




版權(quán)說明:本文檔由用戶提供并上傳,收益歸屬內(nèi)容提供方,若內(nèi)容存在侵權(quán),請進(jìn)行舉報或認(rèn)領(lǐng)
文檔簡介
1、開發(fā)報批美國開發(fā)報批美國fda的仿制藥的仿制藥與相關(guān)問題探討與相關(guān)問題探討藥物制劑藥物制劑目標(biāo)主流市場目標(biāo)主流市場仿制藥研發(fā)團(tuán)隊concept-1 build up a teaminformationformulationproductregulatoryanalyticalbio-pharmaceuticalprojectlegelproduct development roadmap仿制藥的仿制藥的研發(fā)過程研發(fā)過程 quality acceptably low risk of failing to achieve the desired clinical attributes pharma
2、ceutical quality= f drug substance, excipients, manufacturing. qbd product and process performance characteristicsscientifically designed to meet specific objectives, not merely empirically derived from performance of test batcheswhat is qbd (?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?what is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)
3、?在制劑開發(fā)中怎么體現(xiàn)?essential elements of qbd definition of the quality target product profilehigh level quality aspects of the product: purity, drug release (dissolution/disintegration time), pharmacokinetic profile, etc. critical quality attributes (cqas) for drug product characteristics of dp which have
4、impact on desired profile conscious attempt to study and control critical process parameters (cpps) identification of material properties and process parameters which haveeffect on product cqas design space: the multidimensional combination and interaction ofinput variables and process parameters th
5、at have been demonstrated to provide assurance of quality identification of a control strategy for critical process parameterswhat is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialsequipmentenvironmentoperatorsvariable inputs x“l(fā)ocked” process=variable qualityhow did we work in the pastwhat is qbd?qbd
6、qbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialsequipmentenvironmentoperatorsunderstood variable inputsxunderstood and controlled process=predefined qualityflexible process design spacehow can we work in the futurewhat is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?what is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialswet
7、 granulationfluid bed dryingblendingcompressionproductdrug substanceexcipientssourceassayimpurities lodps what is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialswet granulationfluid bed dryingblendingcompressionwaterbindertempspray ratespeedtimep.swhat is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialsw
8、et granulationfluid bed dryingblendingcompressionwhat is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialswet granulationfluid bed dryingblendingcompressionair flowtemprhshock cyclep.s.what is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialswet granulationfluid bed dryingblendingcompressionfill volumerotat
9、ion speedend point (time)blend uniformitydensitiesangle of reposewhat is qbd?qbdqbd在制劑開發(fā)中怎么體現(xiàn)?在制劑開發(fā)中怎么體現(xiàn)?raw materialswet granulationfluid bed dryingblendingcompressionfeed frametoolingpunch penetration depthcompression forcepress speedfeeder speed examples of qbd questions under qbr control of drug
10、 substance what is the drug substance specification? does it include all the critical drug substance attributes that affect the manufacturing and quality of the drug product? (2 pages) drug product what attributes should the drug product possess? (1.5 pages) how were the excipients and their grades
11、selected? how was the final formulation optimized? manufacturing process how are the manufacturing steps (unit operations) related to the drug product quality? how were the critical process parameters identified, monitored, and/or controlled? pharmaceutical development manufacture container closure
12、systemaspectstraditionalqbdpharmaceuticaldevelopmentempirical; univariateexperimentssystematic; multivariateexperimentsmanufacturingprocessfixed; validation on 3 initialfull-scale batches; focus on reproducibilityadjustable within design space; continuous verification;focus on control strategyproces
13、s controlin-process testing for go/nogo; offline analysis w/slow responsepat utilized for feedback &feed forward, real timeproductspecificationprimary means of qualitycontrol; based on batch datapart of the overall qualitycontrol strategy; based ondesired product performancecontrolstrategymainly by
14、intermediate andend product testingrisk-based; controls shiftedupstream; real-time releasereactive to problems &oos; post-approvalcontinuous improvementenabled within design spaceqbdqbd小結(jié)小結(jié)-summary-summary研發(fā)研發(fā)( (高難高難) )仿制藥的一些體仿制藥的一些體會會dissolution profile-體外溶出曲線體外溶出曲線生物等效生物等效(be)結(jié)果結(jié)果auc0-tauc0-infcma
15、xfastratio108.01%108.12%86.26%90% geometric c.i.103.49% to 112.73%103.64% to 112.79%75.28% to 98.84%fedratio111.21%112.48%85.24%90% geometric c.i.104.40% to 118.47%105.78% to 119.60%73.47% to 98.90%summary of in vivo study results of test formulation vs. rld原因調(diào)查原因調(diào)查product p data (log transformed da
16、ta, fast, n-12)ratio of geometric means x 10090% ci of log transformed datacv (%)test a vs referenceauc10690.4; 12322.0cmax10480.1; 13436.4test b vs referenceauc133114; 15522.0cmax129100; 16736.4product p data (log transformed data, fed, n-11)ratio of geometric means x 10090% ci of log transformed d
17、atacv (%)test a vs referenceauc96.175.4; 12332.7cmax10983.5; 14135.3test b vs referenceauc92.472.5; 11832.7cmax10983.7; 14135.3product p data (log transformed data)ratio of geometric means x 10090% ci of log transformed datacv (%)fastauc10293; 11133,9cmax10594.5; 11638.8fedauc98.891.6; 10726.4cmax99.689.2; 11138.4案例研究案例研究-4api is water soluble. prototype formulation was proposed based on in vitro dissolution (
溫馨提示
- 1. 本站所有資源如無特殊說明,都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請下載最新的WinRAR軟件解壓。
- 2. 本站的文檔不包含任何第三方提供的附件圖紙等,如果需要附件,請聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
- 3. 本站RAR壓縮包中若帶圖紙,網(wǎng)頁內(nèi)容里面會有圖紙預(yù)覽,若沒有圖紙預(yù)覽就沒有圖紙。
- 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
- 5. 人人文庫網(wǎng)僅提供信息存儲空間,僅對用戶上傳內(nèi)容的表現(xiàn)方式做保護(hù)處理,對用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯,并不能對任何下載內(nèi)容負(fù)責(zé)。
- 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容,請與我們聯(lián)系,我們立即糾正。
- 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時也不承擔(dān)用戶因使用這些下載資源對自己和他人造成任何形式的傷害或損失。
最新文檔
- 短視頻平臺內(nèi)容監(jiān)管與網(wǎng)絡(luò)生態(tài)治理創(chuàng)新研究與實(shí)踐報告
- 數(shù)字孿生視角下2025年城市規(guī)劃與建設(shè)中的智慧城市能源管理系統(tǒng)優(yōu)化與評估優(yōu)化優(yōu)化報告
- 2025年智慧交通系統(tǒng)交通流量預(yù)測技術(shù)智能交通數(shù)據(jù)挖掘與智能控制報告
- 工業(yè)互聯(lián)網(wǎng)平臺微服務(wù)架構(gòu)性能測試報告2025:邊緣計算與實(shí)時性能優(yōu)化
- 電競商業(yè)贊助策略報告:2025年品牌合作案例分析
- 功能性飲料在健身器材銷售中的市場推廣策略報告
- 培訓(xùn)班門店財務(wù)管理制度
- 亞馬遜銷售組長管理制度
- 早餐健康宿舍管理制度
- 房產(chǎn)公司運(yùn)營部管理制度
- 福建省福州市2023?2024學(xué)年高一下冊期末考數(shù)學(xué)試卷附解析
- 2025年宜賓市英語七下期末復(fù)習(xí)檢測試題含答案
- 項目管理從立項到結(jié)項全解析
- 全國導(dǎo)游人員資格考試單科綜合測試卷(科目一:政策與法律法規(guī))
- 2024年中國鐵路成都局集團(tuán)有限公司招聘考試《鐵路基本常識》真題庫及答案
- 中醫(yī)診斷學(xué)考點(diǎn)總結(jié)
- 生態(tài)草場使用權(quán)轉(zhuǎn)讓協(xié)議
- 第18課清朝的邊疆治理教學(xué)設(shè)計-統(tǒng)編版七年級歷史下冊
- 物流實(shí)操試題及答案詳解
- 播出設(shè)備檢修管理制度
- 國家開放大學(xué)學(xué)習(xí)網(wǎng)電大證券投資分析形考任務(wù)12345答案
評論
0/150
提交評論