Public Comment and Expert Oversight: The Cornerstones of USP Standards Development

Since its inception in 1820, the US Pharmacopeia (USP) has developed authoritative, credible, publicly available standards for medicines, dietary supplements, and related products. Then as now, a lack of consistency in how medicines were prescribed, prepared, dispensed, and administered posed a risk to public health. Our mission has always been to promote public health and to benefit health professionals, patients, and consumers by seeking to establish purity and consistency. This is no small task.

Todd L. Cecil

To meet the challenge, USP exercises a vigorous standards-setting process that draws on both public comments and meticulous scientific review. As an independent organization, USP does not have the authority to compel submission of information for standards. Rather, we have worked hard to build relationships with pioneer and generic pharmaceutical manufacturers and experts, many of whom have a strong appreciation for the value of public quality standards. Over time, these (and many other) relationships have allowed the number of monographs in the US Pharmacopeia to grow from the original 1820 tally of 621 to the current total of over 4000.

The worldwide array of pharmaceutical manufacturers and experts who choose to participate in this effort provide proposed new monographs, General Chapters, and a wealth of data. But that's just part of the story. In addition to industry cooperation, public input and interaction are vital to the development of USP standards. Once materials are received, USP's scientific staff and volunteer experts review the input, conduct laboratory tests, where necessary, and then publish the proposals in Pharmacopeial Forum—USP's bimonthly journal of standards development and compendial review—for public comment. A USP Expert Committee subjects all comments to scientific scrutiny before making the recommendation to publish a standard in the US Pharmacopeia–National Formulary (USP–NF). To further ensure transparency, all communications with USP regarding standards become a matter of legal record.

This public process helps refine and finalize information before its official publication in USP–NF. It is important to note that the volunteer experts are themselves vetted for scientific knowledge and expertise in an open and competitive election process at USP's five-year convention. Expert Committee members serve as unbiased volunteers under strict conflict-of-interest and confidentiality regulations. The combination of fully available public commentary and highly qualified expert oversight ensures both rigor and a broad range of scientific input. For a public standard to be credible, this two-fold approach is key to establishing confidence.

An explanation is never as clear as an actual example. Consider the progress of General Chapter ‹797› Pharmaceutical Compounding–Sterile Preparations, which is currently headed toward official publication in USP–NF (at a date still to be determined). The last time ‹797› was revised, USP did so entirely through the efforts of staff working with volunteer experts. The practitioner community was not involved, not by intent but because compounding pharmacists tend not to be subscribers of USP–NF. The Sterile Compounding Expert Committee, responding to growing concern about the quality and consistency of compounded preparations, revised the 1995 General Chapter ‹1206› Sterile Products for Home Use. The revisions were extensive and included the renumbering of the General Chapter to ‹797›. This is significant, of course, because it moved the General Chapter from informational (those numbered over ‹1000›) to enforceable (those numbered under ‹1000›). The impact was even greater given the growing importance of compounding as a means of tailoring a drug dose to an individual patient, or in replacing a discontinued manufactured drug.

Following publication in 2004, as practitioners realized the effect of the revised, now-enforceable General Chapter ‹797› on their daily work, there was a surge of input that had not initially been solicited— about 2000 comments. This outpouring underscored the importance of public comment as well as expert review, and USP started the current revision cycle as quickly as possible. This time we did it quite differently: We held briefings for 16 stakeholder organizations, plus a stakeholder forum meeting. About 60 compounding professionals and other interested parties attended, and we held Webinars for those who could not be there in person. At these sessions, staff reviewed proposed changes and actively sought stakeholder input. In addition, we provided an online mechanism to view and comment on proposed changes to ‹797›. Through these outreach efforts, we got hundreds of comments that went into the revision process.

This marked a first-time, singular outreach program for USP. Why did we go to such lengths? In short, the response of the compounding community to the initial lack of inclusion reminded USP-staff and volunteer experts alike that not actively providing channels for public comment is neither in the interest nor the tradition of USP standards setting. The current revision cycle of General Chapter ‹797›, based on extensive interactions among USP staff, volunteer experts, and the compounding community, is fully supportive of USP's core mission of objective science and transparency. Inclusion can sometimes be messy and it can take time—you'll note that ‹797› has yet to be finalized in official publication. But it will be published, as a result of the kind of dialogue between public and experts that has characterized USP standards setting for nearly 200 years.

I urge members of the extended pharmaceutical community to participate in this well-established, respected, and effective process. Thorough instructions are available on the USP Web site, at www.usp.org/USPNF/, and a diagram illustrating the standards revision process is published in the front matter of every issue of Pharmacopeial Forum. Your participation will help keep the process a model of scientific integrity, thereby helping to ensure good pharmaceutical care for all.

Todd L. Cecil is the vice-president of the Department of Standards Division at the US Pharmacopeia, tlc@usp.org