求助：USP40通则<1224>、<1225>、<1226>？:1226? VERIFICATION OF COMPENDIAL PROCEDURES The intent of this general information 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 test chapters Antimicrobial Effectiveness Testing ?51?, Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests ?61?, Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms ?62?, Sterility Tests ?71?, and in general information chapter Validation of Microbial Recovery from Pharmacopeial Articles ?1227?. VERIFICATION PROCESS The verification process for compendial test procedures is the assessment of whether the procedure can be used for its intended purpose, under the actual conditions of use for a specified drug substance and/or drug product matrix. 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 a procedure 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 of the particular procedure need to be evaluated. The process of assessing the suitability of a compendial analytical test procedure under the conditions of actual use may or may not require actual laboratory performance of each analytical performance characteristic. 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. Verification should assess whether the compendial procedure is suitable for the drug substance and/or the drug product matrix, taking into account the drug substance's synthetic route, the method of manufacture for the drug product, or both, if applicable. Verification should include an assessment of elements such as the effect of the matrix on the recovery of impurities and drug substances from the drug product matrix, as well as the suitability of chromatographic conditions and column, the appropriateness of detector signal response, etc. 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 procedure). 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 affect the recovery of the drug substance from the matrix. In these cases, a more thorough assessment of the matrix effects may be required to demonstrate suitability of the procedure 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 procedure 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 determinations 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. Director (301) 816-8319 (GCCA2015) General Chapters-Chemical Analysis 2015 USP40–NF35 Page 1786 Previously Appeared In: Pharmacopeial Forum: Volume No 查看更多
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