Detailed Consideration of Global and National Pharmacopoeias

Editor's Note: Read related article, Revision Process for Global/National Pharmacopoeias

Further discussion of global and national pharmacopoeias is useful in providing context for this series of articles. Differences are revealed between the pharmacopoeias designated as global, compared with those designated as national. These differences impact the surveillance and other processes used by the bio/pharmaceutical industry to ensure compliance with pharmacopoeia requirements. The definition for a national pharmacopoeia is straightforward and the understanding is facilitated by the historical context provided earlier in this series. The national pharmacopoeias were developed to support the health of the population in that country through consistent standards for medicines. The national pharmacopoeias in Japan, China, India, Brazil, Russia, and Korea are among those published around the world that must be considered for compliance in these specific countries.

The definition for a global pharmacopoeia may not be as readily apparent and warrants further explanation. There are no specific literature or compendial references for the designation of a global pharmacopoeia. Rather, the definition is proposed by the authors, based on many years of practical experience dealing with the challenges of surveillance and compliance with pharmacopoeial requirements. Simply put, the designation as a global pharmacopoeia is based on the acceptance of the pharmacopoeia by regulators at a global level. In particular, the compendial standards published in the European Pharmacopoeia (Ph. Eur.), British Pharmacopoeia (BP), and United States Pharmacopeia–National Formulary (USP–NF) are accepted by regulators in many countries around the world to help support global access to medicines. Confirmation is provided in Table I, which shows regulatory acceptance of Ph. Eur., BP, and USP for more than 70 specific countries, based upon a regulatory intelligence database query.

European Pharmacopoeia

British Pharmacopoeia

United States Pharmacopeia

European Union*

Austria*

Belgium*

Bosnia and Herzegovina*

Bulgaria*

Croatia*

Cyprus*

Czech Republic*

Denmark*

Estonia*

Finland*

France*

Germany*

Greece*

Hungary*

Iceland*

Ireland*

Italy*

Latvia*

Lithuania*

Luxembourg*

Macedonia*

Malta*

Montenegro*

Netherlands*

Norway*

Poland*

Portugal*

Republic of Moldova*

Romania*

Serbia*

Slovak Republic*

Slovenia*

Spain*

Sweden*

Switzerland*

Turkey*

Ukraine*

United Kingdom*

Algeria

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Costa Rica

Egypt

Guatemala

Hong Kong

India

Indonesia

Iraq

Israel

Jordan

Kenya

Lebanon

Malaysia

Morocco

New Zealand

Nigeria

Panama

Peru

Philippines

Republic of Korea

Saudi Arabia

Singapore

South Africa

Tunisia

United Arab Emirates

Vietnam

Algeria

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Costa Rica

Egypt

Guatemala

Hong Kong

India

Indonesia

Iraq

Israel

Jordan

Kenya

Lebanon

Malaysia

Morocco

New Zealand

Nigeria

Panama

Peru

Philippines

Republic of Korea

Saudi Arabia

Singapore

South Africa

Thailand

Tunisia

United Arab Emirates

United Kingdom

Venezuela

Algeria

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Costa Rica

Egypt

Guatemala

Hong Kong

India

Indonesia

Iraq

Israel

Jordan

Kenya

Lebanon

Malaysia

Morocco

New Zealand

Nigeria

Panama

Peru

Philippines

Republic of Korea

Saudi Arabia

Singapore

South Africa

Tunisia

United Arab Emirates

United States

Venezuela

Vietnam

* Signatory to the European Pharmacopoeia Convention.

It is straightforward to suggest that Ph. Eur. should be considered a global pharmacopoeia, recalling that it was established to provide harmonized standards that help ensure access to medicines for citizens throughout the countries of Europe-truly an international pharmacopoeia. Compliance with Ph. Eur. requirements is mandatory in those European countries-currently 38-which are signatories to the Convention on the Elaboration of a European Pharmacopoeia. Looking at the broader global picture, it has been recently noted that Ph. Eur. is used in over 100 countries worldwide (1).

It is, perhaps, more difficult to argue that BP should be considered a global pharmacopoeia. As one of the original signatories to the Convention, compliance with Ph. Eur. requirements is mandatory in the United Kingdom (UK).

This will not change in any Brexit outcome, since the Convention was established within the Council of Europe, rather than the European Union. In publishing the BP, there is an obligation to include the entire content of the Ph. Eur., including monographs and general chapters, to ensure alignment with Ph. Eur. requirements. The BP, however, also includes requirements in addition to those in Ph. Eur.; most notably, BP contains many monographs for specific drug products containing small-molecule active ingredients. BP requirements, including drug product monographs, are accepted by regulators around the world, providing quality standards that are applicable in the UK, and also with wide international reach. These standards form an inherent part of established medicines legislation in Commonwealth countries and are used in more than 100 countries globally (2).

Similarly, USP standards are legally recognized in the United States and elsewhere and are used in more than 140 countries around the world (3). Clearly, USP requirements are accepted by regulatory agencies well beyond the geographical boundaries of the US. This near-global acceptance by regulators supports the designation of USP and BP, along with Ph. Eur., as “global” pharmacopoeias. In practical terms for global drug product registrations, the chemistry, manufacturing, and controls (CMC)/regulatory group within a company would typically reference compliance with standards in USP and/or Ph. Eur. for excipients, drug substances, and general chapters, while also referencing compliance with BP and/or USP monographs for drug products.

In considering which pharmacopoeias should be designated as global, it is relevant to mention the International Pharmacopoeia (Ph. Int.) published by the World Health Organization. As noted earlier in this series of articles, despite the inclusion of “international” in its title, the Ph. Int. was not intended to be a legal pharmacopoeia in any country unless adopted by the pharmacopoeial authority of that country. With the understanding that compliance with Ph. Int. is not widely required by regulatory agencies around the world, Ph. Int. would not be considered a global pharmacopoeia by the authors’ definitions, even though its original intention was to serve as an international standard to support the global availability of medicines.

It is recognized that other pharmacopoeias-those designated as “national”-may be accepted beyond their own geographical boundaries as well. For example, the Japanese Pharmacopoeia (JP) is also accepted by regulators in countries outside Japan. This is due, in part, to the long-standing participation of JP representatives in the harmonization work of the Pharmacopoeial Discussion Group. In some ways, JP fits squarely between the “national” and “global” pharmacopoeia designations, since many of their processes are more closely aligned with those of the global pharmacopoeias. The JP also has historical importance for the pharmaceutical markets in Japan and other Asian countries; their International Strategic Plan from 2015 includes the vision of maximizing the common health benefits to other countries and regions by positioning JP as one of the reference pharmacopoeias in Asian countries (4). However, countries that accept JP, other than Japan, would also accept Ph. Eur., BP, or USP, and it is one of these global pharmacopoeias that would usually be filed in product registrations in these countries. At a practical level, JP might only be referenced by a company in their drug product registrations for Japan. Similarly, compliance with the Chinese Pharmacopoeia (ChP) might only be included in the registration for China, even though ChP may also be accepted in other countries.

The designation of Ph. Eur., BP, and USP as global pharmacopoeias is a practical consideration, which can help address some of the challenges that a company faces in complying with the various pharmacopoeias, while aligning and simplifying the information listed in drug product registrations around the world. Still, the value of national pharmacopoeias should not be underestimated because they are critical to supporting access and ensuring quality of medicines in their respective countries.

References

1. S. Keitel, “The Ph. Eur.: A Successful Example of How a Pharmacopoeia Supports and Fosters Implementation of Regulatory Texts,” Presentation at 2nd PDA Conference on International Developments in the Pharmacopoeial Landscape, Geneva, Switzerland (May 16-17, 2019).
2. BP, “The British Pharmacopoeia,” pharmacopoeia.com.
3. USP, “Legal Recognition of USP Standards,” USP.org.
4. T. Ando, “Working Principles of Japanese Pharmacopoeia,” Presentation at 2nd PDA Conference on International Developments in the Pharmacopoeial Landscape, Geneva, Switzerland (May 16-17, 2019).