发布时间 : 星期日 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
Guidance for Industry
Immediate Release Solid Oral Dosage Forms
Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, In
Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation
SUPAC-IR指导原则：速释口服固体制剂放大生产和批准后变更：化学、生产和控制，体外
溶出试验、体内生物等效性文件
Center for Drug Evaluation and Research (CDER)
November 1995
CMC 5
药品评价与研究中心
1995年11月
CMC 5
TABLE OF CONTENTS
目录
I. PURPOSE OF GUIDANCE （本指导原则的目的）. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 1 II. DEFINITION OF TERMS（术语定义）. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3 III.COMPONENTS AND COMPOSITION（辅料成分或组成的变更）. . . . . . . . . . . . . . . . . . . . . . . . .. 6 IV. SITE CHANGES（地点变更） . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 13 V. CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)（批量大小（放大/缩小）的变更）. .. . . . 16 VI. MANUFACTURING（生产变更） . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 VII. IN VITRO DISSOLUTION （体外溶出试验）. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 VIII. IN VIVO BIOEQUIVALENCE STUDIES （体内生物等效性）. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 IX. REFERENCES（参考文献） . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 APPENDIX A: NARROW THERAPEUTIC RANGE DRUGS（附录A：治疗窗狭窄药物）. . . . . . . . . A-1
GUIDANCE FOR INDUSTRY 1
IMMEDIATE RELEASE SOLID ORAL DOSAGE FORMS SCALE-UP AND POSTAPPROVAL CHANGES: CHEMISTRY, MANUFACTURING, AND CONTROLS, IN VITRO DISSOLUTION TESTING, AND IN VIVO BIOEQUIVALENCE DOCUMENTATION
速释口服固体制剂放大生产和批准后变更：化学、生产和控制，体外溶出试验、体内生物等效性文件
I. PURPOSE OF GUIDANCE（本指导原则的目的）
This guidance provides recommendations to sponsors of new drug applications (NDA's), abbreviated new drug applications (ANDA's), and abbreviated antibiotic applications (AADA's) who intend, during the postapproval period, to change: 1) the components or composition; 2) the site of manufacture; 3) the scale-up/scale-down of manufacture; and/or 4) the manufacturing (process and equipment) of an immediate release oral formulation.
本指导原则所提供的的建议适用于新药申请（NDA's）、仿制药申请（ANDA's）和抗生素仿制药申请（AANA’S）的企业的批准后变更，内容包括：1）成分或组分的变更；2）生产地点的变更；3）放大/缩小生产规模的变更；和/或4）生产过程（工艺和设备）的变更
This guidance is the result of: 1) a workshop on the scale-up of immediate release drug products conducted by the American Association of Pharmaceutical Scientists in conjunction with the United States Pharmacopoeial Convention and the Food and Drug Administration (FDA); 2) research conducted by the University of Maryland at Baltimore on the chemistry, manufacturing and controls of immediate release drug products under the FDA/University of Maryland Manufacturing Research Contract; 3) the drug categorization research conducted at the University of Michigan and the University of Uppsala on the permeability of drug substances; and 4) the Scale-Up and Post Approval Changes (SUPAC) Task Force which was established by the Center for Drug Evaluation and Research (CDER) Chemistry, Manufacturing and Controls Coordinating Committee to develop guidance on scale-up and other postapproval changes.
本指导原则是以下工作的成果：1）在美国药学科学家协会与美国药典委员会和FDA的指导下，进行速释药品放大生产的车间；2）在位于巴尔的摩的马里兰大学指导下，并在FDA/马里兰大学生产研究合同下的速释药品的化学、生产和控制的研究；3）在密歇根大学和乌普萨拉大学指导下的药品分类学研究中关于药物渗透性的研究；4）由药品评价和研究中心（CDER）化学、生产和控制协调委员会成立的放大生产和批准后变更（SUPAC）特别小组， 来制定关于放大生产和其它的批准后变更的指导原则。
The guidance defines: 1) levels of change; 2) recommended chemistry, manufacturing, and controls tests for each level of change; 3) in vitro dissolution tests and/or in vivo bioequivalence tests for each level of change; and 4) documentation that should support the change. For those changes filed in a “changes being effected supplement” *21 CFR 314.70(c)+, the FDA may, after a review of the supplemental information, decide that the changes are not approvable. This guidance thus sets forth application information that should be provided to CDER to assure continuing product quality and performance characteristics of an immediate release solid oral dose formulation for specified postapproval changes. This guidance does not comment on or otherwise affect compliance/inspection documentation that has been defined by CDER’s Office of Compliance or FDA’s Office of Regulatory Affairs. This guidance does not affect any
postapproval changes other than the ones specified. For changes not addressed in this guidance, or for multiple changes submitted at one time or over a short period of time, or where the number of batches needed for stability testing is not specified, sponsors should contact the appropriate CDER review division or consult other CDER guidances/guidelines to obtain information about tests and application documentation.
本指导原则规定了以下内容：1）变更的类别；2）针对每一类变更建议进行的药物化学、药品生产以及生产和质量控制（CMC）研究内容；3）针对每一类变更建议进行的体外溶出试验和/或体内生物等效性试验；和4）变更用的支持性文件资料。对于那些在“起补充作用的变更”文件，FDA在对补充资料进行审查后，可以决定是否允许这些变更。本指导原则给出了需递交给药品评价和研究中心（CDER）的申请信息，以确保速释口服固体制剂在发生规定的变更后继续保持其质量和性能特点。本指导原则不评论也不更改由CDER法律管理办公室或FDA法规事务办公室颁布的法规/检查文件。本指导原则不涉及除了本文提到的变更情形外的其他情形的批准后变更。对于那些本指导原则未涉及的变更，以及同时或短时间内申请多个变更，或需进行稳定性实验的批次数量未规定的，申请人应与CDER相关审评部门沟通，或者参考CDER其他的指导原则/指南以获得有关研究和申报资料的信息。
21 CFR 314.70(a) provides that applicants may make changes to an approved application in accordance with a guideline, notice, or regulation published in the FEDERAL REGISTER that provides for a less burdensome notification of the change (for example, by notification at the time a supplement is submitted or in the next annual report). This guidance permits less burdensome notice of certain postapproval changes within the meaning of § 314.70(a).
FDA 的法规（21 CFR 314.70(a)）规定申请人可以根据发表在联邦登记（Federal Register）上的指导原则、通知或条例的规定，对所批准的申请内容实施变更，如此可以减轻繁重的变更通告量（举例而言，可以在递交补充申请时或在下一年年报中予以通告）。对于符合§ 314.70(a)的某些批准后变更，本指导原则允许减少通告量。
For postapproval changes for immediate release dosage forms that affect components and composition, scale-up, site change, and manufacturing process or equipment changes, this guidance supersedes the recommendations in section 4.G of the Office of Generic Drugs Policy and Procedure Guide 22-90 (September 11, 1990). For all other dosage forms and changes, this guidance does not affect the recommendations in Guide 22-90.
当速释制剂的批准后变更涉及成份和组成、生产规模放大、生产地点变化和生产工艺或设备改变时，本指导原则将代替仿制药办公室（OGD）制定的 Policy and Procedure Guide 22-90 （September 11, 1990）章节 4.G中提供的建议。但对于所有其他的剂型和变更，本指导原则不适用，仍应遵循Guide 22-90中的建议。
II. DEFINITION OF TERMS术语的定义
A. Batch 批
A specific quantity of a drug or other material produced according to a single manufacturing order during the same cycle of manufacture and intended to have uniform character and quality, within specified limits [21 CFR 210.3(b)(2)].
在同一个生产周期中，按照相同的生产规程制备的特定数量的药品或其它物料，并意图使其性质和质量在规定的限度内具有一致性。 B. Contiguous Campus 毗邻区域