缓控释口服固体制剂放大和批准后的辅料变更指南试编.docxVIP

III. COMPONENTS AND COMPOSITION — NONRELEASE CONTROLLING EXCIPIENT组分和成分--非释放控制辅料This section of the guidance focuses on changes in nonrelease controlling excipients in the drug product. For modified release solid oral dosage forms, consideration should be given as to whether the excipient is critical or not critical to drug release. The sponsor should provide appropriate justifications for claiming any excipient(s) as a nonrelease controlling excipient in the formulation of the modified release solid oral dosage form. The functionality of each excipient should be identified. Changes in the amount of the drug substance are not addressed by this guidance. Changes in components or composition that have the effect of adding a new excipient or deleting an excipient are defined at level 3 (defined below), except as described below in Section III.A.1.a. Waiver of bioequivalence testing for a change in composition which involves only a different color, flavor or preservative may be permissible as described in 21 CFR 320.22(d)(4).本指南这部分主要针对药品非释放控制辅料的变更。对于缓控释固体口服制剂，应该对辅料是否为药物释放的关键辅料或非关键辅料进行考虑。发起人如果判定任何辅料为缓控释固体口服制剂中的非释放控制辅料，应该提供相应的理由。应该对每种辅料的功能进行识别。本指南未对药品中原料药量的变更进行规定。对组分或成分的变更中涉及到新增或删除辅料时，归类为3级变更，第III.A.1.a中的情况除外。成分的变更如果只涉及到变更颜色、口味或防腐剂，按照21 CFR 320.22(d)(4)的规定可能允许豁免生物等效性测试。A. Level 1 Change一级变更1. 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a. Deletion or partial deletion of an ingredient intended to affect the color or flavor of the drug product; or change in the ingredient of the printing ink to another approved ingredient.删除或部分删除组分，这个组分会影响药品的颜色或口味；或者将印刷用油墨成分变更为另一种已批准成分。b. Changes in nonrelease controlling excipients, expressed as percentage (w/w) of total formulation, less than or equal to the following percent ranges:非释放控制辅料的变更，以总配方的百分比表示，小于等于以下百分比范围：Nonrelease Controlling Excipient非释放控制辅料Percent Excipient (w/w)Out Of Total Target Dosage For