Identifying Official Text

1. What is the definition of “official text” in the USP–NF?

All text in the United States Pharmacopeia (USP) or National Formulary (NF) that has reached its official date is “official text.”

The Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321 et. seq.) defines “official compendium” to mean “the official United States Pharmacopeia, official Homoeopathic Pharmacopoeia of the United States, official National Formulary, or any supplement to any of them.”  21 U.S.C. 321(j). 

2. How do I know the status of a compendial standard, i.e., whether it has become “official”?

Routine revisions are published in the USP–NF Online and become official on the date indicated, usually six months after publication. Accelerated Revisions (Revision Bulletins, Interim Revision Announcements (IRAs), Errata, and Compendial Notice Reference Changes) supersede content in the USP–NF Online and become official on the date indicated. See this link for more information regarding USP’s Accelerated Revisions.
In practice, users can determine whether text has become “official” in the following ways:

  • In the USP–NF Online (http://www.uspnf.com): The presence of a green header bar and the terms, “CURRENTLY OFFICIAL” indicate that the standard you are viewing contains official text. Note: Compendial users have access to other text in the USP–NF Online. For example, text that is “NOT YET OFFICIAL” is provided to enable early adoption or preparation for implementation. See the official status tutorial at this link for more information on determining the status of text in the USP-NF Online.
  • In print and USB flash drive versions of the USP–NF: Generally speaking, official text may be found by reviewing the print or flash drive version of the “currently official” version of the USP–NF. However, official text published in Supplements supersedes that in the previously published print or USB flash drive versions of USP–NF. These versions also are superseded by Accelerated Revisions as described above. In order to ensure access to all currently official text, a user must check whether any Supplement revisions or Accelerated Revisions supersede the text available in the print and USP flash drive versions.
3. If there is a difference between the print or USB flash drive versions of the USP–NF and the USP–NF Online, which version should be considered official?

In the event of any disparity between the print or USB flash drive versions and the USP–NF Online, the USP–NF Online will apply. See General Notices 2.10.

4. If a hyperlink in the USP–NF Online directs users to incorrect/inconsistent content or generates an error message, what should be considered “official text” in that case?

In the event that a hyperlink is missing or malfunctioning (e.g., linking to an incorrect document/document section or generating an error message), it is the text being displayed – and not the incorrect content or the error message generated by the hyperlink – that constitutes the official text of the relevant compendium.

Standards in the USP–NF Online may contain hyperlinks that are intended to serve as a convenience for customers. These hyperlinks may direct users to other sections of the USP–NF, to the iStore, or to third-party/external websites. Although the visible text that overlays a hyperlink is “official text,” the hyperlink functionality itself is not.

In the following example:

image

The text, “Chromatography <621>, System Suitability” represents the official text of the USP–NF.

USP appreciates being made aware of missing or malfunctioning hyperlinks. To report these issues, please email us at uspnf-info@usp.org. USP will catalog identified issues with hyperlinks and address them as soon as practicable.  

5. If revision markup in the USP–NF is missing or contains errors, what should be considered “official text” in that case?

Although the verbiage that has been inserted or deleted is “official text,” the revision markup itself is not. Standards in the USP–NF contain revision markup that is intended to serve as a convenience for customers. These tags are intended to indicate insertions, deletions, revision vehicles, and associated official dates.

In the following example from the USP–NF:

image

The text, “If it is intended for use in animals, it is so labeled.” represents the official text of the USP–NF.  

“Official Text” and Compliance with USP-NF Standards

6. Does all “official text” state requirements with which compendial users must comply?

Not all official text states requirements with which compendial users must comply. Although all text of the USP–NF that has reached its official date is “official text,” some official text is intended to assist or guide compendial users or to serve informational purposes.
The following sections of the USP–NF contain informational official text intended to aid compendial users, but do not state requirements with which users must comply:

  • Admissions and Annotated Lists
  • Front Matter
    • Mission and Preface
    • People 
    • Members and Delegates of the United States Pharmacopeial Convention
    • Recognition of Monograph and Reference Material Donors
    • Articles of Incorporation
    • Notice and Warning
    • Six-Month Implementation Guideline
    • USP Governance
  • Reagents and Reference Tables
    • Reagents, Indicators, and Solutions
    • Reagent Specifications
    • Indicators and Indicator Test Papers
    • Solutions
    • Chromatographic Columns
    • Reference Tables
  • Auxiliary Information (viewable only in USP–NF Online)
  • General Chapters numbered between <1000> and <1999>
  • Chapter Charts
  • The header bar displayed in the USP–NF Online, which serves to indicate the current status of the compendial standard
  • Any pop-up text displayed in the USP–NF Online, which serves to call the user’s attention to specific circumstances related to the use of a particular standard or standards
7. What is the significance of the reagents specifications listed in the Reagents and Reference Tables section of the USP–NF?

The reagents provisions in the USP–NF describe the grade and purity of commercial material necessary to complete the procedure referencing the reagent. The reagents provisions by themselves do not state requirements with which compendial users must comply. Rather, it is the monographs and General Chapters that reference the reagents that state requirements. The addition of or revision to a reagent generally is completed by USP staff.

8. Is compliance with USP–NF monographs legally required?

USP–NF monographs state requirements and apply to any articles that are marketed in the United States that are intended or labeled for use as drugs or as ingredients in drugs. Compliance with the monograph is required regardless of whether the article is designated as “USP” or “NF” on the label.

  • For example, the monograph for Ibuprofen Tablets is applicable to all products labeled with the name Ibuprofen Tablets regardless if the designation “USP” or “NF” is used. The monograph for Ibuprofen Tablets applies to tablets dispensed by prescription or those that are available over-the-counter.

Enforcement of USP standards is the responsibility of FDA and other government authorities in the U.S. and elsewhere. USP has no role in enforcement.

9. How do General Chapters become applicable and compendially required with respect to specific articles?

A General Chapter numbered below 1000 (or above 2000, for dietary supplements) becomes applicable and compendially required (an “applicable General Chapter”) with respect to specific articles in the following ways:

  1. Where it is referenced in a monograph
  2. Where it is referenced in another applicable General Chapter numbered below 1000 (or above 2000, for dietary supplements)
  3. Where it is referenced in General Notices

For example:

  1. General Chapter <621> Chromatography is an applicable General Chapter because it is referenced in monographs for drug substances and drug products.
  2. General Chapter <661> Plastic Packaging Systems and Their Materials of Construction is an applicable General Chapter because it is referenced in General Chapter <659> Packaging and Storage Requirements  (which, in turn, is an applicable General Chapter because it is referenced in General Notices).
  3. General Chapter <795> Pharmaceutical Compounding – Nonsterile Preparations and <797> Pharmaceutical Compounding – Sterile Preparations are applicable General Chapters because they are referenced in General Notices.
10. Can a USP General Chapter numbered 1000 to 1999 ever be made applicable and compendially required with respect to specific articles?

From a compendial standpoint, General Chapters numbered 1000 to 1999 are for informational purposes only. They contain no mandatory tests, assays, or other requirements applicable to any official article, regardless of citation in a monograph, a General Chapter numbered below 1000, or General Notices.

  • For example, General Chapter <1163> Quality Assurance in Pharmaceutical Compounding is not compendially required (although it is referenced in <795>). General Chapter <1163> is only for informational purposes because it is numbered above 1000.

Although it is possible for FDA or another government authority in the U.S. or elsewhere to require the use of a USP General Chapter numbered 1000 to 1999, the authority in question would need to make this requirement expressly applicable under law, regulation, or another appropriate vehicle that prescribes enforceable requirements.

11. Can a USP General Chapter numbered below 1000 ever be applicable and required from a compendial perspective if it is not referenced in a monograph, another applicable General Chapter, or General Notices?

From a compendial standpoint, a USP General Chapter numbered below 1000 is not applicable or compendially required if it is not referenced in a monograph, another applicable General Chapter, or General Notices.

Absent one of the references described above, it is nevertheless possible that FDA or another government authority in the U.S. or elsewhere may require the use of any USP General Chapter numbered below 1000. However, the authority in question would need to make this requirement expressly applicable under law, regulation, or another appropriate vehicle that prescribes enforceable requirements.

12. How do I know which sections of an applicable General Chapter specify requirements versus recommendations?

USP is aware that the language used in General Chapters has important legal and regulatory implications for stakeholders. Generally speaking, requirements in a General Chapter are conveyed in the following ways:

  • Use of the terms, “must” or “shall”.
  • Use of language that indicates how a procedure or action is done, e.g., “This test or an equivalent test is performed at least annually under conditions that closely simulate the most challenging or stressful conditions encountered during compounding.”
  • Use of language in the form of a command or directive, e.g., “Perform antiseptic hand cleansing.”

The words “should” and “may” are very different from “must” or “shall.” These two sets of terms are not interchangeable. “Should” and “may” indicate recommendations, whereas “must” and “shall” indicate obligations or requirements.