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Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.
After a series of structural changes, the author wonders whether USP is undergoing an identity crisis. USP CEO Roger L. Williams responds.
The United States Pharmacopeia (USP) is the oldest continuously revised compendium in the world. Established in 1820, this independent organization has been setting US standards for medicines and pharmaceuticals for more than 185 years. Although FDA recognizes USP standards, the US Pharmacopeial Convention organization was created to be independent from the government, making it the only nongovernmental compendium in the world. The original USP was a collection of recipes to aid pharmacists in formulating medicines for patients. The mission was to produce a book that would allow pharmacists to be able to offer reliable products with consistent names to patients in the United States.
Susan J. Schniepp
At the time the first USP debuted, the pharmaceutical industry did not exist and pharmacists used the information in USP to deliver uniform products to the approximately 7 million residents residing in the 22 states that comprised the US at that time. The original publication contained monograph instructions for 621 items and was updated at approximately 10-year intervals.
The evolution of USP
Today, USP is updated annually and contains more than 4000 monographs in addition to a myriad of general-test and information chapters. USP has more than 550 full-time employees and uses more than 1000 volunteers to set current compendial standards. In a few short years (9 to be exact) USP will celebrate its 200th birthday. USP has much to be proud of.
However, during the past decade, the organization seems to have decided that the patients and pharmaceutical industry of the US are not a big enough arena for its standard-setting activities. USP has changed its mission statement to indicate that it wishes to "improve the health of people around the world through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods" (1). Its current vision is "...to be a leader in promoting the public health by creating a unique knowledge base—consisting of quality standards and information on proper use—for medicines and related products and practices. USP will ensure that people throughout the world have access to this knowledge base" (1).
USP purchased the Food Chemicals Codex and opened offices in Switzerland, India, China, and Brazil. In its October 2008 mid-cycle convention report, USP indicates that the report is intended to inform "...USP's volunteers—members of the USP Convention; Board of Trustees; Council of Experts, Expert Committees, and Advisory Panels; and Stakeholder Forums and Project Teams—of the strides made to date in the 2005–2010 cycle. It offers a snapshot of significant achievements, milestones, and progress toward the goals articulated at the 2005 USP Convention. And perhaps most importantly, it provides a glimpse of where USP is going in the future..." (1).
In addition, at the USP 2010 Convention, the organization passed Resolution 4, which deals with supporting and advancing global public-health initiatives." The resolution states, "Working in consultation and collaboration with national, regional and global stakeholders, USP resolves to assess the feasibility and advisability of advancing global public health initiatives. Where advisable and feasible, USP should seek to expand its resources for these initiatives, building on identified needs and existing opportunities, in order to support its international activities while preserving and fulfilling its role under US law" (1). On USP's website, there is an update regarding this resolution which indicates that USP is expanding its role in India and China as well as exploring relationships with the Association of Southeast Nations and Middle East and North African nations.
Taking on too much responsibility
Although these initiatives are altruistic, this author wonders whether USP is reaching a little too far from home in its pursuit of global pharmacopeial dominance. Perhaps some of these international resources could be redirected to continue and speed up the harmonization of monographs and testing requirements with the European and Japanese Pharmacopeias, a goal that has been on USP's plate for some time. Or better yet, the true altruistic action for this standard-setting body would be to provide the other pharmacopeias assistance, staff, and funding to enhance their national compendia, or to work in a more collaborative manner with the World Health Organization to develop additional monographs for the International Pharmacopoeia.
Disrespecting industry input
One philosophy that has not seemed to change is USP's reluctance to accept that the USP–National Formulary (NF) is a compilation of the hard work and intellectual input of regulatory filings of US proprietary and generic pharmaceutical companies. Representatives from these companies belong to trade organizations. These trade organizations make up the members of USP's Prescription/Nonprescription Stakeholders Forum (PNP–SF). In the May 19, 2011 PNP–SF meeting, USP announced to the attendees that they were re-evaluating the need and purpose of these meetings. USP proposed reducing its interaction with the industry trade organizations that make up the PNP to a once-a-year webinar instead of the current two face-to-face meetings. In addition, USP opened the planning committee for these meetings by posting a call for interested parties on its website and asking these volunteers to nominate a chair person.
If all that wasn't enough, USP summarily dismissed the current PNP–SF industry member's suggestions to form new project teams in an effort to help USP achieve some of its 2010 resolutions and to avoid such issues as the recall of USP 33–NF 28, the monograph redesign project, the confusing implementation of residual-solvents testing, the number of errors in the Pharmacopeial Forum and the potential confusing implementation of the revised USP <231> Heavy Metals General Chapter. These situations have left industry with a sense that USP is losing touch of its responsibility to the US pharmaceutical and medical communities. The only project team that USP intends to keep is the Compendial Process Improvement Team, whose charter is to address how USP can streamline and speed up its process for getting monographs and making information available. What USP fails to recognize is that the majority of the people who are representing the industry at the PNP–SF meetings have scientific backgrounds and can offer constructive and valuable insight regarding technical issues facing the USP.
In summary, there are two issues that are of concern to this author: the apparent globalization of USP without sufficient harmonization and the dichotomous position of wanting the US industry to provide its technical information for monographs but discouraging input when it comes to assisting in improving the scientific information contained in USP. It seems that USP is trying to find a new identity that focuses beyond US borders, an approach that conflicts with what should be USP's main focus: providing current and accurate monographs for use by the US pharmaceutical industry. Let's hope the pharmacopeia can figure out its true identity before it ends up with no identity at all.
Susan J. Schniepp is vice-president of quality at OSO Biopharmaceuticals, firstname.lastname@example.org.
1. USP website, www.usp.org.
The author served on the PNP–SF and on a USP expert committee from 2000 to 2005. She chaired a USP expert committee from 2005 to 2010.
* See USP's response on next page
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