A Brief History of Pharmacopoeias

Everyone involved in pharmaceutical raw material and finished product testing will be familiar with the pharmacopoeias such as the British, European and United States compendia, but where did it all start?

You may be surprised by just how far back such medical compilations can be traced. There have been lists of medicinal plant remedies dating back thousands of years, including those from ancient Egypt (the Eber Papyrus), Mesopotamia, the Shennony Ben Cao Jing from China in the 3^rd century BCE, and the Greek De Materia Medica written in the 1^st century CE and referred to for over 1,500 years.

These texts existed to describe medicines derived from plants, animals, and minerals, and to explain how to prepare and use them. They were, however, often not well controlled or researched, and over time these collections began to evolve into something a little more regulated.

The earliest officially sponsored pharmacopoeia known was the Xinxiu bencao, produced during the Tang dynasty by 23 scientists, containing close to a thousand descriptions of medicines and used across China for 400 years.

In Europe, during the 14^th century, city pharmacopoeias started to emerge. These were early attempts to collect medical prescriptions and impose some consistency, so that customers of apothecaries and doctors would have more confidence that what was purchased from two different places would be comparable. Notable examples included those produced in Nuremberg, Florence, Barcelona, Paris and Lyon. The Pharmacopoea Amstelredamensis was produced under the supervision of the mayor of Amsterdam in 1636 as an attempt to improve public health after an outbreak of the Bubonic plague and control some of the less reputable apothecaries in the city.

Over time, it became clear that there were anomalies and potentially dangerous inconsistencies between these city volumes, and so an early example of harmonisation was used to create the British Pharmacopoeia in 1858, combining the Edinburgh, London and Dublin publications. Similarly, the United States Pharmacopoeia (USP) was created in 1820 to provide consistency across all states.

“In the United States, the evil of irregularity and uncertainty in the preparation of medicines has been felt with peculiar weight.” (Preface, first issue of United States Pharmacopoeia)

There are estimated to be up to 40 pharmacopoeias in publication at the moment.

The European Pharmacopoeia (Ph. Eur.) was a little different; it was created following a convention in 1964, with a focus on modern manufacturing and regulatory systems, and to facilitate the free movement of medicines within the European Union. It has mostly replaced national pharmacopoeias, so although many countries maintain their own as a complement or to include items of national interest, the European Pharmacopoeia takes legal precedence.

The World Health Organisation began work on an International Pharmacopoeia in 1947 with the lofty ideal of unifying all pharmacopoeias globally, but this proved difficult to achieve. The purpose of the volume was reconsidered in 1975 with a focus on producing something that could be used in developing countries, containing accessible methodology and covering important drug use throughout the world and medications likely to include impurities. It now concentrates on medicines of the highest public health concern, such as the treatment of malaria, tuberculosis and HIV/AIDS.

International harmonisation remains a long-term goal supported by the International Council for Harmonisation. With every new edition, the number of harmonised monographs in the Ph. Eur. and USP continues to increase, but the process is slow, and there is a long way to go before anything like international harmonisation of all medication is reached, with not only practical but also political barriers potentially slowing the process.

This lack of harmonisation can have real-world implications. Needing to have materials tested to multiple pharmacopoeias increases costs and can increase lead times, has a negative environmental impact as more reagents are required, and could potentially restrict the use of some medications in certain territories. If you need any pharmacopoeia testing or have any questions about them, Butterworth Laboratories can help. We have decades of experience and are used to interpreting the often tricky compendia requirements and have tested to some of the more unusual publications including the Russian, Indian (Ayurvedic), French and German pharmacopoeias. We regularly communicate with the various commissions to get to the bottom of sometimes conflicting requirements or problematic methods. We also specialise in verifying pharmacopoeia tests and validating methods when they prove not as robust as they should be.

Tim Goddard

Laboratory Manager – General & Inorganic