Commercialisation of healthcare in the UK (England and Wales): overview

A Q&A guide to the commercialisation of healthcare in the UK (England and Wales).

This Q&A provides an overview of the regulatory framework for the commercialisation of medical products in the UK (England and Wales). It covers the key requirements for manufacturing, advertising and selling drugs, medical devices, biological products and natural health products.

To compare answers across multiple jurisdictions, visit the commercialisation of healthcare Country Q&A tool.

This Q&A is part of the Commercialisation of Healthcare Global Guide. For a full list of jurisdictional Q&As visit www.practicallaw.com/healthcare-guide.

Contents

Regulatory overview

1. What is the regulatory framework for medical products?

Legislation

Much of the UK regulatory framework for medical products derives from EU legislation. The two main categories of medical products are medicinal products and medical devices.

For medicinal products, the key EU legislation is:

  • Directive 2001/83/EC on the Community code relating to medicinal products for human use (Community Code), as amended and implemented into national UK law.

  • Regulation (EC) No 726/2004 on the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (EMA Regulation), as amended.

The main UK legislation is the Human Medicines Regulations 2012 (HMRs), which implement EU legislation, including the Community Code, into UK law. The HMRs also regulate areas where the UK can set its own national level requirements, such as the conditions under which unlicensed medicines can be supplied.

The definition of "medicinal product" in the HMRs reflects the definition in the Community Code, which, in summary, is a substance that is either:

  • Presented as preventing or treating disease.

  • Used to correct or modify a physiological function by pharmacological, immunological or metabolic action, or to make a medical diagnosis.

Detailed guidance on the requirements set out in the legislation is issued by a number of bodies, including the European Commission, the European Medicines Agency (EMA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

The EU and UK regulatory framework for medical devices is different from that for medicinal products. Currently (although see Question 24), the key EU medical device legislation is:

  • Directive 93/42/EEC concerning medical devices (Medical Devices Directive).

  • Directive 90/385/EEC on active implantable medical devices (Active Implantable Medical Devices Directive).

  • Directive 98/79/EC on in vitro diagnostic medical devices (IVD Directive).

The UK Medical Devices Regulations 2002 implement the three EU medical device directives into national law. The definition of "medical device" in the Medical Devices Regulations reflects the definition in the Medical Devices Directive. In summary, it is an instrument or other article that both:

  • Is intended to be used to diagnose, prevent, monitor or treat disease or an injury, or to investigate or modify the anatomy or a physiological process.

  • Does not principally work by a physiological function, by pharmacological, immunological or metabolic action.

Detailed guidance on the requirements set out in medical devices legislation is also issued by a number of bodies, including the European Commission, the EMA and the MHRA. UK consumer protection legislation and codes of practice are also relevant as, for example, these govern the advertising of medical devices (see Question 12).

Regulatory authorities

The UK national competent authority for both medicinal products and medical devices is the MHRA, which is an executive agency of the UK Government's Department of Health. The Department of Health also oversees the pricing and reimbursement of medicines used in the National Health Service, with input from health technology assessment bodies, such as the National Institute for Health and Care Excellence.

The EMA is responsible for the scientific evaluation of applications for EU-wide marketing authorisations for medicinal products (see Question 3, Sale ). These are granted by the European Commission, based on the opinion of the EMA.

For more information on the EMA and MHRA see box: The regulatory authorities.

Private parties

There are a number of non-governmental bodies that are involved in the regulation of advertising and promotion of medicines and medical devices. These include the Advertising Standards Authority (ASA), which is an independent body, and various industry associations, for example the:

  • Association of the British Pharmaceutical Industry (ABPI) and the Prescription Medicines Code of Practice Authority (PMCPA) which enforces the Code.

  • Proprietary Association of Great Britain (PAGB).

  • Association of British Healthcare Industries (ABHI).

  • British Healthcare Trades Association (BHTA).

For more information on the role of these bodies in the regulation of advertising and promotion, please see Question 7 on medicinal products and Question 12 on medical devices.

 
2. What types of medical products are regulated?

The following types of medical products are regulated:

  • Medicinal products. These are regulated under medicinal products legislation and include biological products, traditional herbal medicines and homeopathic medicines.

  • Medical devices. These are regulated under separate medical devices legislation.

  • Other medical products. Products falling outside the definition of a medicinal product or a medical device (for example, digital health applications that fall outside the scope of the medical devices legislation) are regulated under general product safety and consumer protection legislation.

  • Food supplements. These are regulated under food legislation.

 

Drugs

3. What are the general requirements for a drug to be manufactured, advertised and sold?

Every stage in the life cycle of a medicine is regulated, including development, manufacture, distribution, advertising and sales.

Manufacturing

A manufacturer's licence issued by the Medicines and Healthcare Products Regulatory Agency (MHRA) is required in order to manufacture, assemble and/or import a medicinal product.

To be granted a manufacturer's licence, a manufacturer must demonstrate that it complies with EU good manufacturing practices (GMP) requirements. It must also pass regular good manufacturing practices site inspections by the MHRA.

The principles of good manufacturing practices for medicinal products are set out in:

  • Directive 2001/83/EC on the Community code relating to medicinal products for human use (Community Code), as amended.

  • Directive 2003/94/EC on good manufacturing practice for medicinal products (GMP Directive).

In summary, the manufacture of a medicinal product must be of consistent high quality and consistent with the specifications set out in the marketing authorisation. The European Medicines Agency (EMA) and MHRA have both published detailed guidance on complying with good manufacturing practices.

Different types of manufacturer's licences are available depending on the specific activities carried out by the manufacturer and the status of the product. For example, a manufacturer's "specials" licence is required to manufacture unlicensed medicinal products or import unlicensed medicinal products from outside the European Economic Area (EEA). A manufacturer's licence for investigational medicinal products is required to make unlicensed medicinal products for use in clinical trials.

An application for a manufacturer's licence must be submitted to the MHRA using its application form. The MHRA will assess the application and aims to process applications, including carrying out a site inspection, within 90 working days. Variations to a manufacturer's licence are generally processed within 30 working days (or 90 working days if an inspection is required).

Advertising

A medicinal product must have a valid marketing authorisation before it can be advertised in the UK.

Advertising medicines to both healthcare professionals and the general public is highly regulated through a combination of legislation (Part 14 of the Human Medicines Regulations 2012 (HMRs), which implements Title VIII of the Community Code), MHRA guidance and industry self-regulatory codes of practice.

One of the key restrictions is that marketing authorisation holders are not allowed to advertise prescription-only medicinal products to members of the public.

See Question 7 for further details.

Sale

In order to place a medicinal product on the market and sell it in the UK, that product must have a valid marketing authorisation.

To obtain a marketing authorisation, a competent authority must assess the product to ensure that it meets the necessary safety, quality and efficacy criteria. These are set out in the:

  • Community Code.

  • HMRs.

  • Regulation (EC) No 726/2004 on the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (EMA Regulation), as amended.

The two main procedures for obtaining a marketing authorisation are the:

  • Centralised procedure, which results in a marketing authorisation granted by the European Commission and is valid throughout the European Economic Area (EEA).

  • National procedure, which results in a marketing authorisation issued by the MHRA and is valid in the UK only.

A UK national authorisation can be obtained independently or as part of an application for national authorisations in multiple EU member states. If there is no existing marketing authorisation in any member state, the decentralised procedure is used. If a national marketing authorisation has already been granted by another member state, the mutual recognition procedure is used.

Certain types of medicinal products must be authorised through the centralised procedure, such as new active substances for the treatment of cancer, diabetes or HIV/AIDS. Subject to EMA approval, certain other products (such as those with a significant therapeutic, scientific or technical benefit) can also be authorised through the centralised procedure. All other medicinal products must be authorised using the national procedure, decentralised procedure or mutual recognition procedure.

To apply for a marketing authorisation, the applicant must be established within the EEA. Applications for both a centralised authorisation and national authorisation must contain details of pre-clinical and clinical testing, mock-ups of the "summary of product characteristics" (SmPC), labelling and packaging, and must be provided in a set format called the "electronic common technical dossier" (eCTD). Further detailed requirements are set out in the Community Code, the EMA Regulation and the European Commission's Notice to Applicants guidance documents.

The application process for both a centralised authorisation and national authorisation is broadly similar. Once the application has been submitted to and validated by the relevant regulator (the EMA or MHRA, as applicable), it is assessed and, if the assessment is positive, a marketing authorisation is granted (by the European Commission in the centralised procedure or by the MHRA in the national procedure). The timetable for the MHRA to grant or refuse a national marketing authorisation application is 210 days from validation of the application. However, if the MHRA requests further information from the applicant, the process will take longer.

Once a marketing authorisation is granted, if a medicinal product is not actually placed on the market within three years, the authorisation will no longer be valid. This also applies where, after being authorised and placed on the market, a medicinal product is taken off the market for a period of three consecutive years.

Marketing authorisations are valid for an initial term of five years. Once renewed, the authorisation is usually then valid indefinitely, unless there are specific safety concerns, in which case the EMA/MHRA can require one further renewal period of five years.

Any subsequent changes to a marketing authorisation, such as a change in the manufacturing process or an extension to the indication, must be submitted through a prescribed variations procedure.

In the UK, there is a limited exception to the requirement for a medicinal product to have a marketing authorisation, known as "named patient" supply. In certain circumstances, patients can be prescribed and supplied with products that are not licensed in the UK. The conditions that must be met in order to supply an unlicensed medicine on a named patient basis are set out in Part 10 of the HMRs.

In addition, in 2014, the MHRA introduced a voluntary "early access to medicine scheme" (EAMS) to help give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a UK or EU marketing authorisation. This is for cases where there is a clear unmet medical need. Applicants first apply to the MHRA for the product to be designated as a "promising innovative medicine" (PIM). If the product meets the criteria, the MHRA then issues a scientific opinion on the risk/benefit balance of the medicine, which is intended to help healthcare professionals evaluate whether it is clinically appropriate to prescribe for a particular patient off-label.

Anyone that distributes or otherwise supplies medicines must hold a wholesale dealer's licence from the MHRA. Where a company or other entity brokers the sale of medicines (that is, arranges sales on behalf of another entity) but is not itself wholesale dealing, the broker must register with the MHRA.

 
4. Are there different requirements for patented and generic drugs?

Both patented and generic medicinal products require a marketing authorisation before they can be placed on the market. However, the information that must be provided in the marketing authorisation application for such products differs slightly.

For a new medicinal product (innovator product), a full marketing authorisation application dossier must be submitted, containing pre-clinical and clinical trial data. Once the marketing authorisation has been granted, the medicinal product benefits from a period of data and market exclusivity. To protect developers of innovator products, Directive 2001/83/EC on the Community code relating to medicinal products for human use (Community Code), as amended, sets out the "8+2+1" rule. Historically there were different exclusivity periods in different EU countries which, under the transitional arrangements may still apply to a limited number of products authorised before the introduction of the harmonised exclusivity period.

During the data exclusivity period, an applicant for a marketing authorisation for a generic product cannot submit their application until after the eighth anniversary of the innovator product's authorisation. Regardless of when the generic application is granted, the generic medicinal product cannot be marketed for a further two years (until after the tenth anniversary of the innovator product's authorisation). An additional year of market exclusivity applies if the innovator obtains approval for a new indication which brings significant clinical benefit in comparison to existing technologies during the first eight years of the product's data exclusivity period. Data and market exclusivity are separate from patent rights.

Generic products have the same active substance and pharmaceutical form as the reference innovator product. An applicant for a marketing authorisation for a generic medicinal product can use an abridged application process. This means the generic application must meet the same safety, efficacy and quality standards, but the applicant is not required to repeat clinical testing to prove the product's efficacy and safety. Instead, the generic applicant can cross-refer to the clinical trial data in the reference product's dossier to demonstrate product efficacy and safety. However, the generic applicant must prove that the generic medicinal product is bioequivalent to the reference medicinal product.

 
5. What authority is responsible for regulating the manufacture, advertising and sale of drugs?

The Medicines and Healthcare Products Regulatory Agency (MHRA) is the national competent authority responsible for regulating the manufacture, advertising and sale of medicinal products including:

  • Granting manufacturers' and wholesale dealers' licences.

  • Reviewing marketing authorisation applications for placing medicinal products on the UK market.

  • Monitoring and enforcing medicinal product advertising.

The competent authority of the EU member state in which the products are manufactured, advertised or sold is responsible for the conduct of those activities in that territory.

For more information on the MHRA see box: The regulatory authorities.

 
6. Are there fewer or different requirements for drugs that have already been licensed/approved in another jurisdiction?

If a medicinal product has received a marketing authorisation through the centralised procedure, it can be marketed freely in any member state of the European Economic Area (EEA), including the UK. No additional permission from the Medicines and Healthcare Products Regulatory Agency (MHRA) is necessary.

If a medicinal product has been approved in another EU (or EEA) member state, the marketing authorisation holder can apply to the MHRA for a UK national authorisation through the mutual recognition procedure.

A medicinal product that has been approved in a jurisdiction outside the EEA must obtain a relevant EU or national marketing authorisation before it can be placed on the market in the UK. The application requirements for such products are not reduced. However, the electronic common technical dossier format and content has been agreed between the EU, US and Japan (with the exception of Module 1 which contains region-specific information) to facilitate the submission of applications across these regions.

 
7. Is it possible to sell drugs to or buy drugs from other jurisdictions?

The requirements for importing or exporting medicinal products differ depending on whether the medicinal product will be transferred within or outside the European Economic Area (EEA) and whether it has a marketing authorisation or not.

The Medicines and Healthcare Products Regulatory Agency's (MHRA's) parallel import licensing scheme allows a medicinal product that is authorised in another EEA member state to be imported in to the UK, provided that the imported product has no therapeutic difference from an equivalent product that is already authorised in the UK. To make a parallel import, an importer must:

  • Ensure the medicinal product was manufactured according to good manufacturing practices standards.

  • Hold an MHRA wholesale dealer's licence.

  • Hold the correct type of MHRA parallel import licence.

An importer wishing to import a licensed medicinal product from outside the EEA needs an MHRA manufacturer's licence. The licence holder must have a qualified person to ensure that each production batch has undergone the correct analysis and checks. Where a batch of medicinal product has been imported from Australia, Canada, New Zealand or Switzerland (countries that have signed a mutual recognition agreement with the EU), then full re-testing of the batch in the UK is not required.

An importer wishing to import an unlicensed medicinal product into the UK from within the EEA requires an MHRA wholesale dealer's licence.

An importer wishing to import an unlicensed medicinal product from outside the EEA requires a manufacturer "specials" licence. Any importer intending to import an unlicensed medicinal product (whether from inside or outside the EEA) must send the MHRA a completed notification of intent form 28 days before the product is imported.

In order to export a medicinal product outside the EEA, a manufacturer requires an MHRA manufacturer's licence. Where the exporter is not the manufacturer of the medicinal product, they require an MHRA wholesale dealer's licence to export the product. It is not possible to export unlicensed medicinal products ("specials") outside the EEA.

Additionally, the destination country may require an export certificate, which can be obtained from the MHRA.

 
8. Is it permitted to advertise drugs to consumers? Are there restrictions on advertising?

As in other EU member states, prescription-only medicines (POMs) cannot be advertised to the general public in the UK. POMs can be advertised to healthcare professionals who are qualified to prescribe or supply medicines, subject to complying with the detailed advertising rules below.

In the UK, over-the-counter (OTC) medicines are split into two categories, general sales list (GSL) products and pharmacy-only (P) products. OTC medicines can be advertised to both the general public and healthcare professionals, subject to complying with detailed advertising rules.

Advertising is defined widely as anything designed to promote the prescription, supply, sale or consumption of medicinal products. It includes:

  • Print, website and broadcast materials.

  • Medical sales representatives' activities.

  • Product samples, gifts and hospitality.

  • Sponsorship of promotional meetings and scientific congresses attended by healthcare professionals.

The definition of advertising does not include:

  • The packaging, summary of product characteristics and patient information leaflet of a medicine.

  • Factual reference material, trade catalogues and price lists (provided that no product claim is made).

  • Information about diseases where there is no reference to medicinal products.

  • Non-promotional responses to unsolicited questions about a medicine.

The advertising of medicinal products in the UK is controlled by a combination of legislation and industry self-regulation through codes of practice. The key UK legislation and codes include the:

  • Human Medicines Regulations 2012 (HMRs).

  • Medicines and Healthcare Products Regulatory Agency (MHRA) Blue Guide on Advertising, which contains guidance on the interpretation of the legal standards expected when advertising and promoting medicines.

  • Association of the British Pharmaceutical Industry Code (ABPI Code), which governs the advertising of prescription-only medicines to healthcare professionals and the provision of non-promotional information about prescription-only medicines to both healthcare professionals and the public. The ABPI Code implements the European Federation of Pharmaceutical Industry Associations (EFPIA) Code.

  • Proprietary Association of Great Britain (PAGB) codes of practice (one for consumers and one for healthcare professionals). These apply to all branded promotional materials for over-the-counter medicinal products (that is, both pharmacy-only and general sales list products).

The HMRs and MHRA Blue Guide apply to all advertisers of medicines. Compliance with the ABPI and PAGB Codes is only a requirement for members of the ABPI and PAGB, respectively. The majority of major pharmaceutical companies in the UK have signed up to these codes.

The key principles for advertising an over-the-counter medicine to consumers include that the:

  • Product must have a marketing authorisation valid in the UK and can only be promoted in accordance with particulars listed in the summary of product characteristics. For example, any advertisement must not promote the product outside the indication(s) stated in the summary of product characteristics.

  • Advertisement must encourage the correct and proper use of the product by presenting it objectively and without exaggeration.

  • Advertisement must not be misleading.

 

Medical devices

9. What are the general requirements for a medical device to be manufactured, advertised and sold?

Manufacturing

A manufacturer of a medical device does not require a specific manufacturing licence in the UK. Instead, the manufacturer must ensure that its medical device is manufactured in accordance with the essential requirements set out in the relevant medical devices directive (see Question 1, Legislation).

Advertising

A medical device can only be advertised if it has been CE marked (see below, Sale) and can only be promoted for the intended purposes for which it has been CE marked.

See Question 12 for further details.

Sale

A manufacturer of a medical device is not required to obtain a pre-market authorisation for their device from the Medicines and Healthcare Products Regulatory Agency (MHRA) or European Medicines Agency (EMA) in the same way as for a medicinal product.

However, before a medical device can be sold in the UK (or anywhere in the EU), it must be CE marked. CE marking is a declaration by the manufacturer that the device meets the essential requirements set out in the relevant medical devices directive, which vary depending on the type and classification of the device.

The first step in the process of CE marking a device is for the manufacturer to classify their medical device. Medical devices are divided into Class I, Class IIa, Class IIb and Class III devices. Class I devices represent the lowest risk and Class III devices the highest risk. Classification is based on factors such as the intended purpose of the device, its duration of use, the invasiveness of the device and where the device is used.

Once classified, a medical device must meet the essential requirements applicable to that class of device, as set out in Annex I of the relevant medical devices directive. Compliance with the essential requirements is presumed if the medical device conforms to an appropriate harmonised European standard.

The manufacturer must carry out the appropriate conformity assessment procedure, which again varies depending on the class of the device. For example, a manufacturer of a Class I medical device self-certifies that the device complies with the applicable essential requirements and then CE marks the product. The conformity of Class IIa, Class IIb, or Class III medical devices (and certain Class I devices, for example those with a measuring function) must be assessed by a "notified body". A notified body is a public or private organisation that has been designated by an EU member state to assess whether manufacturers and their medical devices meet the applicable essential requirements. A list of UK notified bodies for medical devices is available from the MHRA. Following the assessment, the notified body will issue a CE certificate of conformity enabling the manufacturer to affix the CE mark to the product.

A CE marked medical device can be marketed freely throughout the EU/ European Economic Area (EEA). However, some registration or notification requirements may be imposed on the manufacturer, its European authorised representative or the distributor of the medical devices in the relevant countries. For example, before placing a self-certified medical device (that is, a Class I, custom-made or sterile device) on the UK market, the manufacturer or its European authorised representative established in the UK must register with the MHRA, providing details of their place of business and a description of the medical device.

 
10. What authority is responsible for regulating the manufacture, advertising and sale of medical devices?

The Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for regulating the manufacture and sale of medical devices in the UK.

The advertising of medical devices is regulated under consumer protection law and codes of practice, for which Trading Standards and the Advertising Standards Authority are responsible respectively.

See Question 12 for further details.

 
11. Are there fewer or different requirements for medical devices that have already been licensed/approved in another jurisdiction?

A CE marked medical device marketed anywhere in the EU/ European Economic Area (EEA) can be marketed in the UK without any further approval from the Medicines and Healthcare Products Regulatory Agency (MHRA).

A medical device approved in a third country (that is, outside the EEA) must undergo a conformity assessment and be CE marked in accordance with the full requirements of the relevant medical devices directive (see Question 1) before it can be sold within the EU/EEA.

 
12. Is it possible to sell devices to or buy devices from other jurisdictions?

A CE marked medical device can be sold or bought anywhere in the EU/ European Economic Area (EEA).

A person who is not the manufacturer of a medical device and imports a CE marked medical device from within the EU/EEA is known as a parallel importer. A parallel importer can be regarded as the manufacturer of the device if they either:

  • Repackage and rebrand the device.

  • Change the device so that it is no longer covered by the original CE mark.

A parallel importer that is deemed to be the manufacturer of the device will need to carry out a new conformity assessment procedure before the device can be CE marked and put on the market.

A medical device imported from outside the EEA must undergo a conformity assessment. It must be CE marked in accordance with the full requirements of the relevant medical devices directive (see Question 1, Legislation) before it can be sold in the UK.

A licence from the Medicines and Healthcare Products Regulatory Agency (MHRA) is not required to import, export or wholesale deal in medical devices.

 
13. Is it permitted to advertise medical devices to consumers? Are there restrictions on advertising?

Medical devices can be advertised directly to consumers. However, the device must be CE marked and can only be promoted for its intended purpose(s) as set out in its labelling, instruction for use and technical file.

Unlike some other EU member states, in the UK there is no specific legislation governing the advertising and promotion of medical devices. Advertising of medical devices is instead subject to the general rules relating to the advertising of consumer products in the UK. Advertising in the UK is controlled by a combination of legislation and self-regulatory codes of practice. These include the:

  • Consumer Protection from Unfair Commercial Practices Regulations 2008 (CPRs), which prohibit unfair commercial practices (including making misleading claims generally).

  • Business Protection from Misleading Marketing Regulations 2008 (BPRs), which include rules on making comparative claims.

  • UK Code of Non-broadcast Advertising, Sales Promotion and Direct Marketing (CAP Code).

  • UK Code of Broadcast Advertising (BCAP Code).

The CAP Code covers most non-broadcast advertisements relating to medical devices. However, claims addressed only to medical practitioners that relate to their expertise are expressly excluded from its remit on the basis that professionals have a different level of understanding of such claims than the general public. Such claims are still subject to the legislation set out above. The CAP Code applies to claims made to consumers and claims about the non-health-related characteristics of a product (for example, performance) made to healthcare professionals.

The key principles of the CAP and BCAP Codes include that all marketing communications must:

  • Be legal, honest and not misleading (nor likely to mislead).

  • Be prepared with a sense of responsibility to consumers.

  • Not encourage unsafe practices.

The CAP and BCAP Codes also contain specific rules on the advertising of health products. Advertisers must not discourage essential treatment or offer advice on diagnosis of or treatment for serious or prolonged conditions, unless it is conducted under the supervision of a doctor or other suitably qualified health professional.

The Association of British Healthcare Industries (ABHI) has also developed a Code of business practice (ABHI Code) that specifically covers advertisements for medical devices addressed primarily to healthcare professionals. The British Healthcare Trades Association (BHTA) publishes the BHTA Code of Business Practice which covers advertising and sales of healthcare and assistive technology products and services. The ABHI and BHTA Codes are only binding on their members and other companies who have agreed to abide by them.

 

Biological products

14. What are the general requirements for a biological product to be manufactured, advertised and sold?

A "biological medicinal product" is a medicinal product containing a human or animal derived active substance, for example a protein, enzyme or antibody.

Biological medicinal products are regulated in the same way as non-biological medicinal products (see Question 3). Valid manufacturing and wholesale dealing licences and a marketing authorisation are required in order to manufacture, distribute, advertise and sell a biological medicine.

Certain biological medicines must be authorised using the centralised procedure, including:

  • Biotechnology products (for example, hybridoma and monoclonal antibodies, products developed using recombinant DNA technology and products manufactured using controlled expression of genes coding for biologically active proteins).

  • Advanced therapy products (gene and somatic cell therapy and tissue engineered products).

There are additional information requirements for marketing authorisation applications for biological medicinal products. For example, in an application dossier concerning a plasma-derived medicinal product, the information relating to the starting and raw materials must be replaced with a "plasma master file". In an application dossier for a vaccine, the dossier must include a "vaccine antigen master file".

Products that are similar to another biological medicinal product that has already been authorised for use are known as "similar biological medicinal products" or "biosimilars" and not as "generics". This reflects the complexity of manufacturing a biological medicine, meaning that it can be difficult to precisely replicate the raw materials and manufacturing processes involved.

There is a specific authorisation route for biosimilars. Biosimilars cannot be authorised using the abridged application available to small molecule generic medicines. An applicant for a biosimilar marketing authorisation must carry out additional studies to show that the biosimilar is similar to the original (reference) biological medicinal product and that it does not have any meaningful differences from it in terms of quality, safety and efficacy.

For biosimilars where the reference product is authorised through the centralised procedure, the biosimilar is automatically eligible to be authorised through the centralised procedure as well. Where the reference product is authorised through the national procedure, the mutual recognition procedure or the decentralised procedure, the biosimilar may be eligible to be authorised through the centralised procedure if the applicant can demonstrate either:

  • That the biosimilar is a significant therapeutic, scientific or technical innovation.

  • That the granting of an EU marketing authorisation is in the interest of patients at EU level.

The data and market exclusivity periods described in Question 4 also apply to biosimilars.

 
15. What authority is responsible for regulating the manufacture, advertising and sale of biological products?

The authorities responsible for regulating the manufacturing, advertising and sale of biological products are the same as for medicinal products generally (see Question 5).

 
16. Are there fewer or different requirements for biological products that have already been licensed/approved in another jurisdiction?

The position for biological products is the same as for medicinal products generally (see Question 6).

 
17. Is it possible to sell biological products to or buy biological devices from other jurisdictions?

The position for biological products is the same as for medicinal products generally (see Question 7).

 
18. Is it permitted to advertise biological products to consumers? Are there restrictions on advertising?

The position for biological products is the same as for medicinal products generally (see Question 8).

 

Natural health products

19. Is there a category for natural health products (including, for example, traditional medicines, homeopathic medicines, supplements, vitamins and minerals)?

"Natural health products" can fall under any one of a number of different legal categories. Traditional herbal medicines and homeopathic medicines are regulated as medicinal products. Supplements, including vitamins and minerals, that fall outside the definition of a medicine (that is, which do not have, and are not presented as having, a medicinal effect) are regulated as "food supplements" under food legislation.

 
20. What are the general requirements for natural health products to be manufactured, advertised and sold?

Manufacturing

Manufacturers of traditional herbal medicines and homeopathic medicines are also required to be licenced by the Medicines and Healthcare Products Regulatory Agency (MHRA) and comply with EU good manufacturing practices.

A licence is not required to manufacture food supplements but the manufacturer must be satisfied that the manufacture of the product complies with all relevant food and food supplement safety legislation. Food manufacturing premises are inspected by the Foods Standards Agency (FSA).

Advertising

See Question 23.

Sale

Traditional herbal medicines and homeopathic medicines must be approved before being placed on the market in the EU.

Traditional herbal medicines can be approved either through a simplified registration process or a full marketing authorisation process, depending on the exact nature of the product and the claims made. Clinical trials demonstrating the efficacy of a traditional herbal medicine are not required if the product can be shown to have been in safe, continuous use for at least 30 years (Directive 2004/24/EC on traditional herbal medicinal products, as implemented through the Human Medicines Regulations 2012). To register a traditional herbal medicine under the simplified registration process, the applicant must provide evidence confirming that the product:

  • Is made to good manufacturing practice quality standards.

  • Has appropriate labelling and a patient information leaflet.

  • Has been traditionally used to treat the stated condition for a minimum of 30 years, at least 15 of which must have been in the EU.

Only certain indications are permitted for registered traditional herbal medicines. The MHRA has published guidance on the types of indications that are and are not likely to be acceptable for traditional herbal medicines.

There are three licensing schemes for homeopathic medicines under which such products must meet set standards of safety and quality but are not required to demonstrate efficacy:

  • Product licences of right (PLRs) were issued to all medicinal products on the market in 1971 and are allowed to include therapeutic indications.

  • The simplified registration scheme, which was introduced in 1992, under which registered products are not allowed to include indications.

  • The national rules scheme, which was introduced in 2006, under which homeopathic products can be granted a marketing authorisation for the relief or treatment of mild, self-limiting conditions (which can generally be treated without medical supervision).

All homeopathic products must be licensed under one of the three schemes. The MHRA encourages companies to re-register PLR products in one of the two newer schemes.

Food supplements do not require pre-market approval but manufacturers must be satisfied that the product complies with all relevant food and food supplement safety and labelling legislation before placing it on the UK market.

 
21. What authority is responsible for regulating the manufacture, advertising and sale of natural health products?

The Medicines and Healthcare Products Regulatory Agency (MHRA) regulates herbal medicines and homeopathic medicines.

Responsibility for food supplement products is split across the Food Standards Agency (FSA), the Department of Health (DoH) and the Department for the Environment and Rural Affairs (DEFRA). The FSA is responsible for food safety, DEFRA is responsible for general labelling and the DoH is responsible for nutrition labelling.

 
22. Are there fewer or different requirements for natural health products that have already been licensed/approved in another jurisdiction?

A traditional herbal medicine or homeopathic medicine that has been approved in another jurisdiction must obtain the relevant pre-approval before it can be sold in the UK. The application requirements for such products are not reduced.

For food supplements, products that are legally compliant with the requirements in another EU member state can be marketed in the UK, provided that the mandatory labelling information is provided in English. Food supplement products from jurisdictions outside the EU/ European Economic Area (EEA) must comply with UK requirements before they can be sold in the UK.

 
23. Is it possible to sell natural health products to or buy natural health products from other jurisdictions and/or electronically?

An importer wishing to import traditional herbal medicines or homeopathic medicines from within the European Economic Area (EEA) will require a wholesale dealer licence from the Medicines and Healthcare Products Regulatory Agency (MHRA). A wholesale dealer licence is also required to export traditional herbal medicines or homeopathic medicines. For further information see Question 6.

An importer wishing to import traditional herbal medicines or homeopathic medicines from outside the EEA will require a manufacturer's licence. The traditional herbal medicine or homeopathic medicine must obtain the relevant pre-approval before it can be sold in the UK or online.

Traditional herbal medicines and homeopathic medicines can be sold online if they comply with the same sales and advertising requirements outlined above for products not sold online.

For food supplements, products can be bought or sold from other jurisdictions and/or electronically, provided that the products meet UK food supplement requirements. For food supplements sold online, all of the mandatory labelling information (except the best before date) must be provided to consumers before purchasing the product.

 
24. Is it permitted to advertise natural health products to consumers? Are there restrictions on advertising?

Advertising traditional herbal medicines, homeopathic medicines and food supplements to consumers is permitted.

The general rules on advertising any over-the-counter medicines to consumers also apply to traditional herbal medicines. In addition, specific rules on advertising products that are registered under the traditional herbal medicines scheme are set out in the Human Medicines Regulations 2012 (HMRs) and Appendix 1 of the MHRA's Blue Guide. These include that an advertisement for a traditional herbal medicine must include the sentence: "Traditional herbal medicinal product for use in [include one or more indications for the product from its registration] exclusively based upon long-standing use as a traditional remedy". It must not claim or imply that the effectiveness of that traditional herbal medicine has been demonstrated, for example, by using claims such as "clinically proven" or "effective in". Various industry bodies have also published relevant guidance and self-regulatory codes of practice, including the Proprietary Association of Great Britain (PAGB) and the British Herbal Medicine Association (BHMA).

For homeopathic medicines, the rules applicable to advertising are set out in the HMRs, Appendix 2 of the MHRA's Blue Guide and MHRA Guidance Note 17, and vary depending on which licensing scheme the product is regulated under (see Question 19). All advertisements for a homeopathic medicine must be based on its traditional use and must not claim or imply that the use of that medicine is based on clinical evidence or that its effectiveness has been demonstrated.

Advertising of food supplements is subject to the general UK advertising rules applicable to consumer products, which include that any claims must be true, not misleading and substantiated. There are also food-specific rules, such as Regulation (EC) 1924/2006 on nutrition and health claims made on foods (Nutrition and Health Claims Regulation), which restricts the claims that can be made in relation to the nutritional properties and health benefits of food products, including food supplements.

 

Reform

25. Are there any plans to reform the rules on the development, manufacture, advertising and sale of medical products?

Plans to reform UK rules on medical products typically derive from EU developments. For example:

  • From 1 July 2015, any UK-based retailer selling medicines to the public online must be registered with the Medicines and Healthcare Products Regulatory Agency (MHRA). It must also display the EU common logo, together with a hyperlink to the retailer's entry in the MHRA list of registered retailers, on every webpage that offers medicines for sale. Registered pharmacies can sell over-the-counter medicines or dispense prescription-only medicines against a prescription. All other general retailers can only sell general sales list medicinal products. In addition, the medicines being offered online must be licensed in the EU member state where the consumer purchasing the medicine is based.

  • Clinical trials of medicines in the EU are currently regulated by Directive 2001/20/EC on the conduct of clinical trials (Clinical Trials Directive). However, on 16 June 2014, Regulation (EU) No 536/2014 on clinical trials (Clinical Trials Regulation) entered into force and will take effect across the EU, including the UK, on the later of 28 May 2016 or six months after notification in the Official Journal of the European Union that the EU clinical trials portal and database are fully functional. The aims of the new Clinical Trials Regulation include streamlining the application procedure for clinical trials conducted in the EU, particularly for multi-site trials, and increasing transparency of clinical trial data.

  • There is ongoing reform regarding EU medical devices legislation. The European Commission has adopted a proposal for two regulations, the first on medical devices and the second on in vitro diagnostic medical devices. These regulations, once agreed and adopted, will replace the three current medical devices directives. Changes that will be introduced by the new regulations include clearer and greater powers for notified bodies, improved traceability of devices in the supply chain, increased vigilance requirements and a new requirement for manufacturers to have a "qualified person" responsible for regulatory compliance. The new regulations will have direct effect in EU member states and are intended to improve harmonisation. The powers of notified bodies will be clarified and increased across the EU, are likely to be finalised by early 2016 and would be introduced gradually over a transition period.

 

The regulatory authorities

European Medicines Agency (EMA)

W www.ema.europa.eu/ema/

Principal responsibilities. The EMA is a decentralised agency of the EU. It is responsible for the protection and promotion of public health, through the evaluation of medicines developed for use in the EU. Its activities include the scientific evaluation of applications for EU marketing authorisations through the centralised procedure, carrying out inspections in connection with such applications and co-ordinating the EU safety monitoring (pharmacovigilance) system for medicines.

Medicines and Healthcare Products Regulatory Agency (MHRA)

W www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency

Principal responsibilities. The MHRA is an executive agency of the Department of Health and is the national competent authority for the UK. The MHRA's responsibilities include:

  • Ensuring that medicines and medical devices meet applicable standards of safety, quality and effectiveness.

  • Ensuring that the supply chain for medicines and medical devices is safe and secure.

  • Helping to educate the public and healthcare professionals about the risks and benefits of medicines and medical devices.

  • Influencing UK, EU and international regulatory frameworks so that they are risk-proportionate and effective at protecting public health.



Online resources

The European Commission

W http://ec.europa.eu/health/files/eudralex/vol-2/a/vol2a_chap1_2013-06_en.pdf

Description. The European Commission's Notice to Applicants, Volume 2A Procedures for marketing authorisation Chapter 1 Marketing Authorisation, dated June 2013.

UK legislation

W www.legislation.gov.uk/uksi/2012/1916/memorandum/contents

Description. The official explanatory memorandum to the Human Medicines Regulations 2012 (HMRs).

UK MHRA official guidance on manufacturer or wholesaler of medicines licences

W www.gov.uk/apply-for-manufacturer-or-wholesaler-of-medicines-licences

Description. Official guidance regarding applying for manufacturer or wholesaler of medicines licences. The guidance was first published on 18 December 2014.

UK MHRA official guidance note for applicants and holders of a manufacturer's licence

W www.gov.uk/government/uploads/system/uploads/attachment_data/file/405883/Medicines_-_notes_for_applicants_and_holders_of_a_manufacturer_licence.pdf

Description. Official guidance note for applicants and holders of a manufacturer's licence. The guidance was last updated in 2014.

UK MHRA official guidance concerning importing human medicines into the UK

W www.gov.uk/import-a-human-medicine

Description. Official guidance concerning importing human medicines into the UK. The guidance was first published on 9 August 2005.

UK MHRA official guidance concerning advertising medicines in the UK

W www.gov.uk/advertise-your-medicines

Description. Official guidance concerning advertising medicines in the UK. The guidance was first published on 18 December 2014.

UK MHRA Blue Guide on the advertising and promotion of medicines in the UK

W www.gov.uk/government/publications/blue-guide-advertising-and-promoting-medicines

Description. Blue Guide on the advertising and promotion of medicines in the UK. The Blue Guide was last updated in September 2014.

UK MHRA official guidance concerning parallel imports of medicines

W www.gov.uk/medicines-apply-for-a-parallel-import-licence

Description. Official guidance concerning parallel imports of medicines. The guidance was last updated on 10 April 2015.

UK MHRA official guidance concerning the definition of a medicinal product

W www.gov.uk/government/uploads/system/uploads/attachment_data/file/398998/A_guide_to_what_is_a_medicinal_product.pdf

Description. Official guidance concerning what is a medicinal product. The guidance was last updated in November 2012.

UK MHRA official guidance concerning the supply of unlicensed medicinal products

W www.gov.uk/government/uploads/system/uploads/attachment_data/file/373505/The_supply_of_unlicensed_medicinal_products__specials_.pdf

Description. Official guidance concerning the supply of unlicensed medicinal products ("specials"). The guidance was published in 2014.

UK MHRA official guidance concerning biosimilar products

W www.gov.uk/drug-safety-update/biosimilar-products

Description. MHRA official guidance concerning biosimilar products. The guidance was first published on 1 February 2008.

Code of Non-broadcast Advertising, Sales Promotion and Direct Marketing (CAP Code)

W www.cap.org.uk/Advertising-Codes/Non-Broadcast.aspx

Description. The latest edition of the CAP Code that has been in force since 1 September 2010.

Code of Broadcast Advertising (BCAP Code)

W www.cap.org.uk/Advertising-Codes/Broadcast.aspx

Description. The latest edition of the BCAP Code that has been in force since 1 September 2010.

European Medicines Agency (EMA)

W www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/document_listing/document_listing_000318.jsp

Description. Official guidance from the EMA concerning biosimilar medicines.

European Commission

W http://ec.europa.eu/growth/sectors/medical-devices/regulatory-framework/revision/index_en.htm

Description. The European Commission update on revisions to medical devices legislation.



Contributor profiles

Andrew Skipper

Hogan Lovells International LLP

T +44 (0) 207 2923
E andrew.skipper@hoganlovells.com
W www.hoganlovells.com

Professional qualifications. England and Wales, Solicitor

Areas of practice. Regulatory and commercial law.

Jane Summerfield

Hogan Lovells International LLP

T +44 (0) 207 5732
E jane.summerfield@hoganlovells.com
W www.hoganlovells.com

Professional qualifications. England and Wales, Solicitor

Areas of practice. Regulatory and commercial law.

Amy Merrick

Hogan Lovells International LLP

T +44 (0) 207 5415
E amy.merrick@hoganlovells.com
W www.hoganlovells.com

Professional qualifications. England and Wales, Solicitor

Areas of practice. Regulatory and commercial law.


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