. Regulation of such CAMs is through the practitioners to ensure that they are properly qualified and adhere to codes of practice. Their regulation is discussed further at the end of this answer.

(i) Herbal Medicines

The regulation of herbal medicine is governed by European Directive on Traditional Herbal Medicinal Products (2004/24/EC), which is now implemented in the UK through Part 7 of the HMR. Under the HMR a product is only treated as a herbal medicine if its active ingredients are herbal substances and/or herbal preparations. “Herbal substances” are plants or part of a plant, algae, fungi or lichen, or the exudate of a plant, and can be fresh or dried but otherwise must be unprocessed. “Herbal preparations” are obtained by subjecting herbal substances to processes such as extraction, distillation, purification, concentration and fermentation.

A herbal medicine that makes medicinal claims for its use must:

• be licensed as a conventional medicine by the obtaining of a marketing authorisation through one of the routes described in the answer to Question 3 in Regulatory, Pricing and Reimbursement Overview; or
• be registered under the Traditional Herbal Medicines Registration Scheme (THMRS), which is administered by the MHRA, typically enabling the medicine to then be sold OTC.

The key difference between these routes is that for a herbal medicine to be authorised as a conventional medicine, its quality, safety and efficacy must be demonstrated through clinical trials. In contrast, registration under the THMRS does not require any evidence of efficacy through trials. Instead, permitted indications are based on traditional use, provided that the pharmacological effects are plausible on the basis of longstanding use and experience.

The requirements for registration under the THMRS are then that:

• the medicine has a history of traditional use for a continuous period of at least 30 years, with at least 15 years of this usage being within the EU;
• the applicant can file evidence of safety from a bibliographic review of safety data together with an expert report;
• the applicant can show adherence to appropriate manufacturing standards; and
• appropriate information will be provided to users in the form of a patient information leaflet.
  In addition, a product will only be eligible for registration under the THMRS if:
• by virtue of its composition and indications, it is appropriate for use without need of a medical practitioner for diagnosis, prescription or monitoring the product’s use;
• it is for administration externally, orally or inhalation; and
• it does not contain an ingredient that is either banned in herbal medicines by Part 1 of Schedule 20 of the HMR or that cannot be used in doses exceeding those given in Part 2 of Schedule 20.

These requirements mean that herbal medicines suitable for registration under the THMRS are those for minor conditions that can be treated by self-medication (for example, colds, coughs, indigestion, headaches and sleep problems). As a result, most herbal medicines registered under the scheme will be suitable for sale OTC, though some might be restricted to pharmacy sale. Registered medicines will have a registration number that starts with the letters THR. The MHRA also recommends that manufacturers use its THR certification mark on their product labels and in their patient information leaflets, but this is not compulsory.

Indications for serious conditions, or that require injection, cannot be registered through the THMRS but must be authorised as a conventional medicine. The same applies if the applicant cannot provide the necessary evidence of safety.

In addition, the HMR allows unlicensed herbal medicines to be prepared in response to a personal request to a practitioner for that practitioner to use his/ her judgment as to the treatment required. Further requirements are that the preparation takes place at the practitioner’s premises and the medicine does not contain a banned ingredient or one at a impermissible dosage.

(ii) Homeopathic Medicines

There are 3 ways in which homeopathic products may be licensed: under a product licence of right, under the so-called simplified registration scheme or under the National Rule Scheme (NRS). Both of the latter two schemes are administered by the MHRA.

Product licences of right were issued to all medicinal products on the market at the time of implementation of the Medicines Act 1968. This was intended to be a temporary arrangement, and while it was for conventional medicines, a significant number of homeopathic medicines remain licence of right despite the MHRA encouraging manufacturers to convert to one of the two registration schemes.

The simplified scheme is governed by Part 6 of the HMR. For registration under it:

• the product must be for oral or external use only;
• no product indications are permitted and no therapeutic claims can be made; and
• data must be submitted on the product’s quality, including that it is sufficiently dilute to guarantee safety (the first dilution must be at least 1 in 10,000).

The NRS applies to any homeopathic medicine that does not satisfy the requirements of the simplified scheme. The scheme is based upon the rules for marketing authorisations for a conventional medicine except that there is no requirement for pre-clinical and clinical data. Therefore the applicant must submit a dossier demonstrating pharmaceutical quality and batch-to-batch homogeneity of its product, its safety and its efficacy. However, the NRS is limited to products that are indicated for the relief of minor symptoms and minor conditions, which the MHRA describes as “those which can ordinarily and with reasonable safety be relieved or treated without the supervision or intervention of a doctor”. The MHRA’s guidance on the NRS includes a list of indicative conditions, which are similar to those listed for traditional herbal medicines above. As a result of the documentary burden and limitation to minor indications, the NRS is little used.

(iii) Other CAMs

Osteopathy and chiropractic are regulated by statute requiring practitioners to register with the General Osteopathic Council and comply with its code of practice (the Osteopathic Practice Standards). For all other complementary/alternative therapies regulation is through voluntary associations and their codes of practice. An example is the Complementary and Natural Healthcare Council, which was set up with the support of the UK government to provide a voluntary register of practitioners and which has a Code of Conduct, Ethics and Performance that all registrants must adhere to.

 

2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?

Yes, licensed or registered CAMs can be advertised directly to the public subject to the following rules. However, the advertising of unlicensed medicines, including unlicensed CAMs, is prohibited.

(i) Herbal Medicines

If a herbal medicine is licensed through the conventional medicine route, then the same provisions apply on advertising as for conventional medicines. These are discussed in the answer to Question 17 in Marketing, Manufacturing, Packaging & Labeling, Advertising.

As with conventional medicines, advertising of traditional herbal medicines registered under the THMRS is governed by Part 14 of the HMR but with the additional requirement that the advertisement must contain the words “Traditional herbal medicinal product for use in …” followed by a statement of the registered indications and then the words “exclusively based on long standing use”.

The MHRA has also issued specific guidance on the advertising of traditional herbal medicines in Appendix 1 of the Blue Guide. This guidance stresses that the above wording required by the HMR must be followed exactly. It also advises that an advert must contain at least one indication for use of the product, which must be clear and accurate (including any wording on the severity of the indication for which the product is registered, e.g. that it is for mild colds or coughs only). The rest of the guidance is primarily concerned with the claims that can be made and is discussed in answer to Question 46 below.

(ii) Homeopathic Medicines

The advertising of homeopathic medicines registered under the simplified scheme and the NRS is also governed by Part 14 of the HMR.

For homeopathic medicines registered under the simplified scheme, additional requirements apply over and above those for conventional medicines. These are that adverts must not mention any specific therapeutic indication and must not contain any details beyond those required for the product’s label. Appendix 2 of the MHRA’s Blue Guide adds to this that no therapeutic claims may be made.

For homeopathic medicines authorised under the NRS, the Blue Guide says that advertising can include the homeopathic use for the product and can make promotional claims consistent with the authorised indication, though “it must be clearly stated that the product is a homeopathic medicinal product used within the UK homeopathic tradition for that indication”.

 

3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?

(i) Herbal Medicines

Appendix 1 of the Blue Guide states that any additional claims for a traditional herbal medicine to the main indication claim (discussed in the previous answer) must be clearly set in the context that the product indications are based exclusively on long standing use. Therefore a statement such as “traditionally used as a remedy/treatment for …” is likely to be acceptable whereas claims such as “clinically proven” or “effective for …” are unlikely to be accepted. Similarly, even if limited clinical trials have been conducted, the MHRA’s position is that reference to them risks exaggerating the product’s benefits and so misleading consumers. This is particularly so in short advertisements where there is unlikely to be sufficient space to make it clear that, notwithstanding the trials, the product was registered on the basis that there was insufficient data to demonstrate efficacy.

(ii) Homeopathic Medicines

Advertising suggesting that efficacy is based on clinical trial data is not acceptable because of the risk of exaggerating the products benefits and misleading consumers.

(iii) Rules applicable to both Registered Herbal and Homeopathic Medicines

Registered traditional herbal medicines and homeopathic medicines are subject to the general rules on misleading advertising discussed in the answer to Question 17 in Marketing, Manufacturing, Packaging & Labeling, Advertising. The Blue Guide summarises these rules by saying that advertising must not:

• give the impression that a medical consultation or surgery is unnecessary;
• suggest that the effects of taking the medicine are guaranteed, are free of side effects or better than (or equivalent to) another identifiable treatment or product;
• suggest that health could be enhanced by taking the medicine or affected by not taking it;
• refer to recommendations from e.g. a scientist or healthcare professional that could encourage the consumption of medicines;
• suggest that the medicine is a foodstuff or cosmetic (or other consumer product);
• suggest that a medicine’s safety or efficacy is due to it being natural;
• be such as to lead to erroneous self-diagnosis;
• refer to claims of recovery in improper, alarming or misleading terms or use such terms in respect of pictorial representations of changes in the body due to disease or the action of a medicine.

 

4. What are the regulatory requirements for over-the- counter (non-prescription) medications?

OTC medicines include pharmacy-only and GSL medicines and the requirements for them are discussed in Regulatory, Pricing and Reimbursement Overview. In addition, as indicated above, registered traditional herbal medicines and licensed homeopathic medicines may be sold OTC from registered pharmacies and other outlets such as health food shops and clinics. The requirements for registration or licensing of these medicines are discussed in the answer to Question 1 above. However, most homeopathic medicines are unlicensed and so can only be prepared and sold in a registered pharmacy. They are prepared in accordance with the methods and standards set out in homeopathic pharmacopoeias for supply to individual patients.

 

5. Are there any limitations on locations or channels through which OTC products may be sold?

See the answer to the previous question and the answer to Question 14 of Regulatory, Pricing and Reimbursement Overview.

 

6. What health, advertising, and marketing claims may be made for OTC products?

See the answers to Question 17 in Marketing, Manufacturing, Packaging & Labeling, Advertising and Question 2 above.

 

7. Can OTC products be marketed or advertised directly to the public?

See the answers to Question 17 in Marketing, Manufacturing, Packaging & Labeling, Advertising and Question 2 above.

 

8. What is the mechanism by which a prescription-only product can be converted to an OTC product?

A POM may be converted to an OTC product (either pharmacy-only or GSL) by applying to the MHRA for reclassification. Reclassification has been encouraged by the MHRA (and the UK government), when it is acceptably safe to allow it. This is reflected in regulation 62(5) of the HMR which allows reclassification if “the [MHRA] considers that the product can with reasonable safety be sold or supplied otherwise than by, or under the supervision of, a pharmacist”. “Reasonable safety” is defined on the MHRA’s website as “where the hazard to health, the risk of misuse, or the need to take special precautions in handling is small and where wider sale would be a convenience to the purchaser”.

An application for reclassification needs to be supported by good evidence evaluating the risks to the public and how it will be managed. Such evidence may be in the form of clinical studies, opinions from healthcare practitioners and the relevant public associations. An SmPC and patient information leaflet should also be filed with the application. In response to an application, the MHRA may take advice from its committees of external experts, consult stakeholders (e.g. health professionals and relevant patient groups) and/or run a 21 day public consultation.

The proviso to the above is that, if the application is a “me-too” (i.e. an MAH has already applied for reclassification of an analogous product), then the standard procedures for variation of a marketing authorisation can be followed. The variation application must give details of the reclassified, analogous product.

The outcome of an application may be that a POM is moved entirely to pharmacy-only or GSL status or it may be additionally classified as pharmacy-only or GSL for certain conditions and/or dosages.

 

9. What are the requirements for the importation of either traditional medicines or OTC products?

A pre-condition to the import of a traditional herbal medicine or other OTC product is that the product is authorised or licensed for marketing in the UK. Then, in overview, the importer will need to apply to the MHRA for:

• a wholesaler licence if the importation is from within the EEA for supply in the UK; or
• a manufacturer/importer licence for importation from outside the EEA for supply in the UK.

To qualify for a wholesaler or manufacturer licence requires compliance with GMP or GDP respectively.
If the importer is not the MAH or licence holder for the product then it should notify the MAH or licence holder and, if the marketing authorisation was issued by the EMA, then it must notify the EMA as well. There are also trade mark considerations where the importation is parallel importation (i.e. the medicines are branded with a registered trade mark and are being imported into the UK without the consent of the brand owner). As there is no international exhaustion in the UK (or EU), importation of a branded medicine from outside the EEA without consent will constitute trade mark infringement. If the importation is from a country within the EEA, then the trade mark owner’s rights will be exhausted so long as the label affixed by the importer does not adversely affect the guarantee of origin provided by the brand name. But if the product is repackaged or more prominently re-labelled then, to avoid trade mark infringement, the importer has to comply with the 5 conditions set out by the CJEU in Bristol-Myers Squibb v Paranova (C-427/93) (extended to re-labelling, or over-stickering, by Boehringer Ingelheim v Swingard (C-348/04)). These conditions are that:

• the repackaging or re-labelling must be necessary to market the product;
• the repackaging or re-labelling does not effect the original condition of the product;
• the new packaging or labelling clearly states who repackaged or re-labelled the product and the name of the manufacturer;
• the presentation of the product must not damage the reputation of the trade mark or its owner; and
• the importer must give advance notice to the trade mark owner of the parallel importation and, on request, provide a specimen of the proposed new packaging or re-labelled product.

Failure to meet just one of these conditions will enable the trade mark owner to lawfully oppose the importation.

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

An insight into marketing, manufacturing, packaging & labeling, advertising in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?

The authorisation process is discussed in the answer to Questions 2 and 3 in Regulatory, Pricing and Reimbursement Overview.

 

2. What is the authorization process for the marketing of generic versions of these products?

The authorisation process for generic drugs is discussed in the answer to Question 6 in Regulatory, Pricing and Reimbursement Overview.

 

3. What are the typical fees for marketing approval?

The typical fees are discussed in the answer to Question 4 in Regulatory, Pricing and Reimbursement Overview.

 

4. What is the period of authorization and the renewal process?

The authorisation periods and renewal processes are discussed in the answer to Question 5 in Regulatory, Pricing and Reimbursement Overview.

 

5. What are the requirements, if any, for post-approval pharmacovigilance?

National UK and EU legislation on pharmacovigilance was largely consolidated and implemented in Part 11 of the HMR. This included the implementation of Directive 2010/84/EU, which was intended to introduce a strengthened, clarified and more proportionate pharmacovigilance regime. In particular, since June 2016 it has been mandatory for MAHs to submit periodic safety update reports (PSURs) for both centrally and nationally authorised human medicines to a central repository run by the EMA. A PSUR should summarise all data relevant to the benefits and risks of the medicine, including all studies (including on new indications), investigations on product safety, patient sup- port programs and so on.

The MHRA is responsible for overseeing compliance by MAHs with their obligations under the regime and has produced guidance in the form of the “Good Pharmacovigilance Practice” (GPvP), which sets minimum standards for compliance and which is backed up by GPvP inspections. The GPvP is extensive but the essential obligations on MAHs include operating a pharmacovigilance system that:

• has an appropriately qualified person responsible for pharmacovigilance located within the EU;
• includes maintaining a pharmacovigilance system master file (PSMF) and making it available to the MHRA for inspection within a seven day period from the date of an inspection request; and
• includes operating, monitoring, updating and regularly auditing the system and risk management system for the medicine.

As with its enforcement powers generally (discussed in the answers to Questions 8 and 9 in Regulatory, Pricing and Reimbursement Overview), the MHRA takes a risk-based approach to the scheduling and frequency of inspections and will generally give advance notice of an inspection to the MAH. The MHRA no longer requires the filing of routine GPvP compliance reports by MAHs to assist it in deciding when to conduct inspections as it has access to all PSURs. As well as routine inspections, the MHRA will conduct “triggered” inspections where it has received information of a possible GPvP breach from, for example, a whistleblower or regulatory authority in another EU state.

The MHRA also conducts inspections as the supervisory authority for authorisations granted under the CP where the MAH has located its pharmacovigilance system master file in the UK. The EMA coordinates such inspections, which are generally on a 4-year cycle. The inspections are typically conducted by the MHRA following the same approach as for its routine national inspections.

Following an inspection, a report will be issued with any proposed corrective and preventative actions required from the MAH. In the case of serious or serious and persistent breaches of GPvP, the MHRA may issue an infringement notice.

 

6. Are foreign marketing authorizations recognized?

Marketing authorisations issued outside the EEA are not recognised by the EMA or MHRA. To market a medicine in the UK, an authorisation covering the UK must be obtained through one of the procedures described in the answer to Question 3 in Regulatory, Pricing and Reimbursement Overview.

As said in the answer to Question 6 in Regulatory, Pricing and Reimbursement Overview, only applicants that are established in the EU can obtain a marketing authorisation.

 

7. Are parallel imports of medicines or devices allowed?

(i) Medicines

The parallel importation into the UK of a medicine authorised in another EU member state is permitted provided that it has no therapeutic difference to the associated UK product, it is manufactured according to good manufacturing practice, the packaging and patient information leaflet comply with EU guidance and the importer holds a wholesaler’s licence and the correct parallel import licence. If the product requires assembling or repackaging, then a manufacturer’s licence will be required as well.

Parallel import licences are granted by the MHRA, except in the case of drugs controlled under the Misuse of Drugs Act 1971, in which case an import licence from the Home Office is required. A parallel import licence from the MHRA is granted for a period of 5 years and can be renewed. The MHRA’s fees vary from £1,792 for a simple application to £18,180 for a complex one.

The patent and trade mark implications of parallel importation are discussed in Patents & Trademarks.

(ii) Devices

A medical device that has obtained its CE marking, and is already on the market in one EU country, can technically be marketed anywhere else in the EU including the UK (provided that the product meets the requirements of the relevant EU legislation). However, if the importer rebrands the device so that it is marketed under its own name or makes any changes to the product such that it is no longer covered by the CE mark, which includes changing the manufacturer’s lot or brand number, then the device will need to be re-submitted for CE marking by the importer before it can be marketed.

Certain changes will not result in the importer becoming manufacturer of the device, and so having to resubmit it for CE marking, such as changing the language of the packaging and instructions or making other changes necessary for marketing in the UK as long as the original condition of the device is not affected.

An interim procedure applies for the parallel importation of self-test IVDs due to the requirement that they should be labelled in the language of the EU member state of the user. A person intending to import such devices should contact the MHRA.

 

8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?

The general law on gifts and incentives is set out in the Bribery Act 2010 (2010 Act). Healthcare organisations and/or individual medical practitioners may fall foul of the 2010 Act if any activity falls into one of the following categories of offences:

• the general offences of promising, offering or giving or requesting, agree- ing to receive or accepting an advantage (financial or otherwise), in circumstances involving the improper performance of a relevant function or activity (i.e. the offences of making or accepting a bribe for a function or activity that should be performed in good faith, impartially or as a result of a position of trust);
• the offence of promising, offering or giving an advantage (financial or otherwise) to a foreign public official (FPO) intending to (1) influence the FPO in his/her capacity as such; and (2) thereby obtain/retain business or a business advantage; and/or
• the strict liability offence committed by corporate entities that fail to prevent bribery by those acting on their behalf (their associated persons), where the bribery was intended to obtain or retain a business advantage for the corporate entity.

The guidance surrounding the Act is clear that the aim is not to stop corporate hospitality (such as gifts, entertainment and other incentives) per se, but to prevent bribery, including facilitation or “grease” payments, under the guise of corporate hospitality.

As regards the corporate offence, it is a defence for the corporate entity if it can demonstrate that it had adequate procedures in place designed to prevent bribery taking place. The procedures should be proportionate to the risks taking account of factors such as top-level commitment to anti-corruption, due diligence on potential risks, training in the company’s policies and procedures and periodic review.

More specifically for the pharmaceutical industry, the HMR contains provisions preventing the giving of free samples of medicines except on certain conditions (including that it is to a person qualified to prescribe, on an exceptional basis and in response to a request) and preventing the use of inducements or hospitality in the promotion of medicines except in limited circumstances. Gifts and benefits may only be given, offered or promised, if they are inexpensive and relevant to the practice of medicine or pharmacy. Hospitality can only be provided if strictly limited to the purpose of the meeting (i.e. the promotion of a medicine) and the recipient is a healthcare professional.

In addition, the ABPI has a Code of Practice for the Pharmaceutical Industry (the “ABPI Code”), which all of its members have to agree to abide by (a large number of non-members have also agreed to follow it). The current edition of the ABPI Code was issued in 2019. Although primarily aimed at the self-regulation of the promotion and advertising of medicines, the ABPI Code also includes provisions against inducements to health professionals to prescribe, recommend, supply or buy medicines unless they are, for example, inexpensive items that are part of a formal patient support programme or inexpensive notebooks, pens and pencils for use at promotional meetings and conferences. The ABPI Code also includes provisions on the disclosure of transfers of value to health professionals and healthcare organisations. Typical transfers of value include donations, grants and benefits in kind, contracts awarded, sponsorship and fees and expenses paid.

A similar code of practice is issued by the Association of British Healthcare Industries (ABHI) in respect of the medical technology industry called the “Code of Ethical Business Practice” (the “ABHI Code”). Like the ABPI Code, the ABHI Code gives a self-regulatory regime that has to be signed up to by members (and non-members can sign up as well). The ABHI Code says that members may provide inexpensive educational items and/or gifts that relate to the healthcare professional’s practice, that benefit patients or that serve a genuine educational function, and are not in the form of cash or cash equivalents. More expensive items can only be provided if, amongst other things, they are not for the healthcare professional’s personal use and are related to the therapeutic areas of the member company.

 

9. How is the manufacturing of medicines and devices regulated and by which agencies?

The regulation of medicines and medical devices, and responsible agencies, is discussed in the answers to Questions 1 and 2 in Regulatory, Pricing and Reimbursement Overview.

 

10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the US Food & Drug Administration (US FDA) and/or the European Medicines Agency (EMA)?

The Good Manufacturing Practice (GMP) requirements in the UK are similar to the current practice in the US. The UK requirements are largely derived from EU legislation, including Regulation 1252/2014 and Commission Directive 2003/94/EC applying to active substances and medicines for human use. Compatibility with the FDA’s requirements on GMP is discussed further in the answer to Question 12 below.

 

11. What is the inspection regime for manufacturing facilities?

The Inspectorate Group of the Inspection and Standards Division of the MHRA (MHRA Inspectorate) conducts inspections to ensure that medicines are of consistent high quality, are appropriate to their intended use and meet the requirements of the marketing authorisation or product specification. To that end the MHRA Inspectorate has extensive regulatory powers as discussed in the answer to Question 8 in Chapter 1. As described there, and above regarding pharmacovigilance, the MHRA takes a risk-based approach to routine inspections as well as conducting triggered inspections in response to information from whistleblowers or other regulatory authorities.

In addition, the MHRA Inspectorate conducts inspections when a manufacturer applies to it for a national marketing authorisation. Where the manufacturing facilities are in the UK, such product related inspections can also be requested by the EMA in respect of marketing authorisations under the CP or using the MRP or DCP.

Before an inspection is made, unless a trigger inspection at short notice, the manufacturer has to submit a compliance report to the MHRA. During the inspection the MHRA may ask for additional documentation and may take samples. At the end the inspector will discuss deficiencies with the manufacturer and a timetable for corrective action (which will be confirmed by follow-up letter).

If the inspection reveals a critical deficiency (i.e. one that has produced or risks producing a product that is harmful to humans or one that results in a significant risk to patients) or that there are unresolved deficiencies from a previous inspection, then the manufacturer can be refused a marketing authorisation or have its existing authorisation suspended or face increased inspections.

Both the EMA and MHRA have published guidance on GMP and inspections.

As regards medical devices, manufacturing is assessed as part of the CE certification process (by reference to the standards in the Medical Devices Directives as well as international standards such as ISO 13485:2016 (on quality management systems for medical devices) and ISO 9001:2015 (on quality management systems). Further, in addition to routine surveillance and audits on recertification, following European Commission Recommendation 2013/473/EU and now formalised in the EU MDR, notified bodies are required to conduct unannounced audit visits at least once every 3 years to all holders of CE marks for devices that required a conformity assessment by a notified body to obtain certification. Unlike routine surveillance, which is focused on quality systems, unannounced audits are focused on day-to-day compliance in the manufacture of a specific product (or products) covering matters such as conformity with technical documents and legal requirements, traceability of components, assembly, packaging and quality control and can also include testing of samples.

The manufacturer will receive an audit report setting out any non-compliance found and have 60 days to respond, explaining the cause of the non-compliance and planned corrective actions. An audit could result in suspension of certification. The costs of the audit are borne by the manufacturer.

 

12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?

The FDA can carry out inspections in the EU (and vice versa). However, the EMA and FDA have cooperated in various initiatives on GMP inspections since 1998 aimed at reducing duplication and allowing better use of resources by focusing on inspections of facilities that present potentially greater risks. Thus, in June 2017, the European Commission confirmed that the FDA is competent in carrying out GMP inspections at an equivalent level to the EU. Further, in November 2017, a Mutual Recognition Agreement (MRA) on GMP inspections between the EU and FDA came into effect, with a transitional phase until July 2019 during which the FDA has been conducting capability assessments of the national regulatory authorities in each EU member state on a rolling basis. Most national authorities are now recognised as competent by the FDA (confirmation of the UK’s compatibility was given in November 2017).

The MRA is supported by confidentiality agreements allowing for the exchange of inspections reports and other information (e.g. on post-authorisation surveillance).

At present the scope of the MRA is limited to medicinal products for human use, though it will be extended to include veterinary medicines, vaccines and plasma-derived medicinal products as well.

The EU has also entered MRAs on GMP with Australia, Canada, Israel, Japan, New Zealand and Switzerland though generally they only cover exchange of GMP certificates and 2-way alert systems.

 

13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?

The European Commission has published guidance on Good Distribution Practice (GDP) for medicinal products for human use (Commission Guidelines 2013/C 343/01) and on principles of GDP for active substances for medicinal products for human use (Guidelines 2015/C 95/01). Essentially the guidance is to ensure that:

• medicines in the supply chain are properly authorised;
• medicines are stored in appropriate conditions during warehousing and transport;
• contamination by or of other products is avoided;
• there is adequate turnover of stored medicines; and
• products reach the right addressee within an appropriate timeframe. Specific requirements include, for example, that:
• medicinal products should be stored separately from other products likely to alter them and should be protected from the harmful effects of light, temperature, moisture and other external factors;
• warehouse storage facilities should have appropriate security;
• stock should be rotated according to the “first expiry, first out“ principle and medicinal products nearing their expiry date should be withdrawn immediately from saleable stock;
• inventories should be performed regularly and any irregularities investigated and documented; and
• measures should be in place to prevent spillage, breakage, contamination and mix-up during handling.

While MAHs do not require separate authorisations to distribute their products, wholesalers must be licensed by the MHRA, which requires showing compliance with EU GDP (by following the above guidelines). Similarly, manufacturers, importers and distributors of active substances for use in the manufacture of human medicines that are based in the UK must be registered with the MHRA and must comply with GMP and/or GDP.

Packaging and labelling requirements are described in the answer to the next Question.

 

14. What information must be included in medicine and device labeling?

(i) Medicines

The source legislation regarding labelling is Title V of Council Directive 2001/83/EC (as amended), and Part 13 and Schedule 24 of the HMR. The MHRA oversees compliance with labelling requirements of all medicines sold in the UK and has issued best practice guidance, based upon its move towards increased self-regulation by the pharmaceutical industry.

A first point is that, with limited exceptions, all information necessary to meet the requirements of the HMR must be in English.

Part 1 Schedule 24 sets out the key requirements for the outer and immediate packaging for medicines (POMs and OTC), though under Article 54 of Directive 2001/83/EC certain information is deemed critical: the name of the medicine (which must also be in Braille); the expression of its strength; the route of administration; its posology (a legal requirement for OTC medicines); and, any warnings required by the terms of the medicine’s marketing authorisation. This information should be placed together on the package, within the same field of view, and more prominently than other information. In addition, the full name of the medicine should appear on at least 3 non-opposing faces of the package (with the names of the active ingredient(s) immediately following).

Further key requirements are that: those excipients known to have a pharmacological effect in their own right have to be identified; and, the registered indications of OTC medicines (pharmacy-only and GSL) must be given as part of the critical information. And, under Commission Delegated Regulation (EU) 2016/161, all medicines must have a unique identifier (as well as tamper evident features).

Other non-critical information that should be given covers matters such as: whether the product is for babies, children or adults; for injectable, topical and eye products, all excipients; the MAH and authorisation number; the batch number; expiry date; and, any special storage requirements. Space should also be left on the packaging of prescription medicines for a dispensing label to be applied by the pharmacist. Particular requirements also apply to blister packs including that the name and strength of the product should, where practicable, be printed over each blister pocket or be orientated centrally across the pack. Controlled drugs should be identified by the letters “CD” in an inverted triangle.
If the label does not contain all the necessary information, then the packaging for a medicine must contain a patient information leaflet.

(ii) Medical Devices

Regulations around medical device labelling have not traditionally been as comprehensive as medicines. However, the definition of “label“ alone has expanded over the years to include a multi-lingual booklet and Instructions For Use (IFUs).

The current information requirements are set out in the UK MDR by reference to the Annexes of the Medical Devices Directives discussed in the answer to Question 2 in Regulatory, Pricing and Reimbursement Overview. As with medicines, for devices sold in the UK, the label information has to be in English. The required information is then:

• the CE mark in visible, legible and indelible form and the notified body or conformity assessment body identification number;
• name and address of the manufacturer (if imported then the EU representative);
• details to identify the device and the contents of the packaging;
• batch code/serial number;
• where appropriate:

• the word “sterile”;
• the use-by date (as year and month);
• that the device is for single use;
• that the device is “custom made”;
• that the device is exclusively for clinical investigations; o the method of sterilization;

• any special storage and/or handling conditions and/or operating instructions;
• warnings/precautions;
• intended purpose (if not obvious to the end-user); and
• if no use-by date, the year of manufacture (which can be part of the batch or serial number).

The IFU must also contain the above items (except for batch number and use-by date) and further information such as: any undesirable side-effects; information on installation (including calibration) and connections with other devices; risks; sterilisation methods; and, contraindications and precautions. IFUs for implantable devices must have additional information for both the doctor and the patient regarding implantation, connections, interference risks, battery life, use and date of issue. Similarly IFUs for IVDs should contain details such as reagents used, storage conditions for the device once opened and reagents, the type of specimen to be used, the measurement procedure and mathematical approach for calculating the analytical result, and instructions on re-use and for self-testing.

However, while maintaining many of the above information requirements, the incoming EU MDR and EU IVDR will add certain significant aspects to them, requiring advance preparations by medical device manufacturers to avoid the risk that their products cease to be marketable in the EU. The key additional label requirements include:

• inclusion of a standardised symbol to indicate that the package contains a medical device;
• use of a Unique Device Identification (UDI) (as part of the global UDI initiative);
• inclusion of the symbol, name and address of any EU representative for a device; and
• more detailed information on warnings/precautions (information which under current rules can be in the IFU will have to be included in the label, though the EU MDR says it can be kept to a minimum).

It should also be mentioned that the use of symbols to communicate information, such as where a device is re-usable and any use-by date, is increasing and is covered by ISO 15223-1:2012.

 

15. What additional information may be included in labeling and packaging?

See the answer to Question 14 above. In addition, for medicines, non-statutory information useful for the patient can be included in the label and patient information leaflet but it should be compatible with the SmPC and not be promotional. It could, for example, be additional information about the way in which the medicine works and the disease it is intended to treat, which is of benefit to patients on long-term medication. QR codes (i.e. barcodes) can also be on packaging provided they are subordinate in prominence and placement to the statutory information.

Further, a member state may require that certain additional information on price, reimbursement conditions, legal supply and authenticity and identification should be included on the package. Due to the principle of free movement of goods, this information should be contained in a so-called “blue box” in the official language of the member state concerned so that it is distinct from the other information on the packaging. The blue box should be located in the same position for the particular medicine’s packaging in all member states. The only information that the UK requires to go in the blue box is the legal status of the medicine, i.e. “POM” or “P” (for pharmacy medicines).

 

16. What items may not be included in labeling and packaging?

The legislation discussed in the answer to Question 14 is drafted in terms of what should (or can) be included in labelling or on packaging, rather than what should not be. However, the MHRA’s guidance on labelling of medicines identifies the following as statements or wording that should not be used:

• promotional information;
• negative statements – only positive statements should be used to avoid ambiguity, for example if a product is for intravenous use only, it should say so whereas other products should not say “Not for intravenous use”;
• medical terminology (unless there is evidence from user testing that it is understood); and
• abbreviations of the medicine’s name as registered in the SmPC.

The guidance also advises on the use of statements about conditions, indications, speed of action, formulation and population groups for OTC medicines aimed at avoiding them being misleading and being compatible with any SmPC. For example, a product that relieves symptoms should not be said to cure the underlying condition. Nor should a statement such as “suitable for people with diabetes” be used if, although a product is sucrose free, it contains other sugars.

Medical devices are subject to similar general rules against misleading medical claims and also a disclaimer such as “this is not a medical device” should not be applied to a device if medical claims are made or implied elsewhere in its labelling, packaging or IFU etc.

 

17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?

(i) Medicines

The advertising of medicines in the UK is regulated by a combination of legislation and industry codes of practice. The relevant legislation is Titles VIII and VIIIa of Directive 2001/83/EC implemented by Part 14 of the HMR. Guidance on the HMR is provided by the MHRA’s “Blue Guide”, which construes advertising broadly as any thing or activity, using any form of media, intended to encourage the prescribing or use of medicines, though it does not include e.g. factual statements, price lists, reference materials or the packaging and patient information leaflet.

The codes of practice, aimed at self-regulation by the industry, are:

• the ABPI Code – as mentioned in the answer to Question 8 above, all member companies of the ABPI are obliged to abide by the ABPI Code, and non-member companies have also agreed to comply with it. The ABPI Code reflects, and in some respects goes beyond the requirements of, the relevant law on the promotion of POMs to healthcare professionals and certain administrative staff. It also covers information made available to the public about POMs. The ABPI Code is administered by the Prescription Medicines Code of Practice Authority (PMCPA).
  • the advertising codes issued by the Proprietary Association of Great Britain (PAGB), which represents manufacturers of branded OTC medicines and self-care medical devices. PAGB publishes 2 advertising codes – one on advertising of OTC medicines (and registered traditional herbal medicines) to consumers and the other on advertising to prescribers.

More generally, the promotion of medicines also has to comply with the standards set for all advertising in the UK, for which the Advertising Standards Authority (ASA) is the UK’s independent regulator and issues codes of practice (for broadcast and non-broadcast adverts) (the “ASA Codes”). The MHRA works with the ASA, and its committee that drafts the codes. Further, there is legislation concerning broadcast advertising as well as provisions governing advertising generally in consumer legislation such as the Business Protection from Misleading Marketing Regulations 2008/1276 and Consumer Protection from Unfair Trading Regulations 2008/1276. As their names imply, these Regulations prohibit misleading advertising, including misleading comparative advertising.

Given these numerous sources, only the general rules identified in the Blue Guide and the key provisions regarding the promotion of medicines to healthcare professionals will be discussed further. The key provisions concerning the general public are discussed in the answer to Question 20 below.

The Blue Guide’s general rules are that:

• it is not permitted to advertise medicines that are not licensed, save in limited circumstances such as providing factual information regarding new treatments expected to give rise to significant costs advantages over standard treatments.
• additional restrictions apply to the advertising of traditional herbal or homeopathic registration (discussed in the answer to Question 2 of Traditional Medicines and OTC Products).
• all advertisements must:

• comply with the particulars listed in the SmPC (the advert can contain additional evidence if that evidence can be substantiated and is not inconsistent with the SmPC);
• encourage the rational use of medicines, in particular by not exaggerating the properties of a product; and
• not be misleading, particularly as to the potential benefits or risks of a medicine.

Advertisements to healthcare professionals must then include the following information:

• the authorisation or registration number and holder;
• the legal classification of the product as a POM, pharmacy medicine or GSL;
• the name of the product;
• a list of the active ingredients(s), using their common names and placed next to the most prominent display of the product name;
• the medicine’s indication(s) consistent with its marketing authorisation or registration details;
• a summary of the information in the SmPC on adverse reactions, contraindications, dosage and method of administration (where not obvious), which must be printed clearly and legibly and in such position that their relationship to the claims and indications for the product can be readily appreciated; and
• the cost.

These requirements are modified for short-form advertisements (which must be no larger than 420 square centimetres in size).

In any form of advertisement, it is not acceptable to state or imply that a medicine is safe, though it can be said that it is safer than an alternative or well tolerated, in both cases if supported by evidence.

(ii) Medical Devices

There is a general assumption that there is a lower risk of misuse with medical devices compared to medicines. As a result, the legislative control on advertising of medical device is not as comprehensive as that for medicines. Nor do the industry codes or the Blue Guide discussed above apply. Therefore, advertising of medical devices is primarily governed by the general consumer legislation mentioned above and the ABHI and ASA Codes.

The ABHI Code only applies to advertisements directed at healthcare professionals. Essentially the ABHI Code requires that:

• advertisements must be accurate, balanced, fair, objective, unambiguous and supported by up to date substantiation for all information, claims and comparisons;
• claims and comparisons must accurately balance all relevant evidence, which should be scientifically robust;
• advertisements should encourage the appropriate use of a device; and
• comparisons with other medical devices should not be misleading, should be supported by clear evidence, should compare devices for the same intended purposes and should not create confusion with the competitor’s device or trade marks or otherwise take advantage of or denigrate the competitor’s mark, product or services;
• advertisements should not promote off-label use.

The ASA’s non-broadcasting code includes similar provisions on the need for robust evidence to support efficacy claims and advises that advertisements should not state or imply that a medical device can be used to diagnose or treat medical conditions unless under the supervision of a suitably qualified health professional. The ASA’s broadcasting code allows testimonials and endorsements of devices by suitably qualified healthcare professionals if genuine, supported by documentary evidence and any direct financial interest is made clear.

The packaging and labelling requirements discussed in the answers to Questions 13 to 16 above, should also be borne in mind.

 

18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?

As regards places from which medicines can be sold, see the answer to Question 14 of Regulatory, Pricing and Reimbursement Overview. However, medicines can also be sold at a distance or over the Internet, and delivered to the patient by post, subject to the National Health Service (Pharmaceutical and Local Pharmaceutical Services) Regulations 2013. Guidance for such pharmacies is provided by the General Pharmaceutical Council (GPhC). In essence, the same requirement that POMs and pharmacy medicines can only be sold or supplied from a registered pharmacy under the supervision of a pharmacist still applies to pharmacies operating at a distance (e.g. by post) or over the Internet. The 2013 Regulations also provide that none of the essential services of a pharmacy should be provided face-to-face to a patient from a distance-selling pharmacy, that it must be capable of providing those essential services during all of its core opening hours and that it cannot restrict those services to particular locations in England or particular categories of patients. Nor can the pharmacy be in the same building as a doctor’s practice.

The Guidance further advises that the premises used must meet the standards for a registered pharmacy, patients should consent to the form of service being provided and it must not restrict the patent’s choice of pharmacy or unduly influence or mislead patients (e.g. about the identity and location of the pharmacy).

As regards web-based pharmacies, they must be registered with the MHRA, must display the “distance selling” logo on each webpage offering medicines and must provide MHRA contact details and link to its website. Further, the GPhC’s guidance advises that the website should display certain other information prominently such as its GPhC registration number, the name of the superintendent pharmacist, details of the registered pharmacy and says that the website may also display the voluntary GPhC logo. General legislation applicable to e-commerce will also need to be complied with.

Medical devices (that are correctly CE marked and have details of the appropriate notified body number) can either be supplied to patients on prescription or OTC. Where on prescription the above requirements apply to distance-selling. Otherwise general e-commerce legislation applies, though the EU MDR and EU IVDR cover distance-selling over the internet saying that their provisions generally have to be complied with and that the person or entity running the website has to make the EU declaration(s) of conformity for the device(s) being sold available upon request.

 

19. What are the restrictions and requirements for electronic marketing and advertising via email, by internet, social media, and other channels?

The same restrictions and requirements apply as are discussed in the answers to the above Questions.

The Blue Guide gives the MHRA’s opinion that Internet advertising for POMs is only acceptable on websites directed at healthcare professionals. Such websites (or the relevant sections of them) should ideally be access restricted. If no restriction is applied, and the website includes information and advertising aimed at both healthcare professionals and the general public, then these aspects should be clearly separated and clearly marked for the relevant target audience. To show that material on an open access website is “wholly or mainly directed” at healthcare professionals, the public areas should give adequate non-promotional information such that the public do not need to go to the sections for healthcare professionals (unless they choose to seek further detailed information, which should not be encouraged).

 

20. May medicines and devices be advertised or sold directly to consumers?

(i) Medicines

The background to and general rules on the advertising of medicines are discussed in the answer to Question 17. Specific rules concerning advertising aimed at the general public in the HMR are that:

• medicines cannot be sold or supplied for promotional purposes to a person who is not qualified to prescribe medicines.
• advertisements cannot be directed to the public that:

• are likely to lead to the use of a medicine to induce an abortion;
• are likely to lead to the use of a POM (i.e. advertising to the public should relate to OTC medicines only);
• relate to a medicine containing a narcotic or psychotropic substance; o state or imply that a consultation or operation is unnecessary, offer diagnoses or treatment by post or electronic communication or that may lead to an erroneous self-diagnosis;
• suggest that the effects of taking a medicine are guaranteed, better than another medicine or free of adverse reactions;
• are misleading or likely to cause alarm as to the effects of a disease or of a medicine;
• suggest it is not a medicinal product or is safe or efficacious due to the fact that it is natural;
• refer to a recommendation by a scientist, healthcare professional or celebrity; or
• contain materials primarily directed to children.

• it must be clear that it is an advertisement and the product a medicine and the advertisement must include the product name, the common name of the active ingredient (if there is only one), information on correct use and a clear invitation to read the instructions on the package or in the patient information leaflet.

The Blue Guide expands on the above requirements, for example stating that comparative claims for one medicine against another are prohibited (though comparisons to e.g. “standard tablets” are permissible). Claims that a product is e.g. “fast acting” or “provides 24 hour relief ” must be substantiated with clinical data (and brought to the target audience’s attention). Also, advertisements should not state that a product has MHRA or DHSC approval, or suggest that it is special or better than other medicines because it has approval.

In addition, the Cancer Act 1939 prohibits advertisements to the public that offer to treat cancer or prescribe a remedy for its treatment.

(ii) Devices

Devices can be sold directly to consumers but the device must be CE marked and can only be promoted for its intended use as set out in its labelling, instruction for use and technical file. Advertising to consumers is subject to the ASA Codes and the general consumer legislation discussed in the answer to Question 17.

 

21. How is compliance monitored?

Advertising compliance is monitored via the MHRA and industry self-regulation as discussed above in the answers to Questions 17 and 19.

The MHRA has the following powers enabling it to monitor and control advertising:

• checking advertising for compliance with the law prior to publication (vetting);
• monitoring of published advertising material for medicines;
• complaints handling about advertising; and
• enforcement including through criminal or civil proceedings (most breaches of the HMR’s provisions on advertising constitute a criminal offence).

The ABPI Code, and the complaints procedures under it, is administered by the PMCPA. While the PMCPA cannot approve advertising, it can offer guidance and training on what is acceptable. The ABHI Code complaints procedure is administered by the ABHI’s secretariat.

The ASA Codes are written by the Committees of Advertising Practice (CAP) and ASA and CAP together give training and guidance to industry. They also monitor advertisements and ASA runs a complaints procedure.

 

22. What are the potential penalties for noncompliance?

The HMR enables the MHRA to enforce penalties for non-compliance for various offences such as misleading advertising or failing to display the EU distance selling logo on websites selling medicines online. These powers, the MHRA’s approach to enforcement and the potential penalties are discussed in the answer to Question 9 in Regulatory, Pricing and Reimbursement Overview. The civil sanctions include the ability to require pre-vetting of advertisements and to require publication of a corrective statement targeted to the audience that saw the original advertisement and clearly stating that it is issued at the request of the MHRA.

Where a company is found by the PMCPA to be in breach of the ABPI Code, it must undertake to cease the practice complained of and give details of the action being taken to implement the ruling and to avoid such breaches in the future. Sanctions for more serious breaches include the issue of corrective statements, public reprimands and suspension or expulsion from the ABPI. A similar set of sanctions applies for breach of the ABHI Code.

The approach of the ASA to breach of its codes is to work with the defaulting companies to help them comply in the future. For persistent offenders, it can require the amendment or withdrawal of an advertisement (including online ones), issue alerts to members (including the media) advising them to withhold advertising space, require pre-vetting or refer the offender to bodies such as Trading Standards (which enforces consumer protection legislation) or Ofcom (the UK body which regulates broadcasting).

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

A brief overview of the situation regarding preclinical and clinical trial requirements in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?

There is no requirement to conduct clinical trials locally to receive marketing approval. The steps that have to be complied with in order to obtain authorisation to develop, test and market a product are dealt with in the answer to Regulatory, Pricing and Reimbursement Overview, Question 3.

 

2. How are clinical trials funded?

Clinical trials in the UK are funded by a variety of different public and private organisations:

• charities (normally focused on a particular disease);
• UK government through organisations such as the National Institute for Health Research (NIHR) or the Medical Research Council (MRC);
• pharmaceutical companies; and
• international organisations.

 

3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?

As a first step, preclinical studies are carried out to evaluate the safety of a drug and its potential applications. These studies provide important information, including about the toxicity of a drug. If the studies are promising, then the next step is to prepare a clinical trial protocol which is required to obtain the necessary authorisation to carry out a clinical trial in humans.

A clinical trial protocol should set out how the trial will run and needs to be approved by various groups of people before a clinical trial can commence. This includes:

• peer review; and
• ethical approval by a Research Ethics Committee or REC.

In addition, all clinical trials need to be authorised by the MHRA.

If a trial is taking part in an NHS hospital, each hospital will need to get approval from their NHS Research and Development department.

 

4. What are the requirements for consent by participants in clinical trials?

Participants must give their informed consent in writing before being entered into a clinical trial.

For each trial, specific consent documentation must be developed and approved by the ethics committee. This should consist of a participant information sheet and consent form so that a participant is clear about the objectives, nature and risks of the trial.

Participants in clinical trials are encouraged to ask questions before providing their consent to participate. As a result of case law, informed consent must be focused on the individual participant and based on a genuine two-way dialogue.

Throughout the trial, the subject’s willingness to continue participating in a trial should be checked and reaffirmed periodically.

If new developments come to light during the trial, which could affect consent, these must be brought to the attention of participants.

 

5. May participants in clinical trials be compensated?

Yes, participants can receive a fee for participation in a trial in addition to expenses. Fees vary depending on the type and extent of the trial.

 

6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?

All clinical trials must be conducted in accordance with the principles of good clinical practice to protect the safety of the clinical trial participants.

Participants in clinical trials in the UK are protected because of substantial regulation imposed and enforced by the MHRA. Companies engaging in clinical trials are legally bound to comply with legislation in order to protect patient safety and government bodies, such as the MHRA, carry out regular inspections to ensure compliance.

In addition, before patients can be enrolled on a trial, a medical ethics committee must approve the ethicality of a trial.

The sponsor of the clinical trial is required to maintain indemnity insurance to protect against the risk of harm to clinical trials participants.

Where a contract research organisation (CRO) is involved, it is typical that a clinical trial agreement is put in place which sets out the rights and responsibilities of the CRO and also ensures that the sponsor fulfils their legal obligations.

The clinical trial agreement sets out the indemnification procedure. This information is provided to participants. In addition individual clinicians involved in the clinical trial would be personally liable in the event of any negligence on their part, either through NHS indemnity or through a private insurance company.

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms

Also from this Legal Handbook

All about regulatory, pricing and reimbursement overview in United Kingdom. Prepared in association with Clyde & Co, a leading law firm in United Kingdom, this is an extract from The Pharma Legal Handbook: United Kingdom, available to purchase here for USD 99.

 

1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?

Although the United Kingdom (UK) is negotiating its withdrawal from the European Union (EU), as of now, the UK remains a member of the EU and so subject to all EU legislation, including that on medicines and medical devices. Running in parallel to, and closely aligned with the EU legislation and bodies, are the UK’s national legislation and bodies. Both systems are described below. As the regulation of veterinary medicines is similar to that for human medicines, this Handbook will focus on human medicines only.

The EU legal framework is based on Regulation (EC) No. 726/2004 (as amended), which established the European Medicines Agency (EMA). The EMA has been operating for over 24 years and acts as the European regulatory authority with jurisdiction over drugs (human and veterinary), biologicals and medical devices across the EU. However, EU-wide marketing authorisations for medicines are actually granted by the European Commission, on the EMA’s advice, rather than by the EMA itself. Within the EMA, the Committee for Medicinal Products for Human Use (CHMP) is responsible for the evaluation of medicines for human use under the centralised procedure (discussed in the answer to Question 3) as well as providing advice to companies developing new medicines and preparing scientific guidelines and regulatory guidance for applicants for marketing authorisations.

The UK’s domestic regulatory authority is the Medicines and Healthcare Products Regulatory Agency (MHRA), which was established in 2003. It is a government agency and is responsible for regulating medicinal products (for human and veterinary use) and medical devices in the UK as well as blood and blood products and generally regulating the pharmaceutical market in the UK (e.g. through manufacturers and wholesalers licences, the regulation of clinical trials conducted in the UK and the investigation of breaches of licences and of harmful incidents with associated enforcement powers). There are two independent bodies of experts that advise the MHRA, the Commission on Human Medicines and the Committee on the Safety of Devices.

If and when the UK leaves the EU, the MHRA will become the sole authority for the UK.

 

2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?

Under the EU legal framework, healthcare can be split into two major groups: (i) pharmaceuticals (including drugs and biologicals); and (ii) medical devices. The legal requirements for the authorisation of pharmaceuticals and medical devices are very different, even though the overall aim of the regulatory regimes for both categories is to ensure that products are safe and effective for patient consumption or use.

(a) Authorisation

(i) Medicines

As said above, the main EU legislation that governs the licensing (and monitoring) of medicines is Regulation (EC) No. 726/2004 (as amended) and Directive 2001/83/EC. The latter is implemented in the UK through the Human Medicines Regulations 2012 (SI 2012/1916) (as amended) (HMR), which also consolidates much of the prior legislation relating to medicines including relevant parts of the Medicines Act 1968. The HMR therefore governs matters such as the authorisation, manufacturing, importation, distribution, supply and advertising of medicines as well as pharmacovigilance.

(ii) Medical Devices

Generally medical devices cannot be marketed in the UK (or in the EU) without a CE mark. However, the EU legislative framework for medical devices has recently been revamped through Regulation (EU) 2017/745 on Medical Devices (EU MDR) and Regulation 2017/746 on In Vitro Diagnostic Medical Devices (EU IVDR), both of which came into force on 25 May 2017. They are subject to 3- and 5-year transitional periods respectively, during which time devices can be placed on the market either under the existing legislation or under the Regulations. The existing legislation being replaced by these Regulations is, for medical devices, Council Directives 93/42/EEC (medical devices) and 90/385/EEC (active implant- able medical devices), and, for in vitro devices, Directive 98/79/EC and Commission Decision 2010/227/EU (collectively the “Medical Devices Directives”). The Medical Devices Directives were mostly transposed into UK law through the Medical Devices Regulations 2002 (SI 2002/618, as amended) (UK MDR).

(b) Pricing and Reimbursement

(i) Medicines

While manufacturers can be said generally to have freedom of pricing, there are a number of tools used to ensure value for money and cost control for medicine pricing. Thus, for branded medicines supplied through the UK’s National Health System (NHS), price is regulated by either the Voluntary Scheme for Branded Medicines Pricing And Access (the “Voluntary Scheme”), which applies for 5 years from 1 January 2019 replacing the prior 5-year voluntary schemes known collectively as the Pharmaceutical Price Regulation Scheme, or by what is known as the “Statutory Scheme“, the current version of which came into effect on 1 April 2018. These pricing schemes are discussed further in the answer to Question 12 and reimbursement in the answer to Question 13.

The above schemes do not apply to medicines that are supplied on private (i.e. non-NHS) prescriptions or that are otherwise supplied outside the NHS system (described in the answer to Question 10).

The price of unbranded generic drugs is set by the Drug Tariff. This is a monthly price list produced by the NHS of the drugs and devices that have been approved for reimbursement. The prices are set by the NHS Prescription Services by a number of mechanisms, typically by reference to competing products.
The Health Service Medical Supplies (Costs) Act 2017 was introduced to give the government additional powers to control the price of drugs, particularly unbranded generic products, and so prevent manufacturers from de-branding in order to significantly increase prices.

(ii) Medical devices

A medical device manufacturer is generally free to set its own price for its product (subject to negotiation with the NHS) unless the device falls within one of the 4 categories that are covered by Part IX of the Drug Tariff. Part IX covers dressings, incontinence devices, stoma devices and chemical reagents. The “entry price” for Part IX devices will generally be set by reference to similar products, though the manufacturer can make representations as to why the price should be different and for annual price increases. The actual price paid by dispensers such as pharmacies, doctors etc. to the manufacturer (or wholesaler) can be negotiated but the Drug Tariff price, and the fact that a patient would need to pay privately for any device costing more than that, means that the Drug Tariff price will generally be followed.

 

3. What are the steps to obtaining authorization to develop, test, and market a product?

(a) Clinical Trials & Investigations

(i) Medicines

The authorisation of clinical trials for medicines is discussed in Chapter 2.

(ii) Medical devices

Medical devices are divided into Classes I, IIa, IIb and III on a risk-based system with the criteria for classification being set out in Annex IX of Council Directive 93/42/EEC. Class I are low risk, Classes IIa and IIb medium risk and Class III high risk. The higher the risk, the more rigorous the assessment required.

Thus Class I products may only require a clinical evaluation (as also set out in the Medical Devices Directives). The evaluation is aimed at demonstrating the safety and performance of the device when used as intended, without being unduly burdensome, and the results are set out in a report for use in support of the CE marking. Evaluations should, though, be repeated periodically throughout the life cycle of the device.

Other Class I devices and higher risk Classes require a clinical investigation as part of the process for obtaining a CE mark. The requirements for a clinical investigation are set out in the Medical Devices Directives and are to assess the safety and clinical performance of the device and whether it is suitable for the intended purpose and populations. A clinical investigation should be notified to the MHRA at least 60 days before it is due to start. The MHRA will assess the safety and performance of the device and the design of the proposed clinical investigation and at the end of its 60-day assessment period will notify the applicant whether the investigation can proceed or not.

The European Commission issues guidance on the conduct of clinical evaluations and investigations.

(b) Authorisation

(i) Medicines

There are four principle routes by which a marketing authorisation for a medicine can be obtained, these are:

The centralised procedure (CP) – applications are made to the EMA and result in a single marketing authorisation that is valid in all EU countries as well as Iceland, Liechtenstein and Norway (i.e. in the European Economic Area (EEA)). Certain medicinal products can only be licensed through the CP such as: ‘high tech’ biotechnology treatments, medicines for HIV/AIDS, cancer, diabetes and neurodegenerative diseases and Orphan drugs. This is to ensure that important medicines are readily available in all EU member states.

The national procedure, i.e. an application in a single member state to its competent authority– in the case of the UK, the MHRA. The national procedure is not much used as applicants will usually want to market new products in more than one jurisdiction.

The mutual recognition procedure (MRP) – used when an applicant already holds a marketing authorisation in one EU member state (the “reference member state”) and wishes to obtain authorisations in one or more additional member states. The authority in the reference member state will produce an assessment report and summary of product characteristics (SmPC) for review by the authorities in the additional countries (referred to as the “concerned member states”, who will also suspend any evaluations of their own on the product). If the concerned member states approve, the existing marketing authorisation is recognised and further authorisations are granted in the additional states.

The decentralised procedure (DCP) – the DCP is similar to the MRP but used where the product is not already authorised in any member state and the applicant either does not want to use the CP, or the product is not eligible for that route. One of the proposed member states will be asked by the applicant company to act as the reference member state and produce a draft assessment report and SmPC for agreement with the others (the concerned member states). The authorities in the concerned states may raise questions or objections. Once all the issues are resolved, each member state will issue a marketing authorisation permitting the product to be marketed in its country.

(ii) Medical Devices

The procedures for obtaining CE marking for a medical device are complex and varied, depending on the nature and intended use of the device. The main steps are to:

• classify the medical device;
• conduct the appropriate conformity assessment procedure for the relevant Class of device (this is to show that the device meets the requirements of the Medical Devices Directives);
• produce the technical documentation (essentially a full description of the design, manufacture and intended operation of the device, the risk assessment and conformity documentation);
• apply for certification by a notified body (i.e. a body approved for the issue of CE marks by the MHRA); and
• sign a declaration of conformity.

Certain types of medical devices are also required by Directive 93/42/EEC to be registered with a competent authority, which for the UK is the MHRA.

 

4. What are the approximate fees for each authorization?

The MHRA sets the level of fees every year in April. For 2019/2020, the fee for the national procedure is £92,753.00 and the fee for the DCP where the UK is a concerned member state is £89,556.00. For an incoming application under the MRP, the MHRA’s fee is £62,421.00.

The EMA’s fee for an application under the CP for a single pharmaceutical form and presentation is from £291,800.00.

The fees charged by notified bodies for CE marking of devices vary from one body to another and depending on the nature of the medical device so that it is not possible to give an indication of fees. The MHRA’s section of the GOV.UK website has a list of UK-based notified bodies with contact details for enquiries (notified bodies based elsewhere in the EU may also be used). In addition, the MHRA charges £100.00 for registration, notification, update or change of registered information.

 

5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?

A UK marketing authorisation will cease to be in force if the authorised medicine is not placed on the market within 3 years of grant or if the product is not sold or supplied for 3 consecutive years.

Assuming the product is marketed within the 3 years, the marketing authorisation is valid for an initial period of 5 years from the date of grant. At least 9 months before the expiry of those 5 years, the marketing authorisation holder (MAH) can apply for renewal. This requires paying the appropriate fee and filing electronically a consolidated version of the file on the quality, safety and efficacy of the product. If there are no safety concerns upon review of the file, the authorisation can be renewed for an unlimited period whereas, if there are concerns, renewal is for a further 5 years.

Renewal applications for medicines authorised through the national procedure in the UK should be filed at the MHRA and for those authorised by the CP at the EMA. For medicines authorised by the MRP and DCP, renewal applications should be filed with the competent authorities for all relevant members at the same time. If the MAH does not wish to renew an authorisation relating to the UK, it must file a cancellation form with the MHRA and notify the Department of Health & Social Care (DHSC).

CE certifications for medical devices are generally valid for 3 years, though it may only be 1 year for some high-risk devices.

 

6. How does the authorization process differ between brand- name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?

The applications for marketing authorisations under the procedures described in the answer to Question 3 can be “full” applications or “abridged” applications. Full applications are used for new active substances and require sub- mission of a dossier of information, including pharmaceutical tests, preclinical tests and clinical trials. In contrast, abridged applications can be used for medicines containing existing active substances, such as generic products, and avoid the need for such tests and trials. Where the generic product has the same qualitative and quantitative composition and active substances, and the same pharmaceutical form, as an already authorised “reference medicinal product”, and where bioequivalence can be demonstrated, the applicant can instead rely on the results of the preclinical test and clinical trials already on file for that reference medicinal product.

However, the MAH for the reference medicinal product has the benefit of data and market exclusivity periods that limit the ability of generics to rely on its tests and trials. These are:

• an 8 year data exclusivity period in which no application can cite the clinical data;
• a further 2 year period of market exclusivity during which, though a generic applicant can rely on the clinical data to obtain grant of its own marketing authorisation, it cannot place its product on the market (thus effectively giving an originator a 10 year market exclusivity period); and
• a further additional year (giving 11 years of market exclusivity) if a new indication of significant clinical benefit is added to the reference medicinal product or there is a change of classification supported by additional and significant tests and trials conducted within the initial 8 years.

These exclusivity periods are independent of any patent and/or supplementary protection certificate (SPC) protection that may exist in respect of a reference product and prevent the marketing of a generic version.

With regards to differences between local manufacturers and foreign manufacturers – only applicants that are established in the EU can obtain a marketing authorisation. “Established” means for a company, partnership or other body that it must have a registered office in the EU (e.g. for a limited company be registered at the UK’s Companies House or its equivalent in other EU countries).

 

7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?

Although the term “combination products” is commonly used within the EU pharma sector, there is no clear definition of “combination” in the EU legislation regulating medicinal products and medical devices. However, the term “medicinal product” used in EU legislation includes combinations of substances for treating or preventing disease, for restoring, correcting or modifying physiological functions or for making a medical diagnosis. Therefore combinations of drugs and drugs + biologics will be authorised through the procedures set out in the answer to Question 3, using the CP where biologics (and biosimilars) are involved. Similarly, if the principle intended action of a medical device + drug combination is achieved by the drug, then the entire product is regulated as a medicinal product.

For medical device/drug combinations in which the drug is integral (e.g. a pre-filled syringe or a patch for transdermal drug delivery) then, if the device is CE marked, the application for a marketing authorisation should include either the CE certificate or a declaration of conformity. If the device is not CE marked, but would need to be if marketed separately from the drug, then the application for marketing authorisation must include an opinion of conformity from a notified body.

If the medical device and drug are simply co-packaged (e.g. a reusable pen for insulin cartridges), then the legislation on CE marking for devices applies to it. The same applies to medical devices that contain a medicinal substance that is ancillary to the proper functioning of the device (though if the ancillary substance is derived from human blood or plasma, or is within the scope of the CP, the notified body must obtain a scientific opinion from the EMA on the quality and safety of the substance before it can issue a CE mark).

 

8. How is compliance with regulations monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?

The MHRA is responsible for monitoring compliance with medicines and medical device legislation in the UK, including the provisions on licensing, as well as monitoring of the safety and quality of medicines and devices. In addition, the MHRA carries out a sampling scheme for potentially counterfeit products. In these roles the MHRA has extensive powers derived from the HMR (for medicines), the UK MDR and consumer legislation (for medical devices) and the Police & Criminal Evidence Act 1984. Its powers include:

• taking samples of medicines/substances;
• entering and inspecting premises (both routine and unannounced inspections);
• requesting/seizing and/or retaining information/documents;
• seizing/retaining substances/articles; and
• bringing criminal prosecutions.

The MHRA takes a risk-based approach to its compliance monitoring and so, in respect of medicines, factors such as past findings and changes in the organisation of a licence-holder will be used to determine the frequency of routine inspections (the date for which is typically agreed in advance). The MHRA conducts around 1,000 inspections of manufacturers and wholesalers per year.

The MHRA also uses other schemes, such as its Yellow Card Scheme for the reporting of adverse drug reactions, to monitor and improve drug safety. Adverse reactions can be reported by anyone under the Scheme but is usually by healthcare professionals.

The MHRA cooperates closely with other UK bodies such as the police, customs and Trading Standards (which enforces consumer protection legislation) as well as the EMA (for example, notifying it of the withdrawal or suspension of a national marketing authorisation) and bodies outside the EU such as the FDA and Drug Enforcement Administration in the US.

The EMA and European Commission can take enforcement action under Regulation (EC) No. 658/2007 (as amended) in respect of marketing authorisations approved through the CP where an MAH is in breach (infringement) of obligations to which its authorisation is subject. The infringement must have significant public health implications within the EU, have effects in more than one member state or involve the EU’s interests before the action will be taken. The investigation phase is conducted by the EMA, at its own initiative or on the request of the European Commission or a member state. The EMA must issue a final report to the Commission within 18 months, which can request financial penalties. The Commission has a further 18 months to issue its statement to the MAH and may request further information from the MAH, the EMA or others before publishing its decision. If it decides that there is an infringement it can order the MAH to cease the infringement and impose financial penalties. This enforcement system works in parallel with national enforcement systems (and so aims to avoid the imposition of double penalties).

 

9. What is the potential range of penalties for noncompliance?

The MHRA will in the first instance use advice and guidance to achieve compliance, escalating through warning letters and formal cautions, then, in respect of medicines, varying, suspending or revoking authorisations. It typically only brings criminal proceedings as a last resort. If a criminal prosecution is brought, then the penalties depend on whether it is a summary offence (a lesser criminal offence heard before a magistrate with no jury) or an indictable offence (a more serious offence tried before a judge and jury). The maximum penalty on summary conviction under the HMR is a fine not exceeding £5,000 whereas on an indictment conviction the maximum penalties are an unlimited fine and/or imprisonment not exceeding 2 years.

The MHRA’s enforcement powers for noncompliance in relation to medical devices are wide ranging. The Consumer Protection Act 1987 allows it to issue prohibition notices to ban the supply of any goods which fail to comply with the relevant regulations, and it can also file suspension notices and forfeiture orders for non-compliant goods. Further, under the UK MDR, the MHRA can issue compliance notices and/or restriction notices to limit the availability of a particular device or devices of a particular class/description where they are non-conforming (e.g. no CE marking has been applied to them).

If a criminal prosecution is brought, the UK MDR states that for serious offences (such as failing to adhere to a notice) then the possible penalties include 6 months’ imprisonment and/or an unlimited fine.

Where it decides that there is an infringement of authorisation obligations, the European Commission can impose a penalty of up to 5% of the MAH’s EU turnover in the preceding business year, plus a daily penalty of a maximum of 25% of the MAH’s daily EU turnover for the preceding business year if the MAH does not cease infringing when ordered to. Lesser penalties of up to 0.5% of EU turnover apply where the MAH fails to comply with information requests or provides inaccurate or incomplete information.

 

10. Is there a national healthcare system? If so, how is it administered and funded?

The UK’s NHS is one of the largest publicly funded healthcare services in the world, although since 1999 administration has been devolved to the governments of the UK’s four constituent parts, giving rise to NHS England, NHS Scotland and so on. This answer focuses on NHS England.

The Secretary of State for Health, which is a cabinet position in the UK government, has overall responsibility for the provision of health services in England (as well as other health-related matters that have not been devolved). These responsibilities include financial control and oversight of all NHS England’s services. Below central government level the structure of NHS England is complex and based around Clinical Commissioning Groups (CCGs), which are directly responsible for commissioning hospital and community health services within their local area, and, since 2016, Sustainability and Transformation Partnerships (STPs). STPs are made up of local NHS bodies and local councils with the aim of running services in their area in a more coordinated way and to plan how to improve local residents’ health. STPs can evolve to become “Integrated Care Systems“, which are even closer forms of collaboration between the NHS and local councils with shared responsibility for resourcing and improving local health services.

The NHS is mainly funded from general taxation and National Insurance receipts (National Insurance is a specific tax paid by employers, employees and the self-employed and is used for funding state benefits). In addition, a small portion of NHS England’s funding is generated through patient charges such as those for prescriptions and dental care. NHS England’s budget for 2019/2020 is £121 billion, of which about 80% will come from general taxation.

 

11. How does the government (or public) healthcare system function with private sector healthcare?

Interactions between the public NHS and private healthcare enterprises are complex and controversial, although private companies and other bodies have always played a role within the NHS. For example, all dentistry and optometry services and pharmacy practices as well as most doctors’ practices are private and certain clinical services (such as radiology and pathology) are delivered through NHS/private enterprise partnerships.

As UK residents are entitled to universal healthcare the private medical insurance (PMI) sector is a niche market. PMI is typically provided as a part of benefit packages for higher-earning employees via monthly premiums. However, many PMI patients still use the NHS for non-emergency and/or routine concerns using the PMI to supplement their care/treatment (e.g. to get appointments with specialist consultants more quickly, for elective procedures or for more complicated health matters).

 

12. Are prices of drugs and devices regulated and, if so, how?

(i) Branded Medicines

As said in answer to Question 2, the price of branded medicines (prescription and non-prescription and including branded generics) is regulated through either the Voluntary Scheme or the Statutory Scheme.
The Voluntary Scheme arises from an agreement between the DHSC, NHS England, manufacturers and suppliers of branded medicines that have decided to join the scheme and the industry body, the Association of the British Pharmaceutical Industry (ABPI). The Voluntary Scheme has the aims of promoting innovation, public access to cost effective medicines and supporting sustainability of NHS finances. The key terms are that a scheme member wishing to launch a branded medicine on the UK market must give the DHSC at least 28 days’ written notice, with a proposed NHS list price. It cannot proceed with that launch until it has received confirmation that it has freedom of pricing (if the medicine is based on a new active substance) or that its proposed list price is acceptable (taking into account various factors including what the DHSC considers to be a reasonable profit). Even if the scheme member has free pricing, it must still set its price at a level consistent with obtaining a positive appraisal from the National Institute for Health & Care Excellence (NICE – the body that publishes guidance on clinical practice in the NHS). This effectively constrains the price and may require the scheme member to agree discounts with the NHS. Once set, the NHS list price cannot be increased without DHSC approval.

Other terms include, as part of an “affordability mechanism”, that the growth in the total annual cost of branded medicines to the NHS is capped at 2%, with any spending by the NHS over this limit being repaid by the industry (through a percentage payment to be made by each scheme member on their net sales, the percentage being 9.6% for 2019). However, this rebate does not apply to members with sales of scheme products of less than £5 million for the previous year or to sales of medicines based on new chemical entities.

In addition, the Voluntary Scheme places a limit on the reasonable profits that can be made by having a target for the allowable return on capital of 21%, subject to a margin of tolerance of 50%. This means that if a member’s profits exceed the 21% target by over 50%, it either has to repay the excess or reduce prices by an equivalent amount. Conversely, if its profits are more than 50% below the target, it can apply to increase prices.

The small percentage of companies that have not signed up to the Voluntary Scheme are automatically subject to the Statutory Scheme. This controls the maximum price of branded prescription-only medicines (POMs). It also requires companies to pay a percentage of their qualifying annual sales to the government in a similar manner to that under Voluntary Scheme (and, since the Statutory Scheme was introduced the payment percentages have been more closely aligned to those under the Voluntary Scheme). Companies with relevant sales of less than £5m per year are exempt from the price controls and the percentage payments.

(ii) Unbranded Generic Medicines & Medical Devices

See the answer to Question 2 above.

(iii) Over the Counter & Unlicensed Medicines

The price of over the counter (OTC) medicines (i.e. pharmacy-only and general sales list (GSL) medicines) is agreed between the manufacturer or wholesaler and the retailer (pharmacy, supermarket etc.).

Prescribers can prescribe unlicensed medicines except for those on the NHS’s blacklist (Part XVIIIA of the Drug Tariff), which are not permitted. In addition, medicines on the Selected List Scheme (Part XVIIIB of the Drug Tariff) can only be prescribed for the purposes given in the Drug Tariff. Prescriptions must be endorsed “SLS” by the prescriber. The prices in the Drug Tariff are set by analysis of a selection of unlicensed specials manufacturers’ prices, plus a margin for pharmacy purchase profit.

 

13. How are the drugs and devices used by patients paid for? What roles do public and private payers play?

(i) Medicines

Essentially, once a price for a licensed, prescription medicine has been set by the mechanisms discussed in the answers to Questions 2 and 12, and so is included in the NHS price list or Drug Tariff, pharmacists or doctors prescribing the medicines will be reimbursed the listed price by the NHS. The same applies to unlicensed medicines, save that prescriptions of blacklisted medicines or Selected List Scheme that are not endorsed “SLS” will not be reimbursed.

In addition, NHS England charges for prescriptions (£9.00 per prescription as from 1 April 2019) whereas NHS Wales, Scotland and Northern Ireland do not. However, prescriptions in England are free for a number of categories of persons including: children under 16, low income support individuals, pregnant women, persons over the age of 60 and other groups of individuals with valid medical exemptions. There is also the option of the Prescription Prepayment Certificate (PPC) for those who do not qualify for free prescriptions. The PPC entails a fixed amount payment for a 3 month or 12 month period irrespective of the number of prescriptions needed. It therefore provides a cost effective method of meeting prescription charges for those who need more than 1 prescription per month.

The above applies to primary care. As regards secondary care (e.g. within hospitals, clinics or similar), the NHS uses a payment by results model for reimbursement of the care provider, based on factors such as number of patients treated, the length of the patients’ stays and the nature and complexity of the treatment. The price of the medicines involved is not directly taken into account.

(ii) Medical Devices

Once a medical device has been CE marked, and approved by NICE, it can be listed in the British National Formulary (BNF). For reimbursement, though, CCGs need to decide to allow use of the device in hospitals and/or out of hospital in their region. Once a CCG decides that a BNF-listed device should be available, the NHS can reimburse its use.

 

14. Who dispenses drugs and devices to patients and how are those dispensers compensated?

The Medicines Act 1968 defines 3 legal categories of medicines: POMs, pharmacy medicines and GSL medicines.

POMs can only be sold by a pharmacy registered with the General Pharmaceutical Council (GPhC), under the supervision of a responsible pharmacist, and pursuant to a valid prescription given by an authorised practitioner (these requirements apply even when the sale or supply is made via the internet). The responsibilities of the responsible pharmacist are set out in the Medicines (Pharmacies) (Responsible Pharmacist) Regulations 2008 (discussed further in answer to Question 15) and he/she must be registered with the GPhC. A corporate body running a registered pharmacy or pharmacies must also nominate a registered pharmacist to act as superintendent pharmacist with overall management of the pharmacy. The responsible and superintendent pharmacist can be the same person (though where a company runs several pharmacies, it will not be possible for one person to meet both sets of legal duties).
The same rules apply to the sale and supply of pharmacy medicines (save that they are not sold pursuant to prescriptions).

GSL medicines can be sold from any premises so long as they are pre-packed and the premise can be locked from the public (and, if sold from a machine, that machine must be within such premises).
The reimbursement of pharmacies for drugs and devices supplied by them has been discussed in the answers to Questions 2 and 13. In addition, pharmacies can claim certain fees and allowances from NHS England for dispensing certain products under Part IIIA of the Drug Tariff (which covers professional fees).

 

15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?

As said in answer to Question 14, a pharmacy business must appoint a registered pharmacist to act as the responsible pharmacist. The responsible pharmacist’s role is to secure the safe and effective running of the registered pharmacy at all times that he/she is in charge (i.e. including when the pharmacy is operating but not open to the public or when absent on pharmacy business). In particular, the role includes responsibility for the sale and supply of all medicines from the pharmacy. The duties include:

• displaying a conspicuous notice that gives the details of who the responsible pharmacist is;
• making and keeping records;
• following pharmacy procedures; and
• making appropriate arrangements for periods when absent from the pharmacy.

 

 

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Click the following links to read more legal articles from United Kingdom:

1. Regulatory Pricing and Reimbursement Overview
2. Preclinical and Clinical Trial Requirements
3. Marketing, Manufacturing, Packaging & Labeling, Advertising
4. Traditional Medicines and OTC Products
5. Product Liability
6. Patents & Trademarks
7. Regulatory Reforms