This section provides background information on the United States Pharmacopeial Convention (USP), as well as general information about the 29th revision of the United States Pharmacopeia (USP 29) and the 24th edition of the National Formulary (NF 24). Additional official information about the specific uses of these texts is provided in the General Notices and Requirements (page 1).

USP 29–NF 24— USP 29–NF 24 text is official as of January 1, 2006, unless otherwise noted. USP–NF contains official substance and preparation (product) monographs. An official substance and an official preparation are defined in the General Notices of this Pharmacopeia. USP 29–NF 24 contains science-based standards for therapeutic products, as presented by decisions of the Council of Experts. USP 29–NF 24 monographs also are useful to both pharmaceutical manufacturers and compounding practitioners. With few exceptions, all articles for which monographs are provided in USP 29–NF 24 are legally marketed in the United States.

Organization of USP 29–NF 24— Monographs for active ingredients and preparations—with the exception of dietary supplements—appear in the first section of USP. Monographs for dietary supplements appear in a separate section of USP. General Chapters specific to dietary supplements are included in numerical order with the rest of the General Chapters in USP. Excipient monographs usually are presented in NF but also may appear in USP with suitable cross-referencing when they are also drug substances. A tabulation of excipients by functional category appears on page 3257.

Revisions— USP–NF is continuously revised. Revisions are presented annually, in twice-yearly Supplements, in Interim Revision Announcements (IRAs), and in Revision Bulletins (on the USP Web site).

Supplements— The First Supplement to USP 29–NF 24 will be published in February 2006 and will become official in April 2006. The Second Supplement will be published in June 2006 and will become official in August 2006. Users of USP print products must retain both Supplements and keep their subscriptions current in order to have up-to-date information. The Index in each Supplement is cumulative and includes citations to the annual revision and, for the Second Supplement, citations to the First Supplement. The contents of the two Supplements are integrated into the annual edition of the following year, along with new official revisions since the Second Supplement to the previous compendia.

Interim Revision Announcements— IRAs contain revisions that become official in the interval between publication of the annual revision and Supplements. They appear in USP's bimonthly journal, Pharmacopeial Forum (PF), with the official date noted in the publication. They are subsequently incorporated into the next Supplement or annual revision. One reprint of each IRA is available to USP–NF subscribers on request. Additional copies may be ordered from USP.

Pharmacopeial Forum— The Policies and Announcements section provides information about publication and comment deadlines, USP news, and summaries of issues discussed by the Council of Experts and its Expert Committees. Proposals for revision are presented either as Pharmacopeial Previews or In-Process Revisions. Previews focus on monographs and General Chapters at an early stage of consideration. They also present new monographs for controversial items needing a longer public comment period. Depending on public comment, a Preview proposal may or may not advance to the in-process revision stage. In-Process Revisions represent final draft documents that are expected to advance to official status.

Symbols Indicating Change to Official Text— Symbols identify the beginning and end of each revision. For Supplements, a black square superscript marks the beginning of each revision, and a black square subscript marks the end. For the six yearly Interim Revision Announcements, black circles are used. Next to the subscript is a number that links the official date of the revision with the corresponding Supplement or Interim Revision Announcement. For example, a black square subscript with the numeral 1 next to it indicates that the revision will become official via the First Supplement. [NOTE—When Interim Revision Announcements are incorporated into the next Supplement or annual edition, the black circles will be replaced with either the appropriate Supplement black square and number or annual edition triangle and number.] The following table shows symbols and official dates for Interim Revision Announcements and Supplements to USP 29–NF 24:

Chemical Names and CAS Registry Numbers— Chemical subtitles given in the monographs are index names used by the Chemical Abstracts Service (CAS) of the American Chemical Society. They are provided only in monographs in which the titles specify substances that are definable chemical entities. The first subtitle is the inverted form of the systematic chemical name developed by CAS. This is presented in accordance with the rules established over the years by the International Union of Pure and Applied Chemistry (IUPAC) and the International Union of Biochemistry, and this form is employed in the current issues of Chemical Abstracts (CA). The second subtitle, given in uninverted form, is of a systematic type formerly used in CA. It is identical with, or closely resembles, the chemical name sanctioned and employed by IUPAC and by the World Health Organization (WHO). IUPAC names make generous use of nonsystematic and semisystematic (often referred to as “trivial”) names and qualifying terms, all of which impede electronic manipulation. In contrast, CAS names are fully systematic for most substances and are amenable to search and retrieval. The two subtitles referred to above are frequently identical, and a CAS synonym is occasionally supplied as a third subtitle. Monographs with chemical subtitles generally also carry CAS registry numbers. These italicized, bracketed numbers function independently of nomenclature as invariant numerical designators of unique, unambiguous chemical substances in the CAS registry and thus find wide, convenient use.

USP 29–NF 24 Spanish Edition— In response to the growing need of Spanish-speaking pharmaceutical scientists and professionals, the USP–NF will be available in an official Spanish edition for 2006. USP has used the most rigorous translation and quality control to develop the USP–NF in Spanish. The translation process was guided and directed by a special advisory group of volunteer scientific experts from many Spanish-speaking countries. The translation was thoroughly checked by bilingual (English/Spanish) USP staff scientists.

Print and Electronic Presentations— All USP publications are available in print form. In addition, USP–NF and its two annual Supplements are available in compact disc (CD) and Internet versions. The CD version makes USP–NF accessible to users on their computer hard drives. The Internet format allows individual registered users to access the online format through the World Wide Web. Both electronic formats provide fast and easy access to official USP–NF content, along with extensive search options. The electronic formats are cumulatively updated to integrate the content of Supplements. Searchable electronic versions of PF and of the USP Dictionary (see below) also are available.

Chromatographic Reagents— This comprehensive reference provides detailed information needed to conduct chromatographic procedures found in USP–NF. Chromatographic Reagents lists the brand names of the column reagents cited in every proposal for new or revised gas- or liquid-chromatographic analytical procedures that have been published in PF since 1980. Chromatographic Reagents also helps to track which column reagents were used to validate analytical procedures that have become official. The branded column reagents list is updated bimonthly in PF.

USP Pharmacists' Pharmacopeia— The USP Pharmacists' Pharmacopeia is the first dedicated reference from USP for pharmacy practitioners and students. Compiled under the guidance of leading pharmacy experts, this reference provides comprehensive and critical information that will enhance the knowledge and application of pharmacy practices. The USP Pharmacists' Pharmacopeia combines pharmacy-relevant verbatim extracts from the USP–NF as well as other authorized reference information developed by USP's Council of Experts. The relevant USP–NF requirements in monographs and General Chapters are enforceable by regulatory authorities. The USP Pharmacists' Pharmacopeia will be available in two formats: print and online.

USP Dictionary— The USP Dictionary of USAN and International Drug Names provides the most up-to-date United States Adopted Names of drugs; official USP–NF names; nonproprietary, brand, and chemical names; graphic formulas; molecular formulas and weights; CAS registry numbers and code designations; drug manufacturers; and pharmacologic and therapeutic categories—all in a single volume. The Dictionary helps to ensure the accuracy of product labeling; reports, articles, and correspondence; FDA regulatory filings; and pharmaceutical package inserts. It is published annually (latest edition April 2005) and is recognized by FDA as the official source for established drug names. (See Nomenclature section below.)

Reference Standards Catalog— The catalog listing the collection of official USP–NF Reference Standards is kept up-to-date via bimonthly publication in PF. It also can be accessed on the USP Web site at www.usp.org and is available in print form by contacting USP Sales and Marketing staff at 301-816-8237. The listing identifies new items, replacement lots, lots of a single item that are simultaneously official, lots deleted from official status, and a preview of items eventually to be adopted. Purchase order information is included, and the names of distributors who can facilitate international availability of these items are suggested. This program benefits from the widespread voluntary contribution of suitable materials and test data from pharmaceutical manufacturers. USP advances this unofficial material to official status via careful characterization studies and collaborative testing, followed by review and, if appropriate, approval by the Reference Standards Committee of the Council of Experts. Use of these official USP–NF Reference Standards promotes uniform quality of drugs as an aid to the public health.

USP Convention— USP's direction and priorities are determined by more than 400 credentialed Convention members divided into nine categories (page xxvi). Within each membership category, each eligible organization is invited to appoint a representative. Membership composition is determined so as to ensure suitable representation of those sections of the health care system that are influenced by, and in turn influence, USP's activities. Darrell R. Abernethy, M.D., Ph.D., Chief of the Laboratory of Clinical Investigation at the National Institute on Aging, is the USP Convention President for 2005–2010. Convention members elect USP's officers and trustees and the Council of Experts. They also vote on resolutions to guide USP's scientific policy and public health initiatives.

Board of Trustees— USP's Board of Trustees is entrusted with management of the business affairs, finances, and property of USP. During its five-year term, the Board defines USP's strategic direction by its key policy and operational decisions. A listing of the members of the 2005–2010 Board of Trustees appears on page xvi.

Council of Experts— The Council of Experts is the standards-setting body of USP. It is composed of 56 Expert Committee chairs elected to five-year terms by USP's Convention in April and July 2005. A Nominating Committee, consisting of the Chair of the Council of Experts, the Convention President, and the Vice-Chair of the Nominating Committee for the Council of Experts, nominated individuals who are subsequently elected by the members of the Council of Experts. The chairs and committee members consist of more than 500 volunteers drawn from all parts of the world. The Expert Committees in the Standards Division are responsible for the content of USP–NF (see Figure 2) and have been informally grouped into Collaborative Groups of common interest, and the Information Division has been organized under its own Executive Committee. The Council of Experts' Executive Committee (see page xii) provides overall direction, is an appeals body, and performs other functions that support the Council's operations. Forty of the 56 Expert Committees are responsible for the content of USP–NF and associated publications.

Advisory Panels to the Council of Experts— The Chair of the Council of Experts, Dr. Roger Williams, periodically appoints expert advisory panels to assist the Council of Experts in reaching scientific decisions and implementing new USP directives relating to USP–NF. A listing of Advisory Panels is on USP's website.

Stakeholder Forums, Project Teams, and Quality Communication Groups— USP formed several Stakeholder Forums, Project Teams, and international Quality Communication Groups during the 2000–2005 cycle as a means of enlisting the active participation of stakeholders interested in a specific standards-setting topic. Depending on the topic, a Stakeholder Forum may form Project Teams to work more intensively on selected topics in an advisory capacity. As part of its efforts to work internationally with users of USP products and services, USP has also formed country-oriented quality communication groups, which function as non-U.S. stakeholder forums. USP's Quality Communication Groups are a channel for USP to reach out globally to industry, professional, and other associations that have a stake in drug product quality. The groups promote direct relationships with USP's scientific and technical activities. The following are lists of Stakeholder Forums and Quality Communication Groups continuing in the 2005–2010 cycle.

Quality Communication Groups

Staff— USP maintains a staff of nearly 400 scientists, professionals, and administrative staff at its Rockville, Maryland, offices. A primary activity of many of these staff members is to assist the Council of Experts in producing USP's publications. A full listing of all USP employees is provided, beginning on page xx, after the names of Expert Committee members. Users of USP–NF who have questions about the organization, its publications, USP Reference Standards, or general questions are referred to listings in PF, which are updated bimonthly.

Governing Documents— USP–NF standards are recognized widely because they are authoritative and science-based and are established by a transparent and credible process. The organization's Articles of Incorporation, Constitution and Bylaws, and Rules and Procedures of the 2005–2010 Council of Experts appear in Appendices A, B, and C, respectively. These documents serve as the governing principles for USP volunteers and staff.

Conflicts of Interest— USP's Conflict of Interest provisions require all members of the Council of Experts, its Expert Committees, Ad Hoc Advisory Panels, Board of Trustees, and key staff to disclose significant financial interests in companies or other entities that are subject to USP–NF standards or that may be affected by USP–NF information. Members of the Board of Trustees, Council of Experts, and related bodies are not allowed to vote on any matter in which they have a conflict of interest or the appearance of a conflict of interest.

Confidentiality and Document Disclosure— Members of the Council of Experts, Expert Committees, and Ad Hoc Advisory Panels sign confidentiality agreements, in keeping with the confidentiality provisions of the Rules and Procedures of the Council of Experts. The USP Document Disclosure Policy, available on USP's Web site, contributes to the transparency of the standards-setting process by making information available to the public, yet provides protection to manufacturers and others who submit confidential information to USP.

Authority for Publication— USP–NF is published in accordance with Chapter VI, Section 8, of the USP Bylaws, which states, “The Board of Trustees shall authorize the revision and release of text to the United States Pharmacopeia and the National Formulary. Upon approval of the content by the Council of Experts, in accordance with the rules and procedures adopted under Section 9, the Board of Trustees shall then act upon releasing the text and upon designating the date when it is to become official, said date to be reasonably distant from the date of its release. The Executive Vice President–CEO shall, annually or more frequently, upon specific request of the Board of Trustees, certify that the information contained in the United States Pharmacopeia, National Formulary, or other authorized publications have been prepared in accordance with the rules and procedures under Section 9.”

Public Participation— Although USP's Council of Experts is the ultimate decision-making body for USP–NF standards, these standards are developed by an exceptional process of public involvement and substantial interaction between USP and its stakeholders, both domestic and international. Participation in the revision process results from the support of many individuals and groups and also from scientific, technical, and trade organizations.

Working with the Food and Drug Administration (FDA)— USP works with FDA in many ways to promote good communications and optimal interactions. Senior management of both organizations can meet to provide oversight to these activities. FDA's Observer Program that allows FDA representatives to participate in Expert Committees allows continuing interactions between FDA scientific staff and these Committees. FDA staff also may participate on their own time as members of Expert Committees. Staff in the Centers who are responsible for review of compendial activities provide specific links and opportunities for exchange of comments. Mr. Larry A. Ouderkirk in the Center for Drug Evaluation and Research provides a primary link between FDA and USP.

Outreach to Organizations— Revision of USP–NF, particularly in development of new monographs, General Chapters, and specifications for specialized products, continues to progress through the strong and proactive participation of manufacturers, compounding professionals, and many others. USP acknowledges the importance of this participation, which occurs not only through Stakeholder Forums, but also through collaborative activities, work on Project Teams, and many other points of contact. In addition, USP offers assistance to the industry in the development and presentation of new monographs and requests for revision.

Recognition of USP–NF— USP–NF is recognized by law and custom in many countries throughout the world. In the United States, the Federal Food, Drug, and Cosmetic Act of 1938 (FD&C Act) uses the term “official compendium” to refer to the official USP, the official NF, the official Homeopathic Pharmacopeia of the United States, or any supplement to them. FDA may enforce compliance with official standards in USP–NF under the adulteration and misbranding provisions of the FD&C Act. These provisions extend broad authority to FDA to prevent entry to or remove designated products from the United States market based on standards in USP–NF.

Drugs— USP's goal is to have substance and preparation (product) monographs for all FDA-approved drugs. USP also develops monographs for therapeutic products not approved by FDA; e.g., pre-1938 drugs, dietary supplements, and compounded preparations. The complex set of procedures that results in validation of private regulatory procedures submitted in regulatory filings and the subsequent transition to a public official procedure in USP–NF, coupled with availability of a verified reference standard material, has been described elsewhere (T. Layloff et al., The U.S. FDA Regulatory Methods Validation Program for New and Abbreviated New Drug Applications, Pharm. Technol. and Biopharm., January 2000). Although submission of information needed to develop a monograph by the Council of Experts is voluntary, compliance with a USP–NF monograph, if available, is mandatory.

Biologics— In the United States, some biologics are regulated under the provisions of the Public Health Service Act (PHSA). Biologic products regulated under the PHSA are required to bear “proper” names, not “established” names, like drugs. Provisions of the FD&C Act apply to biological products regulated under the PHSA. For this reason, products approved under the PHSA should comply with the adulteration and misbranding provisions of the FD&C Act at Section 501(b) and 502(g) and, thus, should conform to official monographs, if available.

Medical Devices— Section 201(h) of the FD&C Act defines a device as an article/instrument, apparatus, or component recognized in USP–NF. Section 502(e) defines the established name of a device in the absence of an FDA designation of the official name as the official title in an official compendium. Despite these statutory provisions, there is no comparable recognition of USP's standards-setting authority and ability to define a medical device as exists for other FDA-regulated therapeutic products. Under the Food and Drug Administration Modernization Act, the Center for Devices and Radiological Health recognizes national and international standards, including some USP tests and assays for medical devices.

Dietary Supplements— As with drugs and biologics, the Dietary Supplement Health and Education Act amendments to the FD&C Act name USP and NF as official compendia for dietary supplements. For this reason, a dietary supplement may be deemed misbranded if it is covered by a monograph in an official compendium, is represented as conforming to this monograph, and fails to conform. The dietary supplement manufacturer must assert conformance to a USP–NF dietary supplement monograph in order for the compendial standards to apply. This is in contrast with a pharmaceutical product, wherein conformance is mandatory without need for assertion.

Compounded Preparations— Preparation monographs provide information or standards applicable in compounding. Compounding means the preparation, mixing, assembling, packaging, or labeling of a drug or device or other article, as the result of a practitioner's order or in anticipation of such an order based on routine, regularly observed prescribing patterns. Standards in USP–NF for compounded preparations may be enforced at both the State and Federal levels, e.g., if a practitioner writes a prescription for a compounded preparation that is named in a USP–NF monograph, the preparation, when tested, must conform to the stipulations of the monograph so named.

Nomenclature— In the U.S., FDA has authority to establish names for drug ingredients and determine proper names for biologics. FDA executes this work in part through efforts of the United States Adopted Names (USAN) Council. USP participates in this activity, together with the American Medical Association, the American Pharmacists Association, and FDA. Drug product names can be established by FDA, but more often they are developed cooperatively with USP in activities of the Council of Experts' Nomenclature Expert Committee. Oversight of brand names is the responsibility of FDA, working with applicants. The USAN Council's program began in 1961 by providing ingredient names for drugs prior to their marketing. The Council's output is incorporated, along with other names for drugs (including generic, proprietary, and chemical names and code designations), in the USP Dictionary of USAN and International Drug Names. Since 1988 this publication has been recognized by Federal regulation as the source of established names for drugs in the United States. The USP Drug Nomenclature Committee was formed in 1986 to supplement the Executive Committees of the Drug Standards Division and the Information Division and to prevent any inconsistency regarding nomenclature. Following the 2000 meeting of the USP Convention, the responsibility for devising and, when necessary, revising labeling requirements was delegated to this Committee, which is now named the Nomenclature Expert Committee. The Committee's work does not overlap that of the USAN Council. Rather, it is complementary and is concerned with standardization of compendial names, particularly dosage form names, and names for combination drug products.

World Health Organization (WHO)— USP works with WHO in many of its normative and other activities that promote the availability of safe, effective, and good-quality medicines. By invitation, USP staff participate as members or observers of WHO's expert advisory committees, including the Expert Committee for Specifications for Pharmaceutical Preparations and the Biological Standards Expert Committee.

Pan American Health Organization (PAHO)— USP works with PAHO in many of its activities. USP participates actively in PAHO's Pan American Network for Drug Regulatory Harmonization (PANDRH). In this activity, USP attends meetings of the PANDRH Steering Committee as a nongovernmental observer. USP is coordinator for the Pharmacopoeial Working Group (PWG) and is a member of the Bioavailability/Bioequivalence Working Group in PANDRH. The PWG is composed of representatives from the Argentine, Brazilian, Mexican, and United States pharmacopeias. More recently USP also joined the Good Laboratory Practices Working Group.

Pharmacopeial Discussion Group— USP harmonizes pharmacopeial excipient monographs and General Chapters through the Pharmacopeial Discussion Group (PDG), which includes representatives from the European, Japanese, and United States Pharmacopeias, and WHO (as an observer). According to the PDG definition, “a pharmacopeial general chapter or other pharmacopeial document is harmonized when a pharmaceutical substance or product tested by the document's harmonized procedure yields the same results, and the same accept/reject decision is reached.”

United States Agency for International Development (USAID)— USP works to support USAID's global health objectives by providing leadership in drug quality assurance to international efforts to improve the availability of safe, effective, and good-quality essential medicines. Through a cooperative agreement with USAID, USP's Global Assistance Initiatives program develops conferences and regional meetings on approaches to improving drug quality in collaboration with other organizations. At the country level, USP evaluates quality assurance systems and provides training to strengthen drug quality control labs and improve drug quality surveillance. In collaboration with WHO, USP also provides technical assistance in good manufacturing practices to targeted manufacturers.

Fellowships and Internships— USP offers a number of one-year fellowships to doctoral and postdoctoral candidates. A selection committee composed of USP Council of Experts and Expert Committee members and USP scientists evaluates the candidates. Six awards for standards-related studies were made for the period of July 1, 2005, through June 30, 2006. The purpose of the USP Fellowships is to promote postgraduate research in areas related to compendial standards.