The British Pharmacopoeia — happy 150th birthday to “the chemist’s bible”
Tony Cartwright reviews the involvement of pharmacy and pharmacists with the British Pharmacopoeia, which celebrates its sesquicentenary on 26 January 2014
Retired pharmacists will have become familiar with the British Pharmacopoeia (BP) from their student days when they had to purchase a copy of the big red book to find out how to make up some of the mixtures and other preparations which were then prescribed.
Purchasers of the BP 2014 will now receive the six-volume printed edition, including the BP (Veterinary), a CD-ROM and a licence to the online version. Corporate purchasers can obtain a network licence for multiple users. The book now contains almost 3,500 monographs, including those in the European Pharmacopoeia. But where did it all start?
In 1618 the Royal College of Physicians published the first edition of the London Pharmacopoeia. The Worshipful Society of Apothecaries of London had been incorporated by royal charter in December 1617. A proclamation was issued by James I on 26 April 1618 informing the Apothecaries what was to be expected of them:“Apothecaries within our Realme of England or the dominions thereof … do not compound or make any medicine, or medicinal receipt or prescription — by any other books or Dispensatories whatsoever but after the onely manner that hereby is, or shall be directed, prescribed or set downe by the said booke.”
The first edition of May 1618 was found to be full of errors and a revised definitive edition was published on 7 December 1618. The text was in Latin because it was meant only to be used by learned physicians and apothecaries, and not for the information of the common man. The December edition described 1,190 ingredients, many derived from plants, but some from animal parts and minerals such as amethyst, beryl, opal and sapphire. The preparations included waters, wines, syrups, powders, troches (lozenges), oils, ointments and plasters.
Further editions were published over the years. The 1836 edition included some of the recently discovered alkaloids such as aconitine, morphine, quinine and strychnine. The 10th and final edition was published in 1851 and included chloroform and cod-liver oil.
In August 1745 the College of Physicians of Ireland agreed to use the London Pharmacopoeia for their prescriptions and they continued to use it until 1806, when the first Dublin Pharmacopoeia was published. The final Dublin Pharmacopoeia came out in 1850 and was reprinted in 1856. The first edition of the Edinburgh Pharmacopoeia was published by the Royal College of Physicians of Edinburgh in 1699. This was frequently reviewed and revised. A further 11 editions were published, the last being the 1839 edition, which was published in English for the first time.
The Medical Act 1858 established a General Medical Council (GMC) of Medical Education and Registration of the United Kingdom. It established a register of medical practitioners. Section LIV of the Act required the GMC to publish “a Book containing a list of Medicines and Compounds, the Manner of preparing them, together with the true Weights and Measures by which they are to be prepared and mixed … ”. The purpose of the new book was to supersede the three national pharmacopoeias, so it was essential to set up national committees to help with the work.
Three branch committees were set up in London, Edinburgh and Dublin, and work started in December 1858. A total of 407 meetings were held, together with two conferences of delegates in London and Edinburgh. The GMC formally announced the publication of the first edition of the BP on 25 January 1864 in the London Gazette. It consisted of two parts and two appendices. The first part comprised the Materia Medica, the second the preparations and compounds. Each of the materia medica was given a Latin name and an English name.
Unsurprisingly, in view of the different national traditions of prescribing developed over many decades the book was not popular and was heavily criticised. Physicians could not find many preparations with which they were familiar or, if they could find them, they had a different composition.
The GMC then selected a Pharmacopoeia Committee from among its members to start work on a new edition. Two editors were appointed: Robert Warrington, FRS, who was the chemical operator at the Society of Apothecaries, and Theophilus Redwood of the Pharmaceutical Society.
The new revised edition published in 1867 followed a plan drawn up by Redwood. It incorporated many of the published researches of Redwood and John Attfield who, at this time, was the professor of practical chemistry at the School of Pharmacy at the Pharmaceutical Society. There was an emphasis on quality with tests to identify and test the purity of commercial materials. It was well received and The Pharmaceutical Journal stated that it was “a decided success”.
The 1874 Addendum to the BP 1867 was prepared with Attfield as the editor. The third edition was published in 1885 with Redwood, Attfield and Robert Bentley as joint editors. Bentley was a pharmacist who subsequently studied medicine and became professor of botany at King’s College London. Glyceryl trinitrate tablets were included in this edition.
|Photograph of Robert Bentley, Theophilus Redwood and John Attfield, 1878, who were joint editors of the third edition of the British Pharmacopoeia (Royal Pharmaceutical Society Museum)|
Another addendum was published in 1890, with Attfield again acting as its editor. Each edition necessitated extensive consultation with the medical and pharmaceutical authorities in 29 colonial governments so that the lists of additions and omissions reflected the needs of the British Empire.
The fourth edition was published in 1898. This was prepared for the GMC Pharmacopoeia Committee with Nestor Tirard as its secretary. Tirard was a consulting physician at King’s College. A Committee of Reference in Pharmacy gave pharmaceutical advice to the Pharmacopoeia Committee.
This committee was chaired by Walter Hills and included William Martindale among its members. In 1893 the Secretary of State for India asked the GMC to investigate how the pharmacopoeia could be better fitted to suit the needs of India and the Colonies. An Indian and Colonial Addendum was published in 1900, again with Attfield as its editor.
From 1900 onwards regular conferences had been held between members of the GMC Pharmacopoeia Committee and the Pharmaceutical Societies of Great Britain, Ireland and Northern Ireland. These recommended the programme of practical investigations needed for the next edition. This work was done by Henry Greenish at the Pharmaceutical Society’s laboratories. In November 1911 Tirard and Greenish were appointed as editors of the next edition, which was published in 1914. Drugs included for the first time included aspirin, diamorphine hydrochloride and phenolphthalein. Doses were given in both the imperial and metric systems.
In November 1903 the Council of the Pharmaceutical Society decided to produce its own reference book. The first edition of the British Pharmaceutical Codex was published in 1907. It claimed to cover all drugs and medicines in common use throughout the British Empire, France, Germany and the US.
A growing dissatisfaction
Although the GMC Pharmacopoeia Committee consulted on the choice of drugs and preparations for new editions of the BP and then chose the list of those to be included or omitted, the bulk of the work for a new edition of the BP was to draw up the quality standards. Most of this work was done by the Committee of Reference in Pharmacy set up by the Pharmaceutical Society. But pharmacists had no seat on the GMC Pharmacopoeia Committee and felt an increasing dissatisfaction with their subservient role.
In 1914 the Pharmaceutical Society unofficially advised Tirard that it would not continue to work with the GMC under the current arrangements. However, during the 1914–18 war, some of the official preparations were reformulated by the Pharmaceutical Society’s laboratory to overcome wartime shortages of materials, such as sugar and glycerol (used to manufacture nitroglycerin for munitions).
In 1925 the GMC Pharmacopoeia Committee began work on a new post-war edition and sought the help of the medical and pharmaceutical authorities, including the Pharmaceutical Society. In November 1925 the Council of the Pharmaceutical Society resolved that, if it were asked to co-operate but without an invitation to appoint nominees to the Pharmacopoeia Committee, this would be refused.
The GMC then suggested setting up additional committees reporting to the Pharmacopoeia Committee, one of which could include three Pharmaceutical Society nominees. However, it stressed that the GMC would have the final say in respect of the advice and suggestions. This was unacceptable and Sir William Glyn-Jones, the Secretary of the Pharmaceutical Society, wrote to the Lord President of the Privy Council expressing the “profound dissatisfaction” of the council and asking for the appointment of a committee of inquiry.
The GMC’s Pharmacopoeia Committee held a conference on 23 February 1926 to which delegates from the various medical and pharmaceutical bodies were invited. Many were highly critical of the current content of the book and its method of production. A Cabinet subcommittee was set up to consider the reform of the pharmacopoeia chaired by Hugh Macmillan KC, a former Lord Advocate and a Privy Councillor. The subcommittee received both written and oral evidence during 1925 and 1926. Much of it was a damning indictment of the existing arrangements.
Professor Greenish had reviewed the work of Pharmacopoeia Commissions in 21 countries, all of which included both medical and pharmaceutical experts. The Macmillan subcommittee reported in March 1928 recommending the appointment of a Selection Committee composed of members nominated by the GMC, the Pharmaceutical Societies and the Medical Research Council. They would appoint a new Pharmacopoeia Commission. A permanent secretary should be appointed with an office and staff.
A new commission
The new Pharmacopoeia Commission took up office in December 1928 chaired by Arthur Beddard, a retired consulting physician. Charles Hampshire was appointed in February 1929 as the first secretary to the commission. At the time of his appointment he was the chief pharmacist at University College Hospital. He was qualified in pharmacy, had a degree in chemistry and, while working at UCH, he had also qualified in medicine.
The new commission met fortnightly and was assisted by six subcommittees. The Pharmaceutical Society had set up a laboratory for work on the Codex and use of the facilities was provided to the commission. The new edition became official in October 1932. It attracted interest from both the professional press and newspapers. The Bath Chronicle and Herald headlined “New issue of chemists’ bible”. The article mentioned that 23,000 chemists would have to spend the weekend in a process of “instantaneous assimilation” of its contents. Seven Addenda to the BP 1932 were published.
During the 1939–45 war the British chemical manufacturers were asked to produce drugs that had been formerly been imported, and the BP Commission produced and published standards for them and provided approved names. In 1941 the commission’s offices and laboratory at the GMC premises in Hallam Street had been damaged by bombs and they moved to temporary accommodation at the Pharmaceutical Society and then to University College. A new edition of the BP was prepared by November 1946, although it was not published until 1948 due to paper shortages. Dr Hampshire retired in 1950 and he was replaced by Thomas Denston, a pharmacist who had formerly edited the Codex.
New editions of the BP were published in 1953, 1958 and 1963. The BP 1963 contained almost 1,000 monographs, 200 of which appeared for the first time. In 1963 the BP Commission commented on a proposal to create a common pharmacopoeia to serve the needs of a number of European countries. This was to lead to the founding of the European Pharmacopoeia in 1964. In 1963 Cecil Johnson joined the staff of the pharmacopoeia from the Pharmaceutical Society’s laboratory, where he had been working on monographs for the Codex and British Veterinary Codex. In 1967, when Denston retired, Johnson was appointed as scientific director to serve alongside George Kitteringham as secretary to the commission.
In the wake of the thalidomide disaster the Government introduced legislation in 1968 which would provide that future editions of the pharmacopoeia would be prepared under the direction of a new body, the Medicines Commission. The Medicines Act received Royal Assent in October 1968. Copyright in the BP was transferred from the GMC to the Crown. The staff of the commission and its laboratory became civil servants in the medicines division of the Department of Health. A new edition was published in 1968.
Another new edition was published in 1973. The British Pharmacopoeia Commission responsible for this edition was chaired by Frank Hartley, dean of the School of Pharmacy of the University of London. He was the first non-medical chairman of the commission. New editions were published every five years, with Addenda in between to respond to the rapid pace of drug development and analytical advances. In 1988, after the retirement of Cyril Johnson, Alan Rogers was appointed as secretary and scientific director. He had been a member of the BP staff since 1984. He retired in 1990 and Robin Hutton, a chemist, was appointed as secretary and scientific director.
Rising demands and delays in licensing had led to the creation of the Medicines Control Agency (MCA) in 1989, one of the executive agencies of the Department of Health. Hutton was charged with the task of ensuring that the BP became self-sufficient so that the revenue from sales of the book and the reference substances was balanced with the costs of production and servicing its advisory committees.
Hutton introduced yearly editions of the BP and the first CD-ROM edition of any pharmacopoeia. His successors Gerald Lee (2001–11) and now Samantha Atkinson at the Medicines and Healthcare products Regulatory Agency have built on this success. The pharmacopoeia generated an income in 2012–13 of £2.85m, with a surplus of £188,000.
The evolution continues
Since 1928 the British Pharmacopoeia has evolved from a formulary for pharmacists to a book providing comprehensive analytical standards for manufactured drugs. It now includes monographs for medicinal substances, formulated preparations, biological and biotechnological products, radiopharmaceuticals, surgical materials, herbal medicines, homoeopathic preparations and unlicensed medicines. The BP Commission publishes the list of British Approved Names.
Members of the committees and working parties provide expert input to the work of the European Pharmacopoeia. It collaborates with the US Pharmacopeial Convention, the World Health Organization and the Chinese Pharmacopoeia. Its latest chairman, Kevin Taylor, the head of the department of pharmaceutics at the School of Pharmacy, University College London, was appointed in October 2013. It has been a world leader in medicinal standards for 150 years and will continue to build on this tradition.
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11133216
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