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【正文】 ideal scenario. due to various reasons, . the lack of suitable test methods for the impurities of intermediates, the lack of impurity data from the original process with which can be pared, or the difficulty in isolating intermediates for study, etc. Under these circumstances, the consistency of impurity profile may be demonstrated by testing the impurities in the drug substance. Therefore, the equivalency of the pre and postchange impurity profile can be demonstrated by paring the impurity profiles of either the intermediates or the drug substances. However, when it is not possible to isolate intermediate from a multistep reaction mixture, it is not possible to prove that the pre and postchange impurity profile is consistent by studying the impurities of intermediates. The impurity test method to be used should be able to effectively separate and test both existing and new impurities. For a newlyestablished impurity test method, a detailed method evaluation should be performed. A parison of the pre and postchange impurity profiles should be carried out in the same manner. In general, at least three consecutive postchange batches should be tested and pared with at least three prechange batches. The pre and postchange impurity profiles can be considered consistent if the results meet the following requirements: (1). no new impurity at more than % are detected in the postchange intermediates, or new impurities in the drug substance are within the specification limits prescribed by “Technical Guideline for Study of Impurities in Chemical Drugs”。 (2). levels of existing impurities and total impurities are within the specification limits. If there are no specifications, their levels should be within the ranges of test results from multiple batches by the original manufacturing process。 (3). Residual levels of new solvents used meet the requirements of “Technical Guideline for Study of Residual Organic Solvents in Chemical Drugs”； (4). Levels of new inanic impurities meet the requirements of “Technical Guideline for Study of Impurities in Chemical Drugs”. 2. Physical Properties 8 In general, most synthetic processes involve dissolving a crude drug substance in a suitable solvent, isolating and purifying it through recrystallization or precipitation. This step is closely related to the physical properties of the drug substance. Normally the manufacturing process changes prior to the final reaction intermediates do not affect the physical properties of the drug substance. However, certain changes, ., changes leading to significant increase of existing impurities in the solution of crude drug substance or formation of new impurities, may affect the physical properties such as the crystal form of the drug substance. Therefore, if the physical properties of the drug substance directly affect the dosage form properties, and if the impurity profiles of the pre and postchange before the last reaction intermediates are not consistent, it is necessary to study the consistency of the physical properties of drug substances manufactured by the pre and post process changes. Drug substance particle size and polymorphic form are the primary physical properties that may affect the dosage form properties. Polymorphic form includes hydrates, solvates and amorphous solids. In certain cases, other physical properties, such as bulk density, may also need to be considered in the study. In general, at least three consecutive postchange batches should be tested, and should be pared with at least three prechange batches. If the results show that the polymorphic form and particle size meet the requirements on the specifications, or if not specified, the test results are within the ranges of test results from multiple batches by the original manufacturing process, the physical properties of the drug substances manufactured pre and post process change is considered the same. If test results show that the impurity profiles and physical properties of a reaction product (or drug substance) manufactured pre and post the process change are consistent, the quality of the drug substance remains consistent. If studies show that the quality of the pre and postchange drug substance is not consistent, and process changes affect the drug product quality to some degree, more indepth and prehensive studies should be performed from the safety and efficacy perspectives. For example, if the types or levels of impurities exceed the original specifications, or new impurities appear, the impurities should be studied according to “Technical Guideline for Study of Impurities in Chemical Drugs”. (2) Type I Changes 1. Changes to the source of reagents and starting materials In general, changes to the source of reagents and starting materials in a synth