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1、GUIDELINE No.:HGB(1)T-1Technical Guideline for Making Post Approval Changes to Chemical DrugProducts(I)1由于万维网使用者的数量飞速增长，对于最终用户来说，随着可供使用的主页和网上信息的数量的爆炸性增长，最终用户间的交互性越来越差，传统意义上的交互已经无法满足用户的需求，举一个简单的例子，即使是在世界杯的决赛期间，一个普通的足球迷也很难立刻从网络上找到聊天的对象。April 20082Table of contentsI. Overview2II. Basic principles for p
2、erforming studies post-approval changes to chemical drug products3III. Changes to Drug Substance Manufacturing Process6IV. Changes to excipients in a drug formulation14V. Changes to the manufacturing process for a drug product22VI. Changes to drug product strength and packaging size30VII. Changeto d
3、rug prodcugt specificication36VIII. Changes to the drug prodcut shelf-life (expiration dating period) and/or storage conditions41IX. Changes to drug product packaging materials and the container closure syatem . 37X. Changes to the manufacturing site of an imported drug product51XI. Change to the ma
4、nufacturing site of API used in an imported drug product and change to the manufacturing site of an imported API48XII. Changes in the site of Manufacture for API used in a domestic drug product. Error! Bookmark not defined.Appendix I Basic methods for comparison investigation of drug dissolution/rel
5、ease36Appendix II General considerations for exemption of in vivo bioequivalence (BE waiver) 72Appendix III A partial list of of medicines with narrow therapeutic windowsError!Bookmark not defined.References77Glossary79Authors801I. OverviewThis guideline is primarily used to guide pharmaceutical man
6、ufacturers to carry out studies for post-approval changes (or changes) to chemical drug products. Changes here refer to the changes that involve source, methods, control conditions with respect to the manufacture, quality-control and use condition and related areas for a drug product that has been a
7、pproved for marketing. These changes may affect the products safety, efficacy and quality controllability. The change study here refers to the study and qualification work to support a proposed change.At present, the changes and change studies covered in this guidelines include the following areas:
8、the changes to API/drug substance (DS) manufacturing process, excipient for pharmaceutical use in formulation and its manufacturing process, registered specifications, strengths, shelf life (expiration dating period), storage conditions , drug product packaging materials and container closure system
9、, the imported drug product manufacturing site, manufacturing site of imported API/DS or API/DS used in import drug products, and API manufacturing sites used in domestic drug products.This guideline describes from technical point of view the studies and qualifications that should be performed when
10、changes are to be made to the products. Pharmaceutical manufacturers should perform change studies and qualifications in accordance with the technical requirements of this guideline, and after the work is completed, submit supplemental application to appropriate food and drug regulatory authorities
11、according to the requirements of Drug Registration Regulation (DRR).In order to control the potential impact of a change to the safety, efficacy and quality controllability of the affected product, this guideline divides the all changes into 3 categories: Type I, minor changes that basically have no
12、 impact on the safety, efficacy and quality controllability of the affected product; Type II, moderate changes, for which studies should be performed to demonstrate that the changes have no effect on the safety, effectiveness and quality controllability of the affected product ; Type III, major chan
13、ges that need a series of studies to demonstrate that the changes have no negative impact on the safety, efficacy and quality controllability of the affected product. The category of change types has taken into consideration the relevant regulation for supplemental application in of the current Drug
14、 Registration and Regulation (DRR) as well as relevant technical requirements of other countries in order to help the manufacturers to perform targeted change studies, summarize the study results into supporting information and make supplemental application to the regulatory agencies.2The changes re
15、ferred to in this guideline are post approval changes aiming at marketed chemical drug products. Therefore, changes and change studies should be based on the studies and cumulative data in the past from the drug registration stage and actual manufacturing processes. The more systematic and thorough
16、the research work in registration phase was and the more sufficient the data were accumulated from the manufacturing processes, the more helpful it would be for the post-approval change study.For specific requirements in this guideline, please refer to the technical guidelines for chemical drug research and development or other relevant technical guidelines previou
