US Pharmacopeia's International Activities

Don't be misled by the "US" in the name of the US Pharmacopeia (USP). Since the organization's early days, USP has been actively involved in international affairs. In fact, Congress recognized the US Pharmacopeia in the 1848 Drug Import Act specifically to establish standards to help prevent the import of adulterated drugs. This law was enacted partly in response to reports of soldiers' deaths resulting from adulterated imported drugs during the US–Mexican War (1). Similar concerns about preventing adulteration and protecting and promoting public health and standards prompted passage of the Food and Drugs Act of 1906, the Federal Food, Drug, and Cosmetic Act in 1938 (which made USP standards enforceable by FDA), the Kefauver Amendments of 1962, the Drug Price Competition and Patent Term Restoration (Hatch–Waxman) Amendments of 1984, and the FDA Modernization Act (FDAMA) of 1997. As a result of USP's long history of standards-setting, its compendia and individual monographs, the US Pharmacopeia and National Formulary (USP–NF), are officially recognized by many nations around the world, including Canada.

USP collaborates with public health officials and compendia throughout the world. Last December, Canada's Health Products and Food Branch signed a collaborative agreement with USP to take part in the testing and characterization of candidate reference standards. Reference standards are highly purified and well-characterized materials used to test a drug substance or product according to selected procedures of a monograph or General Chapter, thereby establishing the product's identity, strength, quality, and purity. USP and FDA laboratories routinely engage in the collaborative testing of reference standards (2). USP has made reference standards available since the 1960s and currently distributes them to 131 nations (3), where they play an important role in helping ensure the quality of drugs in domestic and international commerce.

USP-International

A challenge currently facing USP is how best to serve the international community of practitioners and patients while remaining committed to those in the United States. USP is exploring the advisability and feasibility of launching a new official compendium, separate from USP–NF, for articles not marketed in the United States (4). The tentatively titled USP-International (USP-I) could work synergistically with the World Health Organization's International Pharmacopoeia and could include basic and screening procedures to assist customs officials and practitioners in the field. One important effect would be to help reduce the circulation of counterfeit and substandard drugs. USP-I also could help international regulatory bodies because validated analytical procedures and official USP reference standards would be available for drugs included in USP-I. The reference standards also would facilitate international commerce of quality drug products (e.g., by building confidence in their acceptance testing) and help international sponsors who wish to submit an application to FDA for US marketing. Conversely, USP-I could be a powerful tool to help world regulatory bodies identify products that are substandard and that should not be allowed within national borders. Comments on USP-I generally have been supportive (5), and USP will carefully consider all comments as the organization continues to work on USP-I with its Board of Trustees and other constituents.

USP's new site in India

At USP's Convention 2005 in March, convention delegates approved Resolution 6, which states that "USP resolves to continue working with inter-national governmental and nongovernmental bodies to increase the impact of its public health programs internationally" (6). A month earlier, USP announced plans to open a site in India, including laboratories, business operations, and a broad range of pharmaceutical services for pharmaceutical manufacturers in India and neighboring countries. This will be the first USP laboratory outside the United States, and, as with USP's domestic facilities, it will be certified to relevant ISO standards. The USP India site will support the activities of Indian and regional partners, including the Indian Pharmacopoeia, to promote the manufacture of good-quality therapeutic products globally. USP will work with Indian manufacturers, as it does with US and multinational firms, to supply safe and effective medicines and dietary supplement ingredients and products. The USP India site will involve experienced Indian scientists in the standards-setting activities of USP, with a focus on off-patent medicines that are legally marketed in the United States.

In early April 2005, USP hired John Hu, PhD, as vice-president, International–China. Dr. Hu will help establish a USP site in China and will be in charge of that operation once it is in place. He currently is president of the Sino-American Pharmaceutical Professionals Association, a nonprofit organization promoting pharmaceutical sciences and business exchanges between the United States and China.

The Spanish translation of USP–NF

USP VIII, USP IX, and USP X were translated into Spanish for distribution in Cuba, Central and South America, and the Philippines. Even with the comparatively small size of the compendia in 1910, 1920, and 1930, the translations did not sell well, partly because of regional differences in the state of healthcare development, partly because of political challenges, and partly because of these nations' historically stronger ties to Spain and Europe.

USP will resume publishing USP–NF in Spanish in November 2005. The work will be a scientifically exact translation of the English version, and, like the latter, will become official on Jan. 1, 2006, with Supplements in February and June (official on Apr. 1, 2006, and Aug. 1, 2006, respectively). The challenges facing the translators were formidable, not only because of the size of the undertaking (USP 28–NF 23's folio runs to 3187 pages), but also because of the need for new terminology (e.g., how does one translate headspace sampling?) and because of regional linguistic variations. Recalling the aphorism that the UK and America are two countries divided by a common language, one can imagine that Spanish in Spain and Latin American countries is not exactly the same.

To resolve technical issues, USP convened an Implementation Group that consisted of volunteers who represented various public health organizations, the pharmaceutical industry, and pharmacy schools in Spanish-speaking countries. Members were selected based on their expertise, understanding of pharmacopeial standards, and linguistic fluency. The team was responsible for translating an initial glossary of commonly used terms in USP–NF into "universal" Spanish to ensure consistency throughout the translation. Then USP contracted with an outside vendor who worked with Spanish-speaking staff and used the glossary to translate the compendia, after which the vendor performed a first-level quality-control accuracy check. A second stage of quality control involved several feedback loops with bilingual scientific liaisons from USP's Department of Standards Development and the vendor to ensure an accurate translation. In the 2005–2010 cycle, USP plans to transition the Implementation Group to an Advisory Panel working with USP's new International Health Expert Committee.

On the basis of lessons learned during this process, USP is considering translating USP–NF into other languages such as Chinese, Russian, and Arabic.

International harmonization

Members at Convention 2005 passed Resolution 7, which calls on USP "to continue its efforts to harmonize compendial standards with the Pharmacopeial Discussion Group (PDG) and other pharmacopeias." USP has long been involved in such activities and looks forward to continuing them during the 2005–2010 cycle. At the same time, USP recognizes the resource constraints associated with harmonization and will work with all stakeholders, under the direction of the USP Board of Trustees, to determine how harmonization should proceed—now that the experiment has proceeded for approximately 15 years. Certainly the global outreach programs outlined above will lead USP to further constructive international interactions.

Conclusion

Space limitations prevent detailed discussion of USP's international programs, which, among other activities, include efforts with the US Agency for International Development to establish drug-monitoring programs in developing nations and work with many other international bodies, including the World Health Organization. Still, this review of USP's international standards-setting activities shows that USP's mission—promoting public health by establishing and disseminating officially recognized standards of quality and authoritative information about the use of medicines and other healthcare technologies—cannot be restricted to the United States. The need for good-quality medicines is universal, and USP is pleased to work internationally to help patients and practitioners, as well as pharmaceutical manufacturers and compounding professionals, meet this urgent need.

Roger L. Williams, MD, is the executive vice-president and CEO of the United States Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790, tel. 301.816.8255. Stefan Schuber, PhD, director of scientific reports at USP, contributed to this column.

References

1. L. Anderson and G.J. Higby, The Spirit of Voluntarism: A Legacy of Commitment and Contribution—The United States Pharmacopeia 1820-1995 (United States Pharmacopeial Convention, Inc., Rockville, MD, 1995), pp. 70–71.

2. Project Team 4, The Reference Standards Committee of the USP Council of Experts and Its Advisory Panel, USP Staff and Consultant, and Council of Experts Chair, "Official USP Reference Standards: Metrology Concepts, Overview, and Scientific Issues and Opportunities," submitted for publication.

3. USP supplies reference standards to 131 countries out of the 177 countries identified by The Economist in its Pocket World in Figures (Profile Books Ltd., London, UK, 1993), p. 9.

4. Council of Experts Executive Committee, Ad Hoc Council of Experts Committee, and USP Staff, "Development of a New Official Compendium, Separate from USP–NF, for Articles Not Legally Marketed in the U.S." Pharm. Forum. 30 (5), 1877–1883 (2004).

5. United States Pharmacopeia staff, "USP-International: Responses to Comments on Stimuli Article," Pharm. Forum. 31 (4), in press (2005).

6. To see a list of all the resolutions approved at Convention 2005, visit the USP Web site at http://www.usp.org/aboutUSP/resolutions.html (accessed Apr. 28, 2005).