The Value of USP Public Standards for Therapeutic Products

The word pharmacopeia means to make a drug. Before the Food and Drug Administration (FDA) and modern pharmaceutical manufacturing, virtually all medicines in the United States were prepared by physicians or pharmacists. Medicines were prepared in the early years of the Republic according to a number of publications—pharmacopeias and dispensatories—from this country and abroad. These differing approaches, coupled with the absence of laws regulating either the practice of medicine and pharmacy or the medicinal preparations used, led to irregularities in how medicines were prescribed, prepared, dispensed, and administered. This lack of consistency was widely recognized then, as it is now, as a barrier to quality medical care. It prompted agreement by a group of physicians to create a national pharmacopeia. These physicians held the first United States Pharmacopeial (USP) Convention in 1820 in the Capitol Building of the United States (1). Delegates representing regional medical societies and schools arrived in Washington, D.C., to determine the contents of the first Pharmacopoeia of the United States of America (USP), which presented the best medicines, named and provided recipes for their preparation, and gave instructions for their use. Over time, with the rise in modern pharmaceutical manufacturing, the task of making a drug has shifted from practitioners to pharmaceutical manufacturers. A residuum of the original approach remains with practitioners who compound a medicine, using at times a USP preparation monograph pursuant to a physician’s prescription. But only a relatively small fraction of prescriptions in the United States are compounded. USP was incorporated under the laws of the District of Columbia in 1900. It is a 501(c)(3) corporation working in the public interest. The USP Convention meets at 5-year intervals, when it elects its governing body, the Board of Trustees, and its standards-setting body, the Council of Experts. With staff support, the Council of Experts creates the content for the United States Pharmacopeia–National Formulary (USP– NF). With the exception of staff, all participants in USP, the convention members, members of the Board of Trustees, and the Council of Experts work as volunteers. USP has strict conflict-of-interest rules and also confidentiality rules that protect sensitive commercial and trade secret information that is provided by sponsors of monograph and General Chapter proposals. Although several public health laws controlling biologicals and drugs were created in the early part of the twentieth century in the United States, modern regulatory control really began with passage of the Federal Food, Drug, and Cosmetic Act (FFDCA) in 1938. This act incorporated prior legislation and created the FDA. FDA regulates pharmaceutical manufacturing closely. USP–NF has evolved in concert with these changes to become a book of public standards. The modern pharmacopeia is presented as two compendia, the original USP and, more recently, the NF. In 1975, USP purchased the NF, a compendium of public standards primarily for excipients. These are now published annually as a combined text, USP–NF, with two annual Supplements. The current edition, USP 27–NF 22, became official in January 2004 and contains monographs for prescription and over-the-counter (OTC) drugs, biologicals, dietary supplements, and allied therapeutic products (including some devices). Excipient monographs continue to appear in NF. The two compendia are named in the FFDCA as official compendia of the United States (2). The FFDCA integrates USP standards in the adulteration and misbranding provisions for drug products. Section 501(b) of the act provides that a drug is adulterated if it is recognized in USP–NF and does not adhere to USP–NF standards or does not state on the label how the drug strength or purity differs from these standards. Section 502(g) of the act states that a drug is misbranded if it is recognized in USP–NF and does not meet USP–NF packaging and labeling requirements set forth. Section 502(e) requires that the established name of the drug must appear on the label and states that the established name of a drug or ingredient is the one appearing in USP–NF. The modern USP–NF now comprises more than 4000 monographs for named ingredients and products, which are termed articles, as in articles of commerce. This is also how 1 United States Pharmacopeia, Rockville, Maryland 20852, USA. 2 J. P. Boehlert, E. M. Cohen, J. E. DeMuth, M. C. Frederiksen, H. G. Klein, R. M. Russell, P. L. Schiff, S. S. Seaver, A. M. M. Shepherd, S. Stavchansky, T. J. Wozniak, and Dr. Williams (ex officio chair). 3 To whom correspondence should be addressed. (e-mail: rlw@ usp.org) Pharmaceutical Research, Vol. 21, No. 10, October 2004 (© 2004)