【正文】 anges 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 productsThe 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。amp。 development work, manufacturing and properties of their products. They should clearly understand the reason for the proposed change, extent of the change to the products and the impact of the change to the product when a change is being consideration. Hence, changes to a chemical drug product should be driven by pharmaceutical manufacturers.Pharmaceutical manufacturers should carry out a prehensive study for the product’s quality, stability and biological properties before and after a change. Pharmaceutical manufacturers should also carefully analyze the study results and evaluate the impact of the proposed change to product quality, ., whether the product’s quality is the same and therapeutic effect is equivalent before and after the change. Selfassessment for the study results is specifically emphasized.3(2) A plete and prehensive evaluation for the impact of change to the safety, efficacy and quality controllability of the drug product.Because drug research amp。amp。 development work and manufacturing processes are closely related, changes to manufacturing process, excipient with pharmaceutical application in the drug product formulation or quality standards etc., could affect the overall safety, efficiency and quality controllability of the drug product. If invitro studies can not accurately determine how a change affects the product, it is necessary to perform more indepth studies, prehensive evaluation for the impact of the change to the safety, efficacy and quality controllability of the drug product. This is also the starting point for the change study.Generally, a change study should take into consideration of the following aspects:1. Evaluation of Impact of Changes on Drug ProductsWhen a change was made to a product, a study should be carried out to evaluate and assess the impact of the change to the safety, efficacy and quality controllability of the drug product, including evaluation of changes to product chemistry, physics, microbiology, biology, biological equivalence, and/or stability. The study should be designed based upon a prehensive consideration about the specifics and type of the change, drug substance and /or dosage forms, and degree of impact of the change to the drug product, etc. For example, to evaluate any change of impurities in a drug product prior to and post a change, it is appropriate to first select or establish a suitable chromatographic method, and then perform a parative analysis of the impurity profiles (types and amount of impurities) prior to and post a change. If new impurities appear after a change, or if levels of existing impurities exceed the established limits, then it is necessary to determine whether the impurity levels are acceptable or not with rationales according to the Appendix 1 or 2 of “Technical Guideline for Study of Impurities in Chemical Drug Products”； If it is not acceptable, then a decision tree should be referenced to decide the subsequent step of work including consideration for carrying out any needed toxicology studies.In addition to the studies suggested under each change type in this guideline, it is also necessary to perform other selected important studies by taking into consideration of the characteristics and specifics of the change. For example, for some changes to a tablet manufacturing process, besides paring dissolution/release performances, it is also necessary to assess if there are any changes to other physical parameters.2. Evaluation of Sameness or Equivalence prior to and post Change4Strictly speaking, it is unnecessary for a product to remain pletely identical before and after a change, however, the product must keep the sameness and equivalence, namely, the product must have the same quality and clinical equivalence.Based on the study and qualification about the chemistry, physics, microbiology, biology, biology equivalence and stability of a product, prehensive analysis should be carried out to evaluate how a change would impact drug safety, efficacy and quality controllability. In general, by paring and analyzing of the results before and after a change, it can be determined whether the results pre and post change are equivalent. The parison studies include dissolution and release as well as a thorough parative analysis of a property, such as drug product stability, etc.In some cases, however, the products are unable to retain the same equality or equivalence after the change, ., the change may have affected the product safety, efficacy and quality controllability. If a pharmaceutical manufacturer still wishes to implement the change, it must prove that the change will not negatively impact the product quality through a series of pharmacological and biological studies. For example, if the studies found that certain manufacturing process changes could result in new degradation products. However, further study shows that the degradation products will not raise concerns about the drug safety. Therefore, this change still can be implemented.3. Considerations about the samples used for studiesIf a change occurs at th