Guidance for Industry
生活大爆炸第六季19 Immediate Relea 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
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Center for Drug Evaluation and Rearch (CDER)
November 1995
CMC 5
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药品评价与研究中心
1995年11月
CMC 5
TABLE OF CONTENTS
I. PURPOSE OF GUIDANCE （本指导原则的目的）. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 1
II. DEFINITION OF TERMS（术语定义）. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3
IIIPONENTS AND COMPOSITION（辅料成分或组成的变更）. . . . . . . . . . . . . . . . . . . . . . . . .. 6
IV. SITE CHANGES（地点变更） . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 13
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V. CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)（批量大小（放大/缩小）的变更）. .. . . . 16
王子的前妻VI. MANUFACTURING（生产变更） . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
VII. IN VITRO DISSOLUTION （体外溶出试验）. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
man and computerVIII. IN VIVO BIOEQUIVALENCE STUDIES （体内生物等效性）. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
IX. REFERENCES（参考文献） . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
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GUIDANCE FOR INDUSTRY 1
IMMEDIATE RELEASE SOLID ORAL DOSAGE FORMS SCALE-UP AND POSTAPPRO
VAL 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 relea oral formulation.
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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 relea 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) rearch conducted by the University of Maryland at Baltimore on the chemistry, manufacturing and controls of immediate relea drug products under the FDA/University of Maryland Manufacturing Rearch Contract; 3) the drug categorization rearch 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 Rearch (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。
scdma是什么意思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 tho 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 ts forth application information that should be provided to CDER to assure continuing product quality and performance characteristics of an immediate relea solid oral do formulation for specified postapproval changes. This guidance does not comment on or otherwi 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 addresd 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).
