USP’s Response: USP in a Global Era
Roger L. Williams
To fulfill its role as developer of official standards for medicines quality in the United States, the US Pharmacopeial Convention
(USP) has looked past US borders, as have manufacturers and FDA. Globalization of the pharmaceutical industry has altered
the ways industry, regulators, and pharmacopeias interact, and USP is engaging the industry as it exists today. Concerns have
been raised about USP’s global operations and possible effects on efforts to harmonize and modernize monographs in the US Pharmacopeia–National Formulary (USP–NF). Additionally, there are concerns about USP’s engagement with the USP Prescription/Nonprescription Stakeholder Forum (PNP–SF).
I will touch on these in order.
Roger L. Williams, MD
Globalization and harmonization
Most of USP’s energies and resources go to its US compendia, particularly to USP–NF. Investments during the past several years have been to advance our laboratories, moving from less-than-adequate space and
equipment to state-of-the-art facilities and equipment in our Maryland headquarters, India (where a large new building has
just opened), China (expansion under consideration), and Brazil. All of these laboratories support the work of the Council
of Experts, USP’s standards-setting body, specifically to make available public reference materials that are critically needed
for procedures in USP–NF monographs. USP has devoted considerable energies to better understanding basic measurement science (metrology) imperatives
so that all parties—particularly FDA—have access to modern monographs and reference materials.
Given the global nature of pharmaceutical commerce, pharmacopeial harmonization is indeed important. Yet the outputs of the
Pharmacopeial Discussion Group (PDG) have not met expectations. (PDG represents the pharmacopeias of Europe, Japan, and the
US, and aims to achieve compendial harmonization.) PDG has focused on a narrow slice of standards: excipient monographs and
the International Conference on Harmonization (ICH) Q6A-based General Chapters Q6A on test procedures and acceptance criteria
for new drug substances and new drug products. After more than 20 years, only 63 excipient monographs of more than 300 in
NF, and about 20 General Chapters have been harmonized. NF is missing 137 monographs and many of the remaining ones require updating, including those that have moved through PDG harmonization.
Of approximately 1200 excipients in global commerce, most have no public standards. PDG excludes major countries and regions,
notably China and India, Latin America/Caribbean, and Middle East/North Africa.
Other initiatives are needed, and USP is taking a first step, we hope with other pharmacopeias. We are working with the World
Health Organization (WHO) and national and regional pharmacopeias to conduct summits around the world. China has embraced
the concept, and will host its second Global Pharmacopeial Summit in Beijing in mid-November. USP hopes a late-2012 culminating
meeting, convened by WHO, will pave the way for new thinking on pharmacopeial harmonization. Additionally, USP’s new Medicines
Compendium may model a path to more flexible pharmacopeial monographs using performance-based approaches.
USP has worked with industry for more than a century to include monographs in USP–NF that mirror FDA approvals. USP greatly appreciates these donations of time, information, and materials from our industry
colleagues. We believe every drug needs a public monograph and reference material the moment it enters the market, allowing
FDA and other regulatory authorities to check for adulterated, counterfeit, or substandard medicines and their ingredients.
USP wishes to work with all manufacturers to gain needed information and materials to support public standards.
But we cannot overlook the numbers: monographs in USP–NF number more than 4000, yet it is missing nearly 1900. Many need updating. Deficiencies in USP’s heparin monographs provided
an example of why public health is best served by modern monographs—and USP worked carefully with FDA and industry to update
these critically needed standards. FDA has identified monographs in USP–NF needing improvement; we welcome this input. We have recently received good support from the Consumer Healthcare Products
Association, and welcome similar support from other associations.
PNP Stakeholder Forum
USP values the talented representatives from pharmaceutical manufacturers who have worked to advance topics through the PNP–SF
since 2000. This has proved an important venue where issues have been discussed and many resolved. In recent years, opportunities
for stakeholder input into USP standards have increased significantly, including new expert panel rules allowing experts to
fully participate in deliberations without having to abstain due to conflict. A new “design phase” approach—which emanated
directly from the PNP–SF—uses workshops, webinars, etc., for stakeholders to provide early input into USP standards.
USP spoke about ways to expand the forum’s reach at the May 2011 meeting. We focused on two principles: USP will conduct its
standards-setting activities in an open, transparent manner that allows participation by all constituencies; and because USP
text and publications may have legal implications in the US and elsewhere, their language must stand on its own and not be
interpreted to a few, thereby disadvantaging parties without that interpretation. All stakeholders should have same opportunity
to participate in USP’s stakeholder activities, so that a select group does not have disproportionate voice. Thus, we are
exploring conducting the PNP–SF in a format that can be open to more stakeholders: web meetings. But at the PNP stakeholders’
request, we may continue to conduct face-to-face meetings while enabling web access. We hope to provide enhanced ability for
others to participate, including shaping agendas and participating in project teams.
As noted, there are crucial issues for consideration. These include the role of the pharmacopeia in a modern, democratic society
as a means of advancing modern public standards; the challenge of keeping USP–NF monographs up-to-date and USP’s reliance on industry support for this; and the need for pharmacopeias to come together so
that patients and practitioners everywhere have access to good quality medicines. If industry, FDA, and USP address these
issues adequately and together, they can be resolved. PT