Pharmacopoeia Compliance Series A Brief History of Pharmacopoeias: A Global Perspective

J. Mark Wiggins and Joseph A. Albanese

he global and historical perspective presented herein is critical to understanding the particular challenges that must be overcome to achieve harmonization among the pharmacopoeias, as well as providing a Tdeeper appreciation of the important harmonization prog- ress achieved to date. Also, by understanding the lack of

iQoncept/stock.adobe.com harmonization, the reader will appreciate the complexity it adds to a company’s processes for compendial monitoring In this series of articles, the authors provide an understanding and compliance. about the need for pharmacopoeia compliance. The following articles can be found within this ebook and online Pharmacopoeias–A global perspective and brief history at www.PharmTech.com/compendia: According to the latest index compiled by the World Health • Why Pharmacopoeia Compliance is Necessary Organization (WHO) (1), there are as many as 40 pharma- • Why Pharmacopoeia Compliance is Difficult copoeias published around the world, with as many as 60 • A Brief History of Pharmacopoeias: A Global Perspective active pharmacopoeia commissions who carry out the work • Global Pharmacopoeia Standards: Why Harmonization of developing and maintaining these pharmacopoeias (Table is Needed I). To better understand the situation today, it is instructive • Harmonization Efforts by Pharmacopoeias and to consider the history of pharmacopoeias. A timeline is Regulatory Agencies provided in Figure 1 indicating the year when many of the Upcoming articles in this series will include the following: pharmacopoeias were created. Although the earliest work • Revision Process for Global/National Pharmacopoeias presenting medical knowledge and remedies may • Surveillance Process for Industry: Monitoring date back more than 3000 years to ancient (2), it Pharmacopoeia Revisions was De , which appeared in the 1st century • Monograph Development: Why and When to Participate CE in Greece and Rome that perhaps represents the first • Monograph Development: How to Participate; How to example of a “pharmacopoeia” (3). (The word “pharmaco- Harmonize poeia” translates from the as “drug-making”.) • A Practical Approach to Pharmacopoeia Compliance This treatise on medical matters compiled herbal remedies • A Case Study in Pharmacopoeia Compliance: Excipients known at the time, along with their methods of preparation. and Raw Materials Beginning in the 16th century, several pharmacopoeias con- • Pharmacopoeia Compliance: Putting it All Together; taining medical prescriptions were prepared for apothecar- What is on the Horizon ies and physicians in important cities of Europe, including Nuremburg (4), , Edinburgh, and Dublin (5). BP and USP–early efforts to harmonize pharmacopoeias J. Mark Wiggins is owner and compendial In the 19th century, it was recognized that there were in- consultant with Global Pharmacopoeia Solutions LLC. Joseph A. Albanese is the director of Analytical consistencies in the information contained in the various Strategy and Compliance at Janssen Research and pharmacopoeias which then existed. As a result, there was Development, LLC. an emerging focus on efforts to standardize and harmonize the content in the pharmacopoeias. An early example of the

Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 1 Pharmacopoeia Compliance Series

Table I. Pharmacopoeia commissions/published pharmacopoeias The development of the compiled from World Health Organization data (1).

USP and BP were intended to Pharmacopoeia Pharmacopoeia Pharmacopoeia Pharmacopoeia commission published commission published

harmonize drug standards. Argentina# √ Macedonia+ Austria* √ Malta* Belarus## √ √ need for pharmacopoeial harmonization was the creation Belgium* Montenegro* Bosnia and of the (BP) in 1858 to overcome the Netherlands* inconveniences and dangers resulting from the existence of Herzegovina* three different pharmacopeias in the United Kingdom and # √ Norway* Ireland, those of London, Edinburgh, and Dublin (5). Even Bulgaria* Pakistan √ Chilex √ Philippines √ earlier, in 1820, the United States Pharmacopeia (USP) was √ Poland* √ established by a group of 11 physicians who held the first Croatia* √ * √ United States Pharmacopeial Convention (USP) in the US Republic of Cyprus* √ Capitol building in Washington, because they recognized Korea the need for consistent standards for the that Czech Republic* √ Romania* √ Russian were being used in the separate states of the relatively young Denmark* √ Federation## “united” country. Information contained in the preface to Egypt √ Serbia* the first edition of the USP provides an early reference to Estonia* Slovak Republic* √ the historical purpose, value, and usefulness of the phar- Finland* Slovenia* macopoeias, which also provides interesting perspectives for * √ * √ today (6). Modern pharmacopoeias strive to achieve similar Germany* √ Sweden* value and usefulness, while shifting away from historical Greece* √ * √ “recipes” that described methods of preparation for medi- * √ Thailand √ cines, to instead focus on the attributes of drug products and Iceland* Turkey* ingredients that help ensure their identity, strength, quality, India √ Ukraine* √ and purity. The preface to the first edition of the USP con- Indonesia √ United Kingdom* √ tinues with the following remarkable comments that speak Iran √ United States √ to the need and value of harmonization to achieve consis- Ireland* Vietnam √ tency in pharmacopoeial standards (6): * √ Regional/International Japan √ Africa √ Eurasian Kazakhstan## √ √ • “In the United States the evil of irregularity and un- Economic Union## certainty in the preparation of medicines has been felt Latvia* Europe* √ with peculiar weight.” Lithuania* MERCOSUR# √ • “… (A) number of Pharmacopoeias … have been pro- World Health Luxembourg* √ duced in different parts of the Union … and of course Organization++ the character of medicinal preparations is liable to * Pharmacopoeia authorities are a party to the European vary in every state and city of the Union.” Pharmacopoeia Convention. # Participating countries in the MERCOSUR Pharmacopoeia: • “… (A) National Pharmacopoeia … should be estab- Argentina, Brazil, Paraguay, Uruguay. lished and adopted … being evidently the only mode ## Participating countries in the Eurasian Economic Union (EAEU) by which a uniform system could be introduced at Pharmacopoeia: Armenia, Belarus, Kazakhstan, Kyrgyzstan, Russian Federation. once into all parts of the American territory.” x Pharmacopoeia authority not active. The work of the convention that introduced this uniform + Former Yugoslav Republic of Macedonia. system of drug standards and led to the initial creation of ++ The World Health Organization (WHO) publishes the International the pharmacopoeia of the United States continues today, Pharmacopoeia (Ph. Int.). with the next meeting of stakeholders scheduled in May 2020, marking the 200th anniversary of the USP. However, the establishment of the USP in 1820 occurred long before of the 1906 Pure Food and Drug Act (7), nearly a century modern bio/pharmaceutical manufacturing capabilities and after the first USP was published. The USP and National regulatory systems that are in place today around the world (NF) were subsequently recognized as official to control the quality, safety, and efficacy of drug products. compendia in the 1938 Federal Food, Drug, and Cosmetic Although it was not known by its present name until 1930, Act (FD&C Act). In 1975, USP acquired the previously FDA’s modern regulatory functions began with the passage separate compendium NF and the first combined edition

2 Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 PharmTech.com Figure 1: Timeline indicating the year when many of the pharmacopoeias were created.

1898 1962 Local 1820 1858 Argentina Indonesian pharmacopoeias United States British Pharmacopoeia Pharmacopoeia 1964 are created in 2004 2020? Pharmacopeia Pharma- is created is created European 1987 some cities and Philippine EAEU is created – for copoeia Pharmacopoeia is Thailand city-states 1953 Pharma- Pharmacopoeia >20 US states is created – 1929 created – first regional Pharmacopoeia around the globe Modern pharmacopoeia with 8 is created copoeia is first publication – from 3 UK city Brazilian pharma- Chinese member states of the created from 5 Eurasian Pharma- copoeias Pharmacopoeia Council of Europe Economic Union copoeia is created states is created Until 1800 – 1871 – 1951– 1964 – 1986 – Beyond 1800 1870 1950 1963 1985 2020 2020

1844 1846 1866 1886 1951 1958 1970 2008 TBD Indian Mexican Russian Japanese International Korean Vietnam Kazakhstan MECOSUR Pharmacopoeia Pharma- Pharma- Pharma- Pharmacopoeia Pharmacopoeia Pharma- Pharmacopoeia Pharmacopoeia is initially created copoeia is copoeia copoeia is is created by is created copoeia is is created first publication – created is created created WHO created from 4 Southern Common Market (South American) 1955 1980 countries Modern Indian First Combined Pharmacopoeia United States is created Pharmacopeia- National Formulary is published

of the USP–NF, as it is known today, was released in 1980. amples bring awareness of the overall timeline for develop- The USP–NF remains unique today among pharmacopoe- ment of the pharmacopoeias and provide the larger global ias, because it is developed by a private, non-governmental context to aid in understanding the continuing efforts to standards-setting organization. Unlike most other pharma- achieve some degree of compendial harmonization. copoeias, which are affiliated with, or formally part of the Based on traditions for curing illnesses dating back to the regulatory agency in that country or region, the USP–NF is 2nd millennium BCE, the classic Shen-nung Pen-ts’ao Ching not part of, nor is it affiliated with the US FDA. Still, USP represents the oldest known pharmaceutical work in China, and FDA have a long-standing collaboration and maintain a compilation of traditional Chinese materia medica (8). official contact through a number of established channels The current Chinese Pharmacopoeia (ChP) also has an in- to help ensure the standards that are published in USP–NF teresting history for the establishment of quality standards and enforced by FDA (among their many other responsibili- for medicines, reflecting the great importance attached to ties) contribute to the quality of medicines. The historical and healthcare by the Chinese government for the context and practical considerations in the development of people of China (9). In 1949, the year the People’s Republic the USP and FDA have led to instances where the pharma- of China was founded, the Ministry of Health convened a copoeia and regulatory requirements in the US are not fully meeting of medical and pharmaceutical experts to compile aligned, making it difficult to comply with both standards. a national pharmacopoeia for China. Over the following several years, a process for developing the pharmacopoeia Historical perspective for other pharmacopoeias was established, including a secretariat and experts charged A broader consideration of today’s global community re- with carrying out the practical and technical aspects of the veals a more complex situation with compliance challenges work. The first edition of the Chinese Pharmacopoeia was that result from the lack of broad harmonization across the published in 1953, containing 531 monographs for drug various pharmacopoeias and regulatory agencies around the substances and products, including chemical medicines world. The publication of the USP in 1820 and the BP in 1858 and traditional medicines of plant and animal origin. The aimed to bring consistency to drug standards for the benefit first addendum to the 1953 edition was published in 1957. of and medical practitioners and their patients. Since then, the content in the pharmacopoeia has continued This objective has been pursued in other countries, continu- to expand. The latest (10th) edition of the Pharmacopoeia ing to modern times, with the initial development and sub- of the People’s Republic of China, referred to as the ChP, was sequent updates to their pharmacopoeias. As noted earlier, published in 2015 and consists of four volumes covering there are currently as many as 40 pharmacopoeias published traditional Chinese medicines, modern chemical medicines around the world, each with its own rich and unique history, and antibiotics, biologics, excipients, and general chapters while sharing a common goal of providing quality standards (10). ChP 2015 contains more than 5600 monographs, 10

FIGURE COURTESY OF THE AUTHORS THE OF COURTESY FIGURE for medicines to benefit patients. Additional historical ex- times the number in the first edition, including more than

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1000 new monographs since the previous edition that was throughout member states and ensured access to medicines published in 2010, and more than 300 general chapters and by European citizens. Today, this convention has 39 signa- requirements. The next edition of ChP is in development, tory parties from Europe, including the , with publication planned for 2020. in which there is mandatory compliance with the require- The history of the Indian Pharmacopoeia (IP) (11) began ments of the Ph. Eur. These member states participate and in 1833, when a committee recommended publication of vote in the Commission sessions, a pharmacopoeia, which was first completed in 1844 and where the standards published in the Ph. Eur. are adopted mainly consisted of commonly used indigenous remedies. A (14). Currently, there are also 30 observers from all over the subsequent publication in 1868 included not only the indig- world, including the US, China, and WHO, that are able to enous drugs used in India, but also the drugs of the British participate in the scientific work of the Commission and Pharmacopoeia. Then in 1885, the BP was made official in benefit from the European experience in this area. Observ- India. After independence from Britain, the Indian Pharma- ers also gain access to the work on the quality control of copoeia Commission was established in 1948, with its main medicines and the methods of analysis in the Ph. Eur., which function being the publication of IP as the national pharma- could further support compendial harmonization through copoeia. The first edition of the modern IP was published adoption or adaptation of the Ph. Eur. standards. in 1955, and the current 8th edition was published in 2018. The Ph. Eur. marks the creation of a single, unified re- Elsewhere, the first edition of the Russian Pharmacopoeia gional pharmacopoeia—it may be argued even an interna- (now the State Pharmacopoeia of the Russian Federation or tional pharmacopoeia—providing legally binding standards SP RF) dates back to 1866 (12); it is now in its 14th edition, for the quality of medicines and their ingredients in Europe which was published (in Russian and on-line only) by the for the signatories to the convention, where previously there Russian Ministry of Health in December 2018, with imple- had been separate pharmacopoeias in each member country. mentation required by January 2022. The Japanese Pharma- This represents an important advance in the historical evo- copoeia (JP) was first published in 1886 (13) and is now in its lution of pharmacopoeias to move toward global standards. 17th edition including two supplements, with the 18th edi- With this achievement, why are there still pharmacopoeias tion planned for publication in 2021. The pharmacopoeias in some individual countries in Europe? Maintaining a na- in Mexico and Argentina were first published in 1846 and tional pharmacopoeia in these countries provides text that 1898, respectively (1). The first edition of the Brazilian Phar- is either of interest to one member state only, or out of scope macopoeia was published in 1929 (1) and is currently in its of the Ph. Eur. (e.g., national formularies) (15). Three main 5th edition including two supplements, with an updated 6th approaches were taken in Europe following the creation of edition nearing completion. The Korean Pharmacopoeia was the Ph. Eur., with the decision being country specific: first published in 1958 (1); the Indonesian Pharmacopoeia in • Discontinuation of the national pharmacopoeia (e.g., 1962 (12). Other recent examples include the pharmacopoe- Sweden, Finland, Netherlands); Ph. Eur. established as ias in Vietnam, Thailand, the Philippines, and Kazakhstan, the only pharmacopoeia, potentially translated into first published in 1970, 1987, 2004, and 2008, respectively (1). the national language Each pharmacopoeia was initially established to stan- • Inclusion of the Ph. Eur. content in the national phar- dardize medicines and serve the needs of patients within macopoeia (e.g., United Kingdom [BP], Spain) their respective country. Today, a global view is necessary • Publication of the national pharmacopoeia in addi- in order to meet the needs of global patients. Within this tion to the Ph. Eur. (e.g., France, Germany, Switzer- perspective, there is a special place held by the European land, Austria). Pharmacopoeia (Ph. Eur.) and the International Pharmaco- Regardless of the approach taken, the standards con- poeia (Ph. Int.), each of which deserves further consideration. tained in the Ph. Eur. remain mandatory in these countries, even as their national pharmacopoeia serves to complement Ph. Eur.–Creation of a modern, the content of the Ph. Eur. by including standards for drug harmonized pharmacopoeia products and ingredients that are applicable in that indi- In their historical context, the development of the USP vidual country. and BP were intended to harmonize drug standards. But An article written by the Director of the European Direc- unlike the USP, BP, and many other pharmacopoeias, the torate for the Quality of Medicines and HealthCare (EDQM) more recent creation of the Ph. Eur. occurred within the provides perspective on the continuing role of the pharma- context of modern manufacturing and regulatory systems copoeia in the 21st century (3). The article describes how in Europe and around the world, providing a recent and pharmacopoeias continue to modernize in changing times successful example of harmonization. In 1964, the Conven- to support the availability of affordable medicines without tion on the Elaboration of a European Pharmacopoeia, set compromising their quality, safety, and efficacy. The 9th forth by eight member states of the Council of Europe, es- edition of the Ph. Eur., which became official in January tablished harmonized standards for medicines in Europe (5). 2017, has continued to add new and revised general chap- The convention facilitated the free movement of medicines ters and monographs, including the publication of the first

4 Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 PharmTech.com monograph for a finished product containing a chemically and from other institutions, including national drug quality defined active substance. The Ph. Eur. has moved to allow control laboratories, WHO collaborating centers, and other the use of reverse osmosis for the production of water for standards-setting organizations (16). The eighth edition of injections (WFI) and has increased focus on impurities, Ph. Int. was published in 2018 and constitutes a collection of quality by design (QbD), process analytical technology recommended procedures for analysis and specifications for (PAT), and biotherapeutic products, including monoclonal the determination of pharmaceutical substances and dosage antibodies (mAbs). EDQM, which publishes the Ph. Eur., forms. These are intended to serve as source material for has also recognized that a high percentage of APIs come reference or adaptation by any WHO Member State (194 from outside Europe, Japan, and the US, leading to even countries) wishing to establish pharmaceutical require- further need to strengthen the collaboration among phar- ments (17). From a compliance perspective, it is important macopoeias. To mark the publication of the 10th edition of to understand that the Ph. Int. only has legal status whenever the Ph. Eur., which is official in January 2020, EDQM orga- a national or regional authority expressly introduces it into nized an international conference in Strasbourg in June 2019, appropriate legislation. bringing together leading scientists and experts to exchange views and share experiences on all aspects of the quality of medicines. The conference, titled “EDQM and European The ultimate goal of the Ph. Int. Pharmacopoeia: State-of-the-Art Science for Tomorrow’s Medicines,” highlighted developments in the Ph. Eur. to help is to provide quality control ensure that modern pharmacopoeias continue to make a specifications to help enable vital contribution to the protection of public health. access to quality medicines Other regional pharmacopoeia initiatives There have been other efforts to support the harmonization of worldwide. pharmacopoeia standards between several countries in a par- ticular region, drawing on the successful experience of the Ph. Eur. The MERCOSUR pharmacopoeia is being developed to The ultimate goal of the Ph. Int. is to provide quality con- provide harmonized compendial standards for four Southern trol specifications to help enable access to quality medicines Common Market (South American) countries: Brazil, Argen- worldwide. The Ph. Int. is published by WHO with the aim tina, Paraguay, and Uruguay. The Eurasian Economic Union to achieve wide global harmonization of quality specifica- (EAEU) pharmacopoeia, currently under development, is in- tions for selected pharmaceutical products, excipients, and tended to provide a core set of requirements for the quality of dosage forms. Compared to other pharmacopoeias, priority medicinal products in the countries of the Eurasian Economic is given to medicines that are included in the WHO Model Union, which includes the Russian Federation, Armenia, Be- List of Essential Medicines and to medicines that are im- larus, Kazakhstan, and Kyrgyzstan. It will be interesting to portant for WHO health programs; the needs of developing monitor the continued development of these pharmacopoeias, countries are taken into account (17). However, this focus including how the published compendial standards are received on essential medicines and developing countries is a fairly and accepted by the health authorities in these countries and recent development and was not always the primary inten- around the world. It remains to be seen if the existing national tion of the Ph. Int. Indeed, the goal of achieving harmonized pharmacopoeias will continue to exist, or if they will be discon- pharmacopoeia standards for drug quality is deeply rooted tinued or absorbed in the new regional publication. in the history of Ph. Int., which dates back to 1874 when the need to standardize terminology and to specify dosages and Ph. Int.–Toward global pharmacopoeia standards composition of drugs led to attempts to produce an interna- With the inclusion of “international” in its title and con- tional pharmacopoeia (18). In 1937, the League of Nations sidering the numerous other pharmacopoeias also set up an expert committee in response to repeated calls in existence today, it is useful to understand the his- from pharmaceutical experts in various countries to coor- tory and specific role played by the Ph. Int. in the global dinate the work of national pharmacopoeia commissions pharmacopoeia landscape. and develop a unified pharmacopoeia. The first committee Among its many responsibilities, WHO provides impor- comprised seven experts from Belgium, Denmark, France, tant support to global healthcare through the publication of the Netherlands, Switzerland, the United Kingdom, and the the International Pharmacopoeia. The work on the Ph. Int. United States. is carried out in collaboration with members of the WHO In 1947, WHO took over the work begun under the Expert Advisory Panel on the International Pharmaco- League of Nations for the unification of pharmacopoeias. poeia and the WHO Expert Committee on Specifications The first edition of the Ph. Int. was published in two vol- for Pharmaceutical Preparations. Also involved in this work umes (1951 and 1955) and a supplement (1959) in English, are specialists from regulatory authorities, from industry French, and Spanish, and also translated into German and

Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 5 Pharmacopoeia Compliance Series

Japanese. The Ph. Int. was originally published with the aim Acknowledgment of creating a worldwide, unified pharmacopoeia and relied The authors gratefully acknowledge the contribution of on collaboration with national pharmacopoeia commissions Susan J. Schniepp for her technical review and helpful sug- for its preparation. However. it was recommended that Ph. gestions during the preparation of this series of articles. Int. was not intended to be a legal pharmacopoeia in any country unless adopted by the pharmacopoeial authority of that country. In 1975, the purpose of the Ph. Int. was References reconsidered. It was decided that the publication should 1. WHO, “Index of World Pharmacopoeias and Pharmacopoeial Au- focus more on the needs of developing countries, apply- thorities,” World Health Organization, Working Document QAS/11.453/Rev.10, January 2018, www.who.int/medicines/publica- ing simple, classical chemical techniques for the testing of tions/pharmacopoeia/index-of-pharmacopoeias_17012018. medicines. Priority would be given to drugs that were widely pdf?ua=1 used throughout the world, with emphasis on the therapeu- 2. New York Academy of Medicine, “Academy Papyrus to be Exhib- tic value of these drugs. High priority would be accorded to ited at the Metropolitan Museum of Art,” Press Release, July 2005, drugs important to WHO health programs, and to those https://web.archive.org/web/20101127161922/http://nyam.org/ news//2493.html, Accessed September 9, 2019. likely to contain impurities arising from degradation or due 3. S. Keitel, PDA Letter, April 2019, https://www.pda.org/pda-letter- to difficulties in their manufacture. Since 1979, monographs portal/home/full-article/the-pharmacopeia-in-the-21st-century in Ph. Int. have provided specifications for the identifica- 4. A. Arber, , Their Origin and Evolution: A Chapter in the tion, purity and content for drugs in the WHO Model List History of , 1470–1670, (Cambridge University Press, p. 66, of Essential Medicines. 1912). 5. S. Keitel, Pharmaceutical Technology 34 (4), pp. 120-121 (April 2010). As with all pharmacopoeias, the activities related to Ph. 6. USP, The Pharmacopoeia of the United States of America, Copyright Int. provide an important element in the overall quality as- United States Pharmacopeial Convention, Inc., Facsimile of First sessment of bio/pharmaceuticals, thereby contributing to Edition (1820), Published by the American Institute of the History the safety and efficacy of medicines. Currently, the focus of Pharmacy, Madison, Wisconsin (2005). for Ph. Int. is on essential medicines, and more recently on 7. FDA, “The History of FDA’s Fight for Consumer Protection and Public Health,” FDA.gov, www.fda.gov/about-fda/history-fdas- priority medicines of major public health importance, for fight-consumer-protection-and-public-health, Accessed July 11, instance, medicines to treat , tuberculosis, and HIV/ 2019. AIDS, as well as medicines for children. However, from the 8. P. U. Unschuld, Medicine in China: A History of Pharmaceutics earliest times, dating back to 1874, the objective had actually (University of California Press, pp. 14-16, 1986). been to create a unified pharmacopoeia that could be used 9. Chinese Pharmacopoeia Commission, “History of the Pharmaco- poeia of the People’s Republic of China,” ChP, Vol. 1, pp. XIII - around the world—truly an international pharmacopoeia. XXIII (China Medical Science Press, 2015). 10. Chinese Pharmacopoeia Commission, “Preface,” ChP, Vol. 1, pp. IX Conclusion - XII (China Medical Science Press, 2015). The history of the pharmacopoeias around the world 11. Indian Pharmacopoeia Commission, “About IP–History of IP,” ipc. reveals a common purpose to support the health of the gov.in, https://ipc.gov.in/mandates/indian-pharmacopoeia/about-ip. html, Accessed July 11, 2019. population through consistent standards for medicines. 12. WHO, “International Meeting of World Pharmacopoeias”, WHO. Early examples, like the creation of the USP and BP at a int, www.who.int/medicines/areas/quality_safety/quality_assur- national level, as well as later examples, such as the Ph. ance/resources/qas_worldpharmmeeting/en/, Accessed June 26, Eur. on a regional level, also show an emphasis on try- 2019. ing to harmonize the quality standards contained in the 13. PMDA, “JP History and Legal Status”, Japanese Pharmacopoeia– About JP, pmda.go.jp, www.pmda.go.jp/files/000210780.pdf, Ac- pharmacopoeias. The history of the Ph. Int. demonstrates cessed June 26, 2019. that the vision of creating a unified, international phar- 14. EDQM, “Membership & Observership,” EDQM.eu, https://www. macopoeia is not new; the goal of such a pharmacopoeia, edqm.eu/en/membership-observership, Accessed July 18, 2019. which could support public health at a global level goes 15. C. Vielle, “The European Pharmacopoeia–Part 1,” Presentation at back nearly 150 years. the Workshop The Chinese and European Pharmacopoeias–The New Editions, Strasbourg, France (October 17, 2016), https://www. The next articles in this series will use the historical edqm.eu/sites/default/files/1710_1420_cv_presentation_chp_meet- context presented in Part 3 to further explore the need ing.pdf for harmonization of compendial standards, with discus- 16. WHO, The International Pharmacopoeia (Ph. Int.), WHO.it, www. sion about some of the approaches that are underway to who.int/medicines/publications/pharmacopoeia/en/, Accessed June reach this important goal. Later articles will build on this 10, 2019. 17. WHO, The International Pharmacopoeia, 8th Edition, Library information to propose a practical basis for classifying Homepage (WHO Department of Essential Medicines and Health pharmacopoeias as “global” or “national”, which enables Products, 2018), https://apps.who.int/phint/en/p/about/ a thorough consideration of the variety of approaches that 18. WHO, The International Pharmacopoeia, 8th Edition, Background may be taken by bio/pharmaceutical companies to meet to Previous Editions (WHO Department of Essential Medicines health authority expectations around the world in regard and Health Products, 2018), https://apps.who.int/phint/en/p/ docf/ PT to pharmacopoeia compliance.

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