Development of a New USP General Information Chapter: Verification of Compendial Procedures

Mar 02, 2006
Volume 30, Issue 3

Calibration, validation, and traceability are central components of metrology (1–3). The process of validating a new analytical procedure for compendial usage is addressed in US Pharmacopeia (USP) General Chapter ‹1225› "Validation of Compendial Procedures"* (4).

Even though a USP procedure is fully validated, one may not have assurance that the procedure is suitable for use with a specific ingredient or product, in a specific laboratory, with specific laboratory personnel, equipment, and reagents. The latter falls within the area termed verification, whereby analysts demonstrate that a validated procedure to be used for the first time with a particular product will yield acceptable results using a given laboratory's equipment, personnel, and reagents. Therefore, the purpose of the proposed General Chapter ‹1226› "Verification of Compendial Procedures" (5) is to provide guidance about the verification process.

USP developed this chapter in response to industry's requests to provide instructions for verifying compendial procedures. The authors note that verification is not mandatory unless an enforcing body adopts it by reference, it is referenced in a specific USP monograph, or it is adopted by a specific manufacturer in standard operating procedures subject to current good manufacturing practices (CGMPs) regulations (see also General Chapters, USP General Notices).

A compendial procedure is considered validated if it is published as official text in USP–National Formulary (NF), in a supplement, or as an Interim Revision Announcement in Pharmacopeial Forum (PF). Therefore, users of such procedures are not required to perform validation studies. But, they must demonstrate that the use of the official procedure is suitable given the actual conditions of use. This requirement is established by the US Food and Drug Administration's CGMPs, which state "The suitability of all testing methods used shall be verified under actual conditions of use" (6).

The suitability of a compendial procedure may be an issue for an article under test for several reasons (e.g., different impurity profiles from different routes of synthesis, composition of formulations, or interference from excipients). General Chapters already exist in the USP on the general topic. For example, various General Chapters for microbiological testing describe approaches that will ensure the article to be tested is suitable for use with the validated procedure. Similarly, many USP monographs have sections devoted to establishing the suitability of chromatographic systems.

If multiple laboratories are expected to use the compendial procedure with essentially the same conditions of actual usage, then one laboratory may perform the verification. With appropriate verification of adequate robustness, other locations may use the verified procedure. Some factors that must be considered when ascertaining usage conditions are:

  • article to be tested;
  • laboratories to be used;
  • equipment to be used;
  • personnel;
  • reagents.

Verification process

It is assumed that personnel involved in the verification process possess appropriate experience, knowledge, and training to execute a verification properly. A critical step in the verification process is the preparation of a document describing:

  • procedures to be verified;
  • number and identity of lots or batches of articles that will be used (note that the verification may need to be repeated for different types of articles);
  • analytical performance characteristics to be evaluated, along with a specification of the acceptable range of results expressed in terms of acceptable accuracy, precision, or linearity parameters;
  • justification of any deviations from the recommendations in General Chapter ‹1226›.

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