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1226 VERIFICATION OF COMPENDIAL PROCEDURES
The intent of this chapter is to provide general information on the verification of compendial procedures
that are being performed for the first time to yield acceptable results utilizing the personnel, equipment,
and reagents available. This chapter is not intended for retroactive application to already successfully
established laboratory procedures. The chapter Validation of Compendial Procedures 1225 provides
general information on characteristics that should be considered for various test categories and on the
documentation that should accompany analytical procedures submitted for inclusion in USP–NF.
Verification consists of assessing selected analytical performance characteristics, such as those that
are described in chapter 1225 , to generate appropriate, relevant data rather than repeating the
validation process.
Users of compendial analytical procedures are not required to validate these procedures when first
used in their laboratories, but documented evidence of suitability should be established under actual
conditions of use. In the United States, this requirement is established in 21 CFR 211.194(a)(2) of the
current Good Manufacturing Practice regulations, which states that the “suitability of all testing methods
used shall be verified under actual conditions of use.”
Verification of microbiological procedures is not covered in this chapter because it is covered in USP
general chapters Antimicrobial Effectiveness 51 , Microbiological Examination of Nonsterile Products:
Microbial Enumeration Tests 61 , Microbiological Examination of Nonsterile Products: Tests for
Specified Microorganisms 62 , Sterility Tests 71 , and Validation of Microbial Recovery from
Pharmacopeial Articles 1227 .
VERIFICATION PROCESS
Users should have the appropriate experience, knowledge, and training to understand and be able to
perform the compendial procedures as written. Verification should be conducted by the user such that
the results will provide confidence that the compendial procedure will perform suitably as intended.
If the verification of the compendial procedure is not successful, and assistance from USP staff has not
resolved the problem, it may be concluded that the procedure may not be suitable for use with the
article being tested in that laboratory. It may then be necessary to develop and validate an alternate
procedure as allowed in the General Notices. The alternate procedure may be submitted to USP, along
with the appropriate data, to support a proposal for inclusion or replacement of the current compendial
procedure.
VERIFICATION REQUIREMENTS
Verification requirements should be based on an assessment of the complexity of both the procedure
and the material to which the procedure is applied. Although complete revalidation of a compendial
method is not required to verify the suitability of the method under actual conditions of use, some of the
analytical performance characteristics listed in chapter 1225 , Table 2, may be used for the
verification process. Only those characteristics that are considered to be appropriate for the verification
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of the particular method need to be evaluated. The degree and extent of the verification process may
depend on the level of training and experience of the user, on the type of procedure and its associated
equipment or instrumentation, on the specific procedural steps, and on which article(s) are being tested.
As an example, an assessment of specificity is a key parameter in verifying that a compendial
procedure is suitable for use in assaying drug substances and drug products. For instance, acceptable
specificity for a chromatographic method may be verified by conformance with system suitability
resolution requirements (if specified in the method). However, drug substances from different suppliers
may have different impurity profiles that are not addressed by the compendial test procedure. Similarly,
the excipients in a drug product can vary widely among manufacturers and may have the potential to
directly interfere with the procedure or cause the formation of impurities that are not addressed by the
compendial procedure. In addition, drug products containing different excipients, antioxidants, buffers,
or container extractives, may potentially interfere with the compendial procedure. In these cases, a
more thorough assessment of specificity may be required to demonstrate suitability of the method for
the particular drug substance or product. Other analytical performance characteristics such as an
assessment of the limit of detection or quantitation and precision for impurities procedures may be
useful to demonstrate the suitability of the compendial method under actual conditions of use.
Verification is not required for basic compendial test procedures that are routinely performed unless
there is an indication that the compendial procedure is not appropriate for the article under test.
Examples of basic compendial procedures include, but are not limited to, loss on drying, residue on
ignition, various wet chemical procedures such as acid value, and simple instrumental methods such as
pH measurements. However, for the application of already established routine procedures to
compendial articles tested for the first time, it is recommended that consideration be given to any new or
different sample handling or solution preparation requirements.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
General Chapter Horacio N. Pappa, Ph.D. (GC05) General Chapters 05
Senior Scientist and Latin American Liaison
1-301-816-8319
USP32–NF27 Page 736
Pharmacopeial Forum: Volume No. 32(4) Page 1232
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