【正文】 urity 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”。 a change to a pharmaceutical excipient in a formulation may lead to changes to drug product specifications。 Type II, moderate changes, for which studies should be performed to demonstrate that the changes have no effect on the safety, effectiveness and quality controllability of the affected product 。 Type III, major changes that need a series of studies to demonstrate that the changes have no negative impact on the safety, efficacy and quality controllability of the affected product. The category of change types has taken into consideration the relevant regulation for supplemental application in of the current Drug Registration and Regulation (DRR) as well as relevant technical requirements of other countries in order to help the manufacturers to perform targeted change studies, summarize the study results into supporting information and make supplemental application to the regulatory agencies. 2 The changes referred to in this guideline are post approval changes aiming at marketed chemical drug products. Therefore, changes and change studies should be based on the studies and cumulative data in the past from the drug registration stage and actual manufacturing processes. The more systematic and thorough the research work in registration phase was and the more sufficient the data were accumulated from the manufacturing processes, the more helpful it would be for the postapproval change study. For specific requirements in this guideline, please refer to the technical guidelines for chemical drug research and development or other relevant technical guidelines previously issued. If there are other scientific investigation results with sufficient evidence available to demonstrate that the changes have no negative impact on the drug’ s safety, efficacy and quality controllability, it is unnecessary to perform the change studies by following this guideline. II. Basic principles for the studies in support of postapproval changes to chemical drug products The studies for post approval changes (or changes) referred in this guideline are those performed to support changes to chemical drug products that have been approved for marketing. Research and development work in the studies should generally follow the principles below: (1) Pharmaceutical manufacturers should drive the change studies and selfassessment of the study results. Based on the needs in manufacturing, etc., pharmaceutical manufacturers propose changes and perform relevant studies. Pharmaceutical manufacturers should have a prehensive and accurate understanding of the research amp。 or may result in changing packaging materials at the same time. In this guideline, changes paralleled to or consequential to another change are called Related Changes With respect to Related Changes, studies can be performed according to the guiding principles for various types of changes in this guideline. Because these changes may affect the product’ s safety, efficacy and quality controllability to different extents, ., related changes may be classified to different change types in this guideline, and studies may be carried out according to the respective technical requirements。 (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。 while making the change to the excipient, there is a need to add an HPLC test in the drug product specifications, and the latter change falls into Type I change for changing drug product registration specifications in this guideline. For the aboveme