Chemistry Reference
In-Depth Information
Chapter 5 discusses this subject in more detail. But once a change has been made to
a method, an analyst can be faced with a number of situations:
1. Implement it as an existing standard method (USP, AOAC, or method in an
approved NDA or ANDA).
2. Implement it as an existing standard method with adjustments.
3. Implement it as an existing standard method with modifications or changes.
9.4 Implement An exIstIng stAndArd metHod
To implement an existing standard method, or to determine the suitability of the
method under actual conditions of use, verification is necessary to confirm that the
method works for a particular drug substance, excipients, or dosage form by
veri-
fying
a subset of validation characteristics per USP Chapter 1226, Verification of
Compendial Procedures, rather than completing a full validation [9]. The USP says
the purpose of this new general information chapter is to provide guidelines for veri-
fying the suitability of a compendial procedure under conditions of actual use. USP
Chapter 1226 summarizes what is necessary to confirm that the compendial proce-
dure works for a particular drug substance, excipients, or dosage form by verifying
a subset of validation characteristics, rather than completing a full validation. It is
considered an extension of Chapter 1225, and both chapters use similar terminology.
The intent of Chapter 1226 is to provide guidance on how to verify that a compen-
dial procedure that is being used for the first time will yield acceptable results uti-
lizing the laboratories' personnel, equipment, and reagents. Verification consists of
assessing selected analytical performance characteristics described in Chapter 1225
to generate appropriate relevant data, as opposed to repeating the entire validation
process. In draft versions, tables were included in Chapter 1226 outlining specific
recommended validation performance characteristics to verify a method for both
drug products and drug substances. However, the current version of Chapter 1226
provides only general recommendations.
9.4.1 v
erIfIcAtIon
Verification
is a recent term that refers to the suitability of a compendial procedure under
actual conditions of use. The International Organization for Standardization (ISO) puts
it this way: validation is confirmation, through the provision of objective evidence that
the requirements for
a specific intended use or application
have been fulfilled [10].
Verification is confirmation, through the provision of objective evidence that
specified
requirements have been fulfilled [11]. Put simply, compendial methods are verified, and
noncompendial or alternative analytical procedures are validated.
USP methods have always been assumed to be validated, but not knowing what
may have passed for validation when the method was submitted often leads analysts
down a path of partial- or re-validation, and Chapter 1225 does not provide any
guidance on how to verify procedures in the absence of a full validation protocol.
Verification is not required for basic compendial test procedures unless there is an
indication that the compendial procedure is not appropriate for the sample or matrix
