The British Pharmacopoeia (BP) has provided official standards for medicines since 1864 and its legal status was enshrined in the 1968 Medicines Act, superseded by the Human Medicines Regulations 2012. Now within the remit of the Medicines and Healthcare products Regulatory Agency (MHRA), the BP is used in more than 100 countries. The British Pharmacopoeia Commission provides expert advice to the European Pharmacopoeia (EP) on behalf of the UK and supports the work of the International Pharmacopoeia (IP) through collaboration with the World Health Organization (WHO).
Is there mutual recognition of pharmacopoeias around the world?
There is no direct mutual recognition between national pharmacopoeias, but there is supranational adoption of compendia. For example, the EP is recognised across member states of the Council of Europe, and the UK was one of the initial signatories to the convention on the elaboration of an EP.
The BP contains thousands of monographs and one of our areas of expertise is in finished products, while the EP predominantly focuses on starting materials and active pharmaceutical ingredients. We are a strong contributor to the EP, providing experts and supporting laboratory work, and the content of the EP is reproduced in the BP. This enables the BP to act as a single reference source for pharmacopoeia compliance in the UK.
Under the banner of the WHO and the IP, the Good Pharmacopeial Practices initiative is encouraging positive interactions between different pharmacopeial organisations. Run by the Essential Medicines Programme of the WHO, its primary objective is to harmonise approaches and policies in establishing pharmacopoeial standards, which will support regulatory authorities in controlling the quality of pharmaceutical ingredients and their finished products.
We’ve also undertaken informal harmonisation of product monographs in the British and US pharmacopeias, but there is value in the work of all the pharmacopeias worldwide.
Which pharmacopoeia do most pharmaceutical companies use — is the IP one of the most used?
Use of pharmacopeias is predominantly driven by regulatory or legislative requirements. In the UK, for example, compliance with the BP and the EP is mandated by the Human Medicines Regulations while, in the United States, compliance with the US Pharmacopeia is mandated by the Federal Food Drug and Cosmetic Act. Some countries may choose to recognise other national or supranational pharmacopeias. For example, in Australia, the BP, EP and US pharmacopeias are all recognised as default standards.
The IP is designed for diverse global users, including those who may not have the resources to develop their own pharmacopeia. It focuses on the WHO Model List of Essential Medicines and on priority medicines for public health, such as antimalarials and drugs for tuberculosis and HIV/AIDS. It includes analytical technologies, such as thin layer chromatography, which do not require the level of infrastructure and resources of technologies included in the BP and the US Pharmacopeia.
How has the publication of pharmacopoeias evolved to meet the changing demands of drug manufacturers?
Over time, the BP has changed significantly. We introduced a CD-ROM in the early 1990s and established our website in 1998. The website was redeveloped and launched in August 2015 and integrates our “gov.uk” and “co.uk” sites, providing a wealth of additional information and much improved functionality compared with the two previous sites. It is also an important platform for engagement with our stakeholders, including regulatory agencies that use the BP outside the UK, pharmaceutical companies and academia.
When people browse the BP online, they can now read the quality standards for a product in the monograph and then directly click and order a reference standard, rather than having to go to a separate site to order the product. So it’s a one stop shop. Other new features include a timeline that enables people to go back and look at previous versions of a monograph and review any changes, and we’ve moved to fixed publication timetables for consulting users on monograph development.
In terms of content, the quality standards have evolved to reflect the changing pharmaceutical market and the transition to new contemporary analytical technologies. Updating of monographs occurs in two ways — when stakeholders propose revisions that go through our expert advisory groups for approval, and proactive review of monographs that require deletion or revision.
Is the BP meant to ‘compete’ against pharmacopeias in terms of content or quality? For example, capreomycin, an antibiotic for multidrug resistant tuberculosis, was removed from the BP in 2003 owing to low UK use, but is still in the IP. With tuberculosis resistance a growing problem in the UK, does the IP have advantages over the BP for these types of medicines?
There is a positive collaborative spirit between the pharmaceopeias as we all recognise we are here to protect public health. When we are planning to omit a product we go through an extensive consultation process with stakeholders globally, via our website and a system of email alerts. Our expert advisory groups are continually monitoring any need to bring back a product into the BP and we regularly seek input on what is needed in the BP. We have access to information about medicines usage in the UK and we respond to requests from manufacturers or colleagues in the licensing division of the MHRA or other stakeholders for new monographs or changes to existing ones. All this feeds into a broad programme of work.
At which stage in a product’s life cycle is it usually considered for inclusion in the BP?
Most monographs are published in the BP once a medicine becomes available as a generic product but we have developed monographs on products that are still under patent protection. This depends on collaboration with manufacturers and public health needs, but the greatest benefit of producing a monograph is to establish a standard for a product before the start of generic manufacture.
What are the challenges with publishing monographs of biologics?
Biological medicines will form an important component of future global healthcare spending and the BP framework continues to evolve to accommodate the change from medicines based largely on small molecules to biologicals. We need to engage with small- and medium-sized enterprises involved in development of biologicals, as well as large multinational pharmaceutical companies, to understand their needs and demonstrate the value of the BP.
Since the MHRA merged with the National Institute for Biological Standards and Control (NIBSC) in 2013, the BP has been ideally placed to benefit from the skills, knowledge and experience of colleagues at the NIBSC for the development of quality standards for biological medicines.
Since there is less history with biologics than small molecules, we are seeking to understand what is needed in terms of standards, so I can’t yet talk about specific changes to the framework. Most of the biological medicines already in the BP are those included in the EP and, as most of the biologicals currently available are still on patent, we have time to develop appropriate criteria for quality standards. However, if there was an urgent public health need to develop a monograph for a biological product, we would do so.
Do you foresee a time when the BP will be published only online and continually updated digitally?
We are proud of the redeveloped website but some of the people who want to access the BP may not have reliable connectivity to use a web-based platform or may have other infrastructure challenges, so a hard copy version still serves an important role. I can’t say what will happen in the future, but we keep it under review with our stakeholders.
Have you had discussions with pharmaceutical companies about what they want to see from the BP?
Many of the features of the redeveloped website are the result of discussions with stakeholders, including pharmaceutical companies. In 2015, feedback from a customer insight study carried out among stakeholders in different sectors around the world was positive. There was a strong perception that the BP is authoritative, responsive and relevant. Suggestions for improvement included, for example, a proposal that draft monographs should be published on the website to a predictable, fixed timetable. We implemented that in January 2016 and we have had positive feedback from trade organisations and individual pharmaceutical companies.