Inside USP: Revising USP General Notices

The United States Pharmacopeia (USP) is in the process of revising the General Notices of United States Pharmacopeia (USP) and National Formulary (NF) and the General Provisions and Requirements of Food Chemicals Codex (FCC). These documents are key resources for users of USP–NF and FCC.

Since the third revision of USP (i.e., USP III, 1850) a Preliminary Notices (now the General Notices) section has assisted practitioners by defining certain terms and procedures that are used throughout the compendia.

For those who are not familiar with FCC, a brief background note is in order. FCC is a compendium of internationally recognized standards for purity and identity of food-grade substances and has been published by the Institute of Medicine (IOM) since 1966. FCC allows manufacturers of food, food chemicals, and food ingredients to comply with standards that have been created and vetted by a highly rigorous and transparent scientific process. Many pharmaceutical manufacturing processes were adapted from the food processing industry (e.g., tablet coating), and both industries share many ingredients (excipients).

The processes of revising USP–NF and FCC both rely on volunteer scientific experts whose work is open to public review and comment. USP acquired FCC from IOM in August 2006 with the goal of providing full support for the continuing revision and update of the compendium. Biennial revisions to the fifth edition of FCC are underway, and publication of the sixth edition is scheduled for February 2008. Further information is available at the USP website (www.usp.org). USP has created a Food Additives Stakeholder Forum, which convened its first meeting on Feb. 23, 2007.

Rationale for revisions to the General Notices

Proposed changes to General Notices will:

• Make it clear that all compendia published by USP are covered by the General Notices, which is important because the General Notices contain terms essential for understanding all monographs

• Standardize language among the compendia to make it easier for users who refer to both NF and FCC

• Update the language, some of which dates to 1920 and periodically suffers from archaisms

• Add headings to aid navigation and to allow users to refer to specific sections of the General Notices—for example, draft section 6 could take the following form:

6. Terms and Definitions

• 6.1 Abbreviations

• 6.2 About

• 6.3 Alcohol Content

• 6.4 Atomic Weights

• 6.5 Blank Determinations

• 6.6 Concomitantly

• etc.

• The combination of headings and numbers will both facilitate and clarify references to the General Notices. Instead of citing page, column, and line number along with an extensive quotation, users will be able to cite section number and title

• Refocus the text on essential information by moving other material to the Mission and Preface or to a General Chapter

• Accommodate new USP initiatives: FCC, Pending Standards, and Standards for Articles Legally Marketed outside the United States (SALMOUS)

• Clarify circumstances under which alternative procedures should be submitted to USP for evaluation as potential supplemental or replacement procedures (cf. Validation of Compendial Procedures <1225>)

• Clarify the intended application of text to, for example, compounded preparations versus drug products and active pharmaceutical ingredients versus excipients.

Official versus authorized text. The proposed revision to the General Notices attempts to clarify the distinction between official and authorized text. In this proposal, official text appears in USP, NF, FCC, or SALMOUS. All other text would be authorized.

Currently, all General Chapters are official by virtue of their inclusion in USP–NF and are recognized in law as official compendia of the United States. USP–NF distinguishes between enforceable and informational General Chapters by means of chapter numbers: Chapters numbered below 1000 are intended to be enforceable by FDA, but chapters numbered above 1000 are intended by USP to be informational only.

USP is aware that this numerical distinction is not entirely adequate and causes confusion within industry and regulatory authorities. Inclusion of General Information Chapters in the official compendium may at times cause them to be given greater regulatory status than USP intended. In addition, the distinction is imperfect: some chapters with numbers above 1000 may be referenced in a monograph, which makes the General Chapters mandatory for those monographs.

The current draft revision of the General Notices clarifies the text that is official, and therefore enforceable, in a new way:

• USP, NF, FCC, and SALMOUS monographs all would be official

• The General Notices would remain official

• General Chapters and FCC General Tests and Assays that are included in USP, NF, or FCC would be official and therefore enforceable, whether the chapter number is above or below 1000. These would include every General Chapter that is referenced in an official USP, NF, FCC, or SALMOUS monograph. Other General Chapters also would be included, as determined by the relevant USP Expert Committees. General Chapters that remain official might include those that provide information that is necessary to perform compendial procedures and those that are anticipated to be referenced in a monograph in the near future.

• Some information that currently is published in USP–NF would be considered authorized text only and would no longer be official. This text is expected to move to a new volume (the Companion Volume) that would not be called USP–NF in order to clarify to regulatory authorities that these materials are not intended to be enforceable. Some USP General Chapters would move to the Companion Volume. These chapters would retain their chapter numbers. The Reference Tables section of USP, including the Description and Solubility Table, also would move to the Companion Volume as authorized text.

• Pending Standards would remain authorized text. Manufacturers are not permitted to claim conformance to a Pending Standards monograph.

• Other text, such as Information monographs, would remain authorized and would remain outside of USP–NF and FCC.

The General Notices revision process

An overview of the General Notices revision process is posted on USP's website at www.usp.org/USPNF/generalNoticeshtml. The page contains a link to the 21-page proposed revisions. The revisions page will remain live for a first round of comments until August 31, 2007, and constituents are invited to submit comments via email to GeneralNotices@usp.org or to:

Executive Secretariat

Attn: General Notices

US Pharmacopeia

12601 Twinbrook Pkwy

Rockville MD 20852-1790

Crosswalks. The General Notices page also provides a crosswalk document that shows current USP, NF, and FCC text side-by-side with the proposed revised text for easy comparison. The proposed revisions as they compare to the General Notices in USP 30, NF 25, and FCC 5th Edition are presented at USP's website.

Revision process. After the close of the initial comment period on Aug. 31, 2007, USP staff will review carefully all comments received and incorporate revisions as appropriate. Throughout the summer of 2007, USP Expert Committees also will review the draft, comment on proposals, and consider related changes that may be necessary, including changes to General Chapters.

USP anticipates that a second draft of the proposed General Notices will be available at the USP Annual Science Meeting, Sept. 25–28, 2007. USP anticipates publishing this second draft on the USP website for comment and in Pharmacopeial Forum 33(6) in November 2007. The comment period will close on Feb. 15, 2008.

USP anticipates presenting comments received on the second draft as well as staff members' proposed resolution of the issues raised in the comments to the Council of Experts Executive Committee in spring 2008 for their consideration and approval. The proposed revised General Notices will not be published in USP and NF as official before USP 32–NF 27 (November 2008) and will not be published as official in FCC before the Supplement to the 6th edition (February 2009).

Revising the General Notices is a timely and thoughtful activity that USP is undertaking at the urging of its volunteer community and constituents, whom we thank in advance for their participation.

Roger L. Williams, MD,* is executive vice-president and chief executive officer; Todd L. Cecil, PhD, is vice-president of Documentary Standards Division (DSD), Ruth K. Miller, JD, is counsel of Legal Department, Stefan Schuber, PhD, is director, scientific reports in DSD, all at the US Pharmacopeia, 12601 Twinbrook Parkway, Rockville, MD 20852-1790, tel. 301.816.8300, rlw@usp.org. Dr. Williams is also a member of Pharmaceutical Technology's editorial advisory board.

*To whom all correspondence should be addressed.

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