小中大For this, as well as for other reasons, equivalent does not necessarily mean identical. Equivalence may also relate to maintenance of a quality characteristic (e.g., stability) rather than a single performance of a test.
对此，和其它原因一样，等价并不是意味着相等。等价还可能关系到质量特征的维持（例如，稳定性）而不是简单的一项测试行为。
C. Adverse Effect 不良作用
Some manufacturing changes have an adverse effect on the identity, strength, quality, purity, or potency of the drug product. In many cases, the applicant chooses not to implement these manufacturing changes, but sometimes the applicant wishes to do so. If an assessment indicates that a change has adversely affected the identity, strength, quality, purity, or potency of the drug product, FDA recommends that the change be submitted in a prior approval supplement regardless of the recommended reporting category for the change. For example, a process change recommended for a changes-being-effected-in-30¬days supplement could cause the formation of a new degradant that requires qualification and/or identification.10 The applicant's degradation qualification procedures may indicate that there are no safety concerns relating to the new degradant. Even so, we recommend that the applicant submit this change in a prior approval supplement with appropriate information to support the continued safety and effectiveness of the drug product. During the review of the prior approval supplement, the FDA will assess the impact of any adverse effect on the drug product as this change may relate to the safety or effectiveness of the drug product.
一些生产变更对药品的特征、剂量、质量、纯度或药效有不良作用。在许多情况下，申请者选择不去实行这些生产变更，但有时申请者希望那样做。如果评估表明变更对药品的特征、剂量、质量、纯度或药效有不良影响，FDA建议这种变更将提交在批准前变更申请里而不管变更报告范围的建议。例如，一个工序的变更，能引起新降解产物的生成，要求其合格和/或能识别，建议30天后进行变更补充申请。申请者的降解合格操作可能表明没有关于新降解产物的安全隐患。即使如此，我们建议申请者在批准前变更申请中提交此变更，以适当的资料支持药品持续的安全性和有效性。
Applicants are encouraged to consult with the appropriate CDER chemistry or microbiology review staff if there are any questions on whether a change in a characteristic would be viewed by CDER as adversely affecting the identity, strength, quality, purity, or potency of the drug product.
不论药品的特征是否改变，CDER人员将当作影响药品特性、浓度、质量、纯度或药效的不利方面来检查，如果有任何问题，鼓励申请者咨询合适的CDER化学或微生物检查人员。
V. COMPONENTS AND COMPOSITION 成分和组成
Changes in the qualitative or quantitative formulation, including inactive ingredients, as provided in the approved application, are considered major changes requiring a prior approval supplement, unless exempted by regulation or guidance (§ 314.70(b)(2)(i)). The deletion or reduction of an ingredient intended to affect only the color of the drug product may be reported in an annual report (§ 314.70(d)(2)(ii)). Guidance on changes in components and composition that may be submitted in a changes-being-effected supplement or annual report is not included in this document because of the complexity of the recommendations, but may be covered in one or more guidance documents describing postapproval changes (e.g., SUPAC documents).
处方质量或数量改变，包括费活性成分，认为是大变更，要求提交“批准前变更申请”，除非有法规或指南豁免(§ 314.70(b)(2)(i))。只是影响药品颜色的某种成分的取消或减少可以在年度报告中报告(§314.70(d)(2)(ii))。本指南不包括在“有待生效的变更补充文件”或年度报告中提交的变更。
VI. MANUFACTURING SITES11 厂址
A. General Considerations
CDER must be notified when a manufacturer changes to a manufacturing site that is different from those specified in the approved application (314.70(a)). Sites can include those used by an applicant to (1) manufacture or process drug products,12 in-process materials, drug substances, or drug substance intermediates, (2) package drug products, (3) label drug products, and (4) test components, drug product containers, closures, packaging materials, in-process materials, or drug products. Sites include those owned by the applicant or contract sites used by an applicant. Testing sites include those performing physical, chemical, biological, and microbiological testing to monitor, accept, or reject materials, as well as those performing stability testing. Sites used to label drug products are considered those that perform labeling of the drug product's primary or secondary packaging components. Sites performing operations that place identifying information on the dosage form itself (e.g., ink imprint on a filled capsule) are considered to be facilities that manufacture or process the drug product. FDA recommends that the supplement or annual report identify whether the proposed manufacturing site is an alternative to or replacement for the site or sites provided for in the approved application.
当变更生产地址时，如果变更的地点不包括在批准的申请中，必须通知CDER(314.70(a))。生产地址变更的包括申请人用于制造或处理制剂药品、中控物料、原料药、原料药中间体，包装药品、贴标签，检测成分、药品容器、密封材料、包材、中控物料或药品的场所的地址变更厂址包括申请人所有的或合同场所。检测厂址包括物理、化学、生物学、微生物检测场所，用于物料控制、接收、拒收，以及稳定性检测。贴标签场所指对产品内包装和外包装贴标签的场所。FDA建议在增补或年度报告中必须说明提交的生产地址是否时原来已批准的地址的替代选择，还是完全替代地址。
FDA recommends that a move to a different manufacturing site, when it is a type of site routinely subject to FDA inspection, be submitted as a prior approval supplement if the site does not have a satisfactory CGMP inspection13 for the type of operation14 being moved (see sections VI.B.1 and 2).
搬迁后的另一个生产厂址如果只需进行常规检查，尚未通过GMP检查，FDA建议提交“批准前的变更申请”。
For labeling, secondary packaging, and testing site changes, the potential for adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product is considered to be independent of the type of drug product dosage form or specific type of operation being performed. Therefore, the recommended reporting category for any one of these manufacturing site changes will be the same for all types of drug products and operations. For manufacturing sites used to (1) manufacture or process drug products, in-process materials, drug substances, or drug substance intermediates or (2) perform primary packaging operations, the potential for adverse effect depends on factors such as the type of drug substance or drug product and operation being performed. Therefore, recommended reporting categories may differ depending on the type of drug product and operations.
对于贴标签、外包装和检测地点的变更，对关系到药品安全性或有效性的特性、剂量、质量、纯度或药效有不良作用的潜在因素，被认为独立于药品剂型或正在执行的具体操作。因此，建议这些生产场所任一变更的报告范围要和所有类型的制剂和操作一样。对于生产场所用于（1）生产药品、中控物料、原料药、原料药中间体（2）实行内包装的操作，潜在的不良反应，取决于该类型的原料药或药品和正在执行的操作。因此。建议报告类别可以不同于依赖该类制剂和操作。
Except for the situations described in sections VI.B.4, VI.C.1.b, and VI.D.5, construction activities at a manufacturing site or moving production operations within a building or between buildings at the same manufacturing site do not have to be reported to CDER.
除了描述VI.B.4, VI.C.1.b, and VI.D.5的情况，在生产场所或活动的生产操作里、在相同生产场所、一个建筑物或两个建筑物之间的建筑活动不需要报告给CDER 。
We recommend that a move to a manufacturing site that involves other changes (e.g., process, equipment) be evaluated as a multiple related change (see section XII) to determine the appropriate reporting category.
我们建议生产场所的移动牵涉到被看作是复杂的相关其他变更（例如，工序、设备），再决定合适的报告范围。
