Composition of the USP Pharmacists Pharmacopeia

We will look in detail at selected portions of the Introductory Material, as follows.

INTRODUCTORY MATERIAL

CONTENT OF UNITED STATES PHARMACOPEIA-NATIONAL FORMULARY

USP-NF contains official substance (ingredient) and product monographs for official articles recognized in USP-NF.

(See General Notices 2.20 Official Articles)

USP-NF also includes monographs for compounded preparations. With few exceptions, such as articles covered by Global Health monographs, the intent is that all articles for which monographs are provided in USP-NF are legally marketed in the United States or are contained in legally marketed articles.

Global Health monographs are provided for articles that are not approved or legally marketed in the United States, but that have been approved by a stringent regulatory authority [as defined by the World Health Organization (WHO)] and are used for essential purposes in other parts of the world (see General Notices 3.10.40 Applicability of Global Health Monographs).

A USP-NF monograph for an official substance, product, or preparation may consist of various components, including the article's name; definition; packaging, storage, and other requirements; and a specification. General chapters provide frequently cited procedures, sometimes with acceptance criteria, in order to compile into one location repetitive information that is applicable to many monographs. See General Notices 3.10 Applicability of Standards for more information about standards contained in USP-NF monographs and general chapters.

The USP Admissions List section of the USP-NF indicates those new and revised monographs and general chapters as well as any omissions that were published on a specific delivery date.

Revisions to USP-NF - USP-NF is continuously revised by an exceptional process of public involvement and substantial interaction between USP and its stakeholders, both domestically and internationally. Revisions are presented in the USP-NF three times per year in November, February, and June. Accelerated Revisions [including Errata, Interim Revision Announcements (IRAs), and Revision Bulletins] are published periodically and with greater frequency.

Standard Revisions - USP's standard revision process calls for publication of a proposed revision in the PharmacopeialForum (PF) for a 90-day notice and comment period and, after the revision is approved by the relevant USP Expert Committee, publication in the USP-NF.

Accelerated Revisions - The Accelerated Revision process is used to make revisions to USP-NF official more quickly than through USP's Standard Revision process. Learn more about accelerated revisions and the criteria for and implementation thereof on the USP website (http://www.uspnf.com/official-text).

Modification of Compendial References - USP and its Expert Committees periodically deem it necessary to modify general chapter titles or similar text that may be referenced in other standards throughout the USP-NF. When this occurs, USP staff undertake a rigorous process for identifying and updating such references. These updates may occur through a routine revision, or, in cases in which an update appears to present no significant change in the affected standard, through a direct update of the reference in that standard without providing an opportunity for notice and comment. In all cases, USP will publish on its website a notice indicating the source change, any resulting references, and whether those references will be updated through a routine revision or a direct update.

Updating Chemical Information - Updates to the Chemical Information section at the beginning of monographs occur on an ongoing basis and are not identified with revision symbols. Chemical names and molecular weights are updated when a monograph undergoes revision to match the official source, United States Adopted Names (USAN). Chemical structures are updated on a continuous basis. Chemical names typically reflect the naming conventions at the time of the monograph development or revision. If the nomenclature rules of CAS or IUPAC are significantly changed, the chemical names can be revised or added to implement those rules. Molecular weights are derived from the chemical formula and are based on the table of atomic weights. Atomic weights are recommended by the IUPAC and reflect the isotopic composition of normal terrestrial material. When the IUPAC recommended values are changed, it is understood that the changes in molecular weights will be made in due course.

Graphical representation of the chemical compound structures is intended as a visual aid to help establish chemical identity and is understood to represent one of many possible ways to depict the molecule. Addition of a graphical representation or changes in such representation, that result in the same chemical information, e.g., a flipped chiral molecule or adding a molecule structure, may be introduced outside of the revision process. It is also understood that in the case of tautomerism, the molecule depicted may be one of the tautomers, but it is intended to represent all isomers in equilibrium. Stereogenic centers depicted with plain bonds imply mixtures of pertinent stereomers-enantiomer, diastereomers, epimers (anomers), etc. (see General Notices 3.10 Applicability of Standards).

Shading and Symbols - Shading is used to identify text that has been modified, added, or deleted since it was last published. Symbols identify the beginning and end of each revision or nonharmonized text.

Commentary - For revisions that are published for public review and comment in PF, the proposal may advance to official status or be republished in PF for further notice and comment. If comments are received, they are considered and incorporated as appropriate by the Expert Committee(s). In cases where proposals advance to official status without republication in PF, a summary of comments received and the appropriate Expert Committee's responses are published in the Commentary section of the USP website at the time the revision is published.

The Commentary is not part of the official text and is not intended to be enforceable by regulatory authorities. Rather, it explains the basis of the Expert Committee's response to public comments. If there is a difference between the contents of the Commentary and the official text, the official text prevails. In case of a dispute or question of interpretation, the language of the official text, alone and independent of the Commentary, shall prevail.

USP-NF Presentations - See General Notices 2.10 Official Text for more information about USP-NF product formats. The USP-NF is available online. USP 43-NF 38 (published November 1, 2019) was the last publication made available in print or on a flash drive.

USP-NF Translations - Translations of the USP-NF are available in Spanish, Russian, and Chinese. The Spanish translation is current; other translations are based on previous revisions of the USP-NF.

USP Reference Standards - The use of USP Reference Standards promotes uniform quality of drugs and supports reliability and consistency by those performing compliance testing and other users of USP-NF, including manufacturers, buyers, and regulatory authorities. USP Reference Standards are referenced in specific procedures in both monographs and general chapters. USP advances this material via careful characterization studies and collaborative testing, followed by review and approval of the compendial use of the reference material by Expert Committees of the Council of Experts. This program benefits from the widespread voluntary contribution of suitable materials and test data from pharmaceutical manufacturers. The USP Catalog, which lists the collection of USP Reference Standards, and more information about use and storage, can be accessed on USP's website ( https://www.usp.org/​reference-standards​/reference-standards-catalog).

USP GOVERNING, STANDARDS-SETTING, AND ADVISORY BODIES

USP's governing, standards-setting, and advisory bodies include the USP Convention, the Board of Trustees, the Council of Experts and its Expert Committees, Expert Panels, Subcommittees, Joint Standard-Setting Subcommittees, and staff. Additional volunteer bodies include Stakeholder Forums and Project Teams, which offer stakeholders the opportunity to contribute, through advice and recommendations, to the advancement of USP's standards and processes. Learn about the composition and work of the USP Convention, Board of Trustees, Expert Committees, and Expert Panels on the USP website (https://www.usp.org/about/convention-membership).

Learn more about Stakeholder Forums and Project Teams on the USP website (https://www.usp.org/get-involved/provide-input/stakeholder-forums). A listing of all current Voting Delegates of the USP Convention and members and Government Liaisons to the Council of Experts and its Expert Committees and Expert Panels is included in the People section.

Working with the Food and Drug Administration - USP works with the Secretary of the Department of Health and Human Services, and the principal agency in the Department for this work is the Food and Drug Administration (FDA). USP works in many ways with the agency, but the primary interaction is through the Government Liaison Program. The Government Liaison Program allows representatives of FDA and other government agencies to participate in Expert Committee and Expert Panel and related meetings, enabling interactions between government staff and Expert volunteer bodies. Staff in the FDA Centers who are responsible for review of compendial activities provide specific links and opportunities for exchange of comments. The Office of Policy for Pharmaceutical Quality in the Center for Drug Evaluation and Research provides a primary compendial point of contact between FDA and USP.

RULES AND PROCEDURES

Governing Documents - USP-NF standards are recognized widely because they are authoritative and science-based and are established by a transparent and credible process. See the Articles of Incorporation section in this book; the Bylaws (https://www.usp.org/about/convention-membership/bylaws), and the Rules and Procedures of the Council of Experts (https://www.usp.org/about/leadership/policies-rules). Collectively, these documents serve USP volunteers and staff as the governing principles for USP's standards-setting activities.

LEGAL RECOGNITION

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 (FD&C Act) defines the term "official compendium" as the official USP, the official NF, the official Homeopathic Pharmacopeia of the United States, or any supplement to them. USP-NF standards play a role in the adulteration and misbranding provisions of the FD&C Act, which apply as well to biologics, a subset of drugs, under the Public Health Service Act (see General Notices 2.30 Legal Recognition).

FDA requires that names for articles that are not official must be clearly distinguished and differentiated from any name recognized in an official compendium. Drugs with a name recognized in USP-NF also will be considered misbranded unless they meet compendial standards for packaging and labeling (see General Notices 3.10.10 Applicability of Standards to Drug Products, Drug Substances, and Excipients for more information).

Drugs - USP's goal is to have substance and drug product monographs in USP-NF for FDA-approved drugs in the United States, including chemical and biologic medicines, and their ingredients. USP also provides monographs in USP-NF for legally marketed therapeutic products not approved by FDA, e.g., pre-1938 drugs, over-the-counter (OTC) drugs marketed under FDA's OTC Monograph system, dietary supplements, and compounded preparations. The Global Health section of USP-NF contains monographs for articles that are not approved or legally marketed in the United States, but that have been approved by a stringent regulatory authority (as defined by WHO) and are used for essential purposes in other parts of the world. Conformance with a USP-NF monograph, if applicable, is required at all times in the life of an article from production to expiration.

Biologics - In the United States, biologics are considered to be a subset of drugs, whether they were approved by FDA under the FD&C Act [and received a new drug application (NDA)] or under the Public Health Service Act [PHS Act, where they receive a biologics license application (BLA)]. As of March 23, 2020, applications for biological products approved under the FD&C Act will be deemed to be licenses for the biological products under the PHS Act. All PHS Act biologics are subject to the applicable drug regulatory requirements of the FD&C Act, which means they are required to comply with the adulteration and misbranding provisions of the FD&C Act, including USP-NF compendial requirements, to the extent that such requirements apply to a particular biologic product. This is equally so for biologics approved under the long-standing PHS Act "351(a)" pathway, as well as the new "351(k)" pathway for biosimilars added by the 2010 healthcare reform legislation (Biologics Price Competition and Innovation Act, Title VII, Subtitle A of the Patient Protection and Affordable Care Act, Public Law 111-148).

Dietary Supplements - The Dietary Supplement Health and Education Act of 1994 amendments to the FD&C Act provide that a dietary supplement may be deemed a misbranded food if it is covered by the specifications of an official compendium (e.g., USP-NF), is represented as conforming to the specifications of an official compendium, and fails to so conform. This contrast with pharmaceutical products, wherein conformance to applicable compendial standards is mandatory, whether or not the product claims to conform.

Compounding - USP provides general chapters and monographs for compounded preparations, as well as monographs for bulk substances used in compounding. USP standards are recognized in various provisions of the FD&C Act and such provisions do not differentiate between manufactured and compounded medicines. Moreover, the FD&C Act and the 2013 Drug Quality and Security Act specifically reference USP standards for compounding. Learn more about compounding on the USP website (https://www.usp.org/compounding).

Medical Devices - Section 201(h) of the FD&C Act defines a device as an instrument, apparatus, similar article, or component thereof recognized in USP-NF. Section 502(e) of the FD&C Act 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 role in establishing compendial standards for medical devices as exists for drugs and biologics. Under authority granted by the Food and Drug Administration Modernization Act of 1997, the Center for Devices and Radiological Health recognizes national and international standards, including some USP tests and assays, for medical devices.

Nomenclature - For information on the nomenclature development process, the Nomenclature and Labeling Expert Committee, and USP's work with United States Adopted Names (USAN), see the USP website (https://www.usp.org/expert-committees/nomenclature-and-labeling-expert-committee-work-plan).

Chemical Names and CAS Registry Numbers - Chemical subtitles given in the monographs are CA Index Names used by CAS, a division of the American Chemical Society. CAS Registry Number(r) and CAS RN(r) are registered trademarks 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 for the purpose of the Collective Index (CI). The second subtitle, given in uninverted form, is a preferred IUPAC name (PIN) sanctioned and used by the International Union of Pure and Applied Chemistry (IUPAC). Preferred IUPAC names also are used by the WHO. Occasionally a third subtitle is supplied for historical reasons or when the synonym uses an alternative, but equivalent, naming convention. Monographs with chemical subtitles also generally carry CAS registry numbers. These bracketed numbers function independently of nomenclature as invariant numerical designators of unique, unambiguous chemical substances in the CAS Registry^SM, and thus are convenient and widely used.

HARMONIZATION ACTIVITIES

USP participates in several collaborative activities.

Next Week: We will continue looking at other important details of the USP Pharmacists Pharmacopeia.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

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