发布时间 : 星期一 文章翻译（SUPAC-IR指导原则：速释口服固体制剂：放大生产和批准后变更）更新完毕开始阅读8b054710aaea998fcd220e0e
报中提供的一批长期稳定性试验数据。
Significant body of information not available: （未积累大量信息的情况）
Up to three batches with three months accelerated stability data reported in supplement; one batch on long-term stability data reported in annual report.
在补充申请资料中应提供3批3个月的加速稳定性试验数据；在年报中提供一批的长期稳定性试验数据。
b. Dissolution Documentation 溶出研究资料
Case B dissolution profile as described in Section III.B.2.b. 在章节III.B.2.b中规定的情况B的溶出曲线。
c. In Vivo Bioequivalence Documentation 体内生物等效性试验资料
Full bioequivalence study. The bioequivalence study may be waived with an acceptable in vivo/in vitro correlation has been verified.
完整的生物等效性研究资料。当该药品被证明具有可接受的体内外相关性时，可以免除生物等效性研究。
3. Filing Documentation 归档文件
Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).
此前批准的补充申请文件（所有信息，包括加速稳定性试验数据）；年报（长期稳定性试验数据）
IV. SITE CHANGES 生产地点变更
Site changes consist of changes in location of the site of manufacture for both company-owned and contract manufacturing facilities and do not include any scale-up changes, changes in manufacturing (including process and/or equipment), or changes in components or composition. Scale-up is addressed in Section V of this guidance. New manufacturing locations should have a satisfactory current Good Manufacturing Practice (CGMP) inspection.
地点的变更包括企业自有的和合同制造企业的生产地点变更，不包括生产规模放大的变更，生产的变更（包括工艺和/或设备），或者药品成分或组成的变更。对于生产规模放大的变更的规定见本指导原则的章节V。新的生产地点应通过CGMP认证。
A. Level 1 Changes 1类变更
1. Definition of Level 定义
Level 1 changes consist of site changes within a single facility where the same equipment, standard operating procedures (SOP's), environmental conditions (e.g., temperature and humidity) and controls, and personnel common to both manufacturing sites are used, and where no changes are made to the manufacturing batch records, except for administrative information and the location of the facility. Common is defined as employees already working on the campus who have suitable experience with the manufacturing process
1类变更是指同一企业内的生产地点改变，但变更前后的生产设备、标准操作规范（SOP’s）、环境条件（比如温度和湿度）、质量控制和人员素质等方面完全一致，批记录中除管理信息和生产地点外，其它内容不得改变。相同的人员素质是指已在该生产地点工作一段时间，且对生产工艺具备足够经验的人员。
2. Test Documentation 试验资料
a. Chemistry Documentation 化学资料
None beyond application/compendial release requirements.
申报资料/药典要求的资料，不需要其它资料。 b. Dissolution Documentation 溶出研究资料
None beyond application/compendial release requirements. 申报资料/药典要求的资料，不需要其它资料
c. In Vivo Bioequivalence Documentation 体内生物等效性资料
None. 不需要
3. Filing Documentation 归档文件
Annual report. 年报
B. Level 2 Changes 2类变更
1. Definition of Level 定义
Level 2 changes consist of site changes within a contiguous campus, or between facilities in adjacent city blocks, where the same equipment, SOP's, environmental conditions (e.g., temperature and humidity) and controls, and personnel common to both manufacturing sites are used, and where no changes are made to the manufacturing batch records, except for administrative information and the location of the facility. 2类变更是指变更前后的生产地点位于毗邻区域，或在毗邻的街区，且变更前后的生产设备，标准操作规范，环境条件（比如温度和湿度）、质量控制和人员素质应完全一致，生产记录中除了管理信息和生产地点外，其它内容不得改变。 2. Test Documentation 试验资料
a. Chemistry Documentation 化学资料
Location of new site and updated batch records. None beyond application/compendial release requirements.
One batch on long-term stability data reported in annual report.
生产地点的变更声明和最新的批记录。申报资料/药典要求的资料，不需要其它资料。
在年报中提供一批的长期稳定性试验数据。 b. Dissolution Documentation 溶出研究资料
None beyond application/compendial release requirements.
申报资料/药典要求的资料，不需要其它资料。
c. In Vivo Bioequivalence Documentation 体内生物等效性资料
None. 不需要
3. Filing Documentation 归档文件
Changes being effected supplement; annual report (long- term stability test data). 实施变更的补充申请资料；年报（长期稳定性试验数据）。
C. Level 3 Changes 3类变更
1. Definition of Level 定义
Level 3 changes consist of a change in manufacturing site to a different campus. A different campus is defined as one that is not on the same original contiguous site or where the facilities are not in adjacent city blocks. To qualify as a Level 3 change, the same equipment, SOP's, environmental conditions, and controls should be used in the
manufacturing process at the new site, and no changes may be made to the manufacturing batch records except for administrative information, location and language translation, where needed.
3类变更是指变更前后的生产地点位于不同的区域。不同区域是指位于变更前生产地点的非毗连的地点或非毗邻的街区。达到3类变更的要求，变更前后的生产设备、标准操作规范、环境条件和质量控制应一致，批记录中除了管理信息、生产地点和翻译的语言（如果需要的话）外，其它内容不得改变。 2. Test Documentation 试验资料
a. Chemistry Documentation 化学资料
Location of new site and updated batch records. Application/compendial release requirements. 生产地点变更声明和最新的批记录。 申报资料/药典要求的资料。 Stability: 稳定性研究资料
Significant body of data available: （已积累大量信息的情况）
One batch with three months accelerated stability data reported in supplement; one batch on long-term stability data reported in annual report.
在补充申请资料中应提供一批3个月的加速稳定性试验数据；在年报中提供的一批长期稳定性试验数据。
Significant body of data not available: （未积累大量信息的情况）
Up to three batches with three months accelerated stability data reported in supplement; up to three batches on long- term stability data reported in annual report.
在补充申请资料中应提供3批3个月的加速稳定性试验数据；在年报中提供3批长期稳定性试验数据。
b. Dissolution Documentation 溶出试验资料
Case B: 情况B：
Multi-point dissolution profile should be performed in the application/compendial medium at 15, 30, 45, 60 and 120 minutes or until an asymptote is reached. The dissolution profile of the drug product at the current and proposed site should be similar.
多点溶出曲线的绘制，应选取申报资料/药典中规定的溶出介质，取样点应为15，30，45，60和120分钟或直至达到稳态。变更生产地点前后的产品溶出曲线应相似。
c. In Vivo Bioequivalence Documentation 体内生物等效性试验资料
None. 不需要
3. Filing Documentation 归档文件
Changes being effected supplement; annual report (long-term stability data). 实施变更的补充申请资料；年报（长期稳定性试验数据）。
V. CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN) 批量变更（生产规模的放大/缩小） Postapproval changes in the size of a batch from the pivotal/pilot scale biobatch material to larger or smaller production batches call for submission of additional information in the
application. Scale-down below 100,000 dosage units is not covered by this guidance. All scale-up changes should be properly validated and, where needed, inspected by appropriate agency personnel.
批准后，将生产规模从制备生物批的中试规模（pivotal/pilot scale）进行放大或缩小需要提交补充申请资料。生产规模缩小到10万剂量单位以下的变更不属于本指导原则范畴。对所有生产规模放大的变更均应进行合理的验证，并且必要时应由合适的代理人进行核查。
A. Level 1 Changes 1类变更
1. Definition of Level 定义
Change in batch size, up to and including a factor of 10 times the size of the pilot/biobatch, where: 1) the equipment used to produce the test batch(es) is of the same design and operating principles; 2) the batch(es) is (are) manufactured in full compliance with CGMP's; and 3) the same standard operating procedures (SOP's) and controls, as well as the same formulation and manufacturing procedures, are used on the test batch(es) and on the full-scale production batch(es).
生产规模的变更在原中试规模/生物批的10倍以内，并且与中试规模相比，1）试验批所用生产设备应具有相同的设计和工作原理；2）生产过程应完全符合cGMP的要求；3）试验批和全规模生产批应采用相同的标准操作规范、质量控制方法，以及相同的处方和生产步骤。 2. Test Documentation 试验资料
a. Chemistry Documentation 化学资料
Application/compendial release requirements. Notification of change and submission of updated batch records in annual report. One batch on long-term stability reported in annual report.
申报资料/药典要求的资料。批量变更声明和在年报中提交的新的批记录。 b. Dissolution Documentation 溶出研究资料
None beyond application/compendial release requirements. 申报资料/药典要求的资料，不需要其他资料。 c. In Vivo Bioequivalence 体内生物等效性资料
None. 不需要
3. Filing Documentation 归档文件
Annual report (long-term stability data).
年报（长期稳定性试验数据）
B. Level 2 Changes 2类变更
1. Definition of Level 定义
Changes in batch size beyond a factor of ten times the size of the pilot/biobatch, where: 1) the equipment used to produce the test batch(es) is of the same design and operating principles; 2) the batch(es) is (are) manufactured in full compliance with CGMP'S; and 3) the same SOP's and controls as well as the same formulation and manufacturing procedures are used on the test batch(es) and on the full-scale production batch(es).
生产规模的变更在中试规模/生物批的10倍以上，并且与中试规模相比，1）试验批所用生产设备应具有相同的设计和工作原理；2）生产过程应完全符合cGMP的要求；3）试验批和全规模生产批应采用相同的标准操作规范、质量控制方法，