LABORATORY PROFILE Applied research at USP Go to any drugstore, and more than 90% of the pharmaceutical products that you'll find in the aisles or behind the pharmacy counter will have a monograph in the U.S. Pharmacopeia (USP), a compendium of standards, specifications, analytical methods, and pharmacy-related information. This compendium, along with the National Formulary (NF), is published by USP Convention, a private, nonprofit organization that is unique among the national pharmacopeias in that it is the only one that is not part of its government. Although the USP was founded in 1820, its laboratory was not added until 1975, when the USP bought the assets of the Drug Standards Laboratory. "USP is not a compliance organization, so testing marketed products for adherence to USP standards is not part of the laboratory's mission," says Richard Lindauer, director of the USP Drug Testing and Research Laboratory in Rockville, MD. USP is not involved with drug approvals: USP's work in developing a monograph doesn't begin until the FDA has approved the drug for marketing. The lab's role What, then, does the laboratory do? The lab's workload is primarily organic analytical chemistry, emphasizing applied research. The laboratory, a component of USP's Division of Standards Development, provides the analytical capabilities and expertise to answer questions raised by the Committee of Revision, the portion of the USP organization that is responsible for the scientific content of the compendia. Anyone may submit changes to the content of the USP or the NF, but these must be approved by the Committee of Revision. If insufficient validation data accompany
quest to properly judge the proposed change, the lab may be called on to provide the missing information. However, method validations are only a small fraction of the work performed by the laboratory. According to Lindauer, more than 70% of the lab's workload involves collaborative studies to evaluate the identity and purity of USP's chemical reference standards collection (more than 1450 compounds). Unlike AOAC International collaborative studies, USP's collaborative studies give the participating entities—the USP lab, FDA and other collaborating groups—the freedom to select the most appropriate techniques. Given the types of samples that the lab usually evaluates, the scientists find themselves regularly performing TLC, LC, UV-vis IR wet chemical and elemental analyses (The laboratory also performs MS CE Raman polarized-light microscopy optical rotation analysis thermal analysis and dissolution testing)' Lindauer says that although the Reference Standards Department receives information about identical samples from all participants, the USP lab works in isolation when testing reference standards. "We have an agreement that we don't see the other labs' results until we're done with our work. The main product of the laboratory is its scientific reports, which are peer-reviewed and written to publication standards prior to being released to the Committee of Revision." Lindauer says, "Nearly every one of our projects is a one-of-a-kind thing. It may be similar to something that we've done before, but even a reference standard project where we're doing LC, TLC, IR, GC, and moisture determination—which may have the illusion of being routine—is done on a material either new or that we probably haven't seen in the last few years, on equipment that may not have been used the last time, by people who may not have done the test before, and frequently by completely new methods. Imagine the difficulties of QC lab for 1450+products under those conditions!" Despite the deceptively routine nature, the laboratory's analyses do not lend themselves to automation because each sample might require different instrumental conditions. Thus, in stark contrast to many QC laboratories,
fully one-third of the staff have advanced degrees (M.S. or Ph.D.); the rest have bachelor's degrees. Lindauer praises the USP for its generosity in providing personnel and space for the laboratory. When Lindauer signed on as lab director in 1982, only 17 people worked in the laboratory. The laboratory now has a budget for 35 scientists and has expanded its bench space several times. Uncharted territory The newest trail for the USP laboratory to blaze is in the realm of botanically derived dietary supplements—such as ginger and valerian—that are not currently considered drugs but that experts have recognized as having some medicinal properties. The laboratory has been asked to investigate such natural products because USP Convention wants the Committee of Revision to explore the feasibility and advisability of setting standards for these materials. This is an area that will require extensive research, says Lindauer. "In many cases, we're not sure what the active ingredients are. There are so many variables that can impact the quality of a botanical material: geographical source, time of year, or exact part of the plant used. Answering the simple question 'Is this material good enough to be a USP reference standard?' becomes a major problem." With uncharted territory ahead, the Drug Testing and Research Laboratory's role keeps expanding. How long will that last? Lindauer says, "The reality is that USP has a lot of interests, and staff needs are growing in a number of areas. The laboratory will continue its mission to provide the objective, scientifically valid information to the Committee of Revision in support of USP's mission to promote the public health." Celia Henry
Analytical Chemistry News & Features, March 1, 1997 163 A
