非无菌半固体制剂的放大和批准后辅料变更28.09KB.docx

III. COMPONENTS AND COMPOSITION组分和成分的变更This section of the guidance focuses on changes in excipients in the drug product. Qualitative changes in excipients should include only those excipients which are present in approved drug products for the specific route of administration. Quantitative changes in excipients should not exceed the amount previously approved in products with the same specific route of administration.2 The chronology of changes in components and composition should be provided. Changes in components or composition that have the effect of adding a new excipient or deleting an existing excipient are defined as level 3 changes (see section III.C below), except as described below. These changes generally result in the need to change the labeling.指南的本部分集中讲述了药品辅料的变更。辅料的性质变更应该只包含那些用于已批准的药物的特定给药途径。辅料的量变应该不超过同样给药途径的已批准量。组分和成分的变更需要提供时间表。组分和成分的变更涉及到新增辅料或是删除辅料时，归类为三级变更（见C部分），下述情况除外。这些变更通常会导致标签需要变更。Compositional changes in preservatives are considered separately and are not included as part of the total additive effect under sections III.A, B and C.防腐剂的组分变更单独考虑，不作为本部分A、B、C中的累加效应部分考虑。Level 1 Change一级变更Definition of Level级别定义Level 1 changes are those that are unlikely to have any detectable impact on formulation quality and performance.一级变更指的是那些不太可能对剂型的质量和功效有可检测的影响的变更。Examples:例如：Deletion or partial deletion of an ingredient intended to affect the color, fragrance, or flavor of the drug product.删除或部分删除辅料，这个辅料会影响药品的颜色、香味或口味。Any change in an excipient up to 5% of approved amount of that excipient. The total additive effect of all excipient changes should not be more than 5%. Changes in the composition should be based on the approved target composition and not on previous level 1 changes in the composition. A change in diluent (q.s. excipient) due to component and composition changes in excipient may be made and is excluded from the 5% change limit.任何辅料的变更量不超过已批准的辅料量的5%。所有辅料变更的总累加效应应不超过5%。成分的变更应该基于已批准的目标成分，并且不是基于前面的成分的一级变更。辅料中的组分和成分的变更可能导致的溶媒变更（定量辅料），这种变更不包含在5%变更限度中。