【正文】 to acplish this? ? Were any other formulation alternatives investigated and how did these perform? ? Were any formulation optimization or sensitivity studies carried out for variations in position around the final formulation? Were these studies sufficient to establish a design space for formulation position? ? Is the formulation design consistent with the dosage form classification in the label? ? Drug Product ? What are the critical quality attributes that ensure the product will perform as labeled? QBR: Process Development Report ? Process Description ? Why was this manufacturing process selected for this drug product? ? Were alternative unit operations investigated by process development studies? ? Critical Steps and Scale Up ? How were the critical steps in the process identified? ? What are the critical process parameters for each critical step and how were they identified, monitored and/or controlled? ? Were process development studies that varied starting materials or operating parameters conducted? Were these studies sufficient to establish a design space for process? ? In process tests ? Why is each in process test required? ? How were the acceptance limits chosen? ? Why were the inprocess tests identified as critical to product quality? ? What scaleup experience does the sponsor have with the unit operations in this process? QBR: Risk Summary ? NTI drug ? Classified as a nonNTI drug, risk score = + 0 ? Classified as an NTI drug, risk score = +1 ? Dosage Form ? Simple Dosage Form, risk score = + 0 ? Other Dosage Forms and NTI drugs, risk score = + 1 ? Development Report ? If the sponsor submits a development report that addresses the FDA’s questions: Risk score = + 0 ? Solution and IR Products: Product Development Report ? Other Dosage Forms: Product and Process Development Reports ? Insufficient or missing development report, risk score = + 1 ? If the application is of high overall quality ? Less than or equal to 2 cycles, risk score = + 0. ? Greater than 2 cycles, risk score = + 1 QBR: RiskBased Conclusion ? Should the application be approved? ? What postapproval waivers/mitments are appropriate for this product? ? If the total risk score is less than or equal to 1 ? CBE0 and CBE30 changes may be in annual reports ? Many PAS to CBE 30 ? If the total risk score is greater than 1 ? All supplements should be submitted as usual 生物等效性豁免 ?生物等效性豁免是指基于體外數(shù)據(jù)審批的管理程序。固體制劑往往采用溶出度、釋放度作為證據(jù)。 I、 基于藥物劑型的生物等效性豁免 ?只有供試品和參比制劑的原料及其含量一致，輔料一致、用量相當(dāng)，且符合如下規(guī)定時，可生物等效性豁免： 注射液； 口服溶液，含量一致，且不含已知會影響胃腸道功能和主藥稀釋的輔料； 氣體；溶液散劑； 耳用或眼用溶液；、 外用溶液； 采用同樣裝置使用的吸入劑或鼻噴劑。 II、基于劑型劑量比例的生物等效性豁免 ?當(dāng)最高劑量的 BE數(shù)據(jù)具備時，下列情況可生物等效性豁免： 同樣的劑型； 主藥和輔料的比例相當(dāng)； 對于緩釋制劑，同樣的釋放機(jī)制； 溶出度相似因子符合規(guī)定； 比例變化在線性動力學(xué)范圍內(nèi)。 III、基于 BCS分類的生物等效性豁免 FDA在其指南中指出：制劑分別在 900ml 、 中采用籃法 100rpm或漿法 50或 75rpm下依法測定，藥物制劑可以分為：（ 1）極快速溶出： 15分鐘內(nèi)溶出量不低于 85%；（ 2）快速溶出： 30分鐘內(nèi)溶出量不低于 85%；（）緩慢溶出：溶出 85%需要 30分鐘以上。 生物等效性豁免條件：仿制品和參比制劑在上述條件下屬于同一類別，且相似性分析符合規(guī)定，相似性標(biāo)準(zhǔn)如下分類： ? 分類 I （ FDA和 WHO均認(rèn)可）： BCS I類藥物的制劑且符合其中之一： 在上述三種條件下不超過 30分鐘溶出 85%以上，相似因子f250； 參比制劑和受試制劑均為極快速溶出。 ? 分類 II （ WHO認(rèn)可）： BCS II類藥物，但在 的制劑且符合其中之一： 在 ； 在三種介質(zhì)中的溶出行為與參比制劑相似性符合要求。 ? 分類 III （ WHO認(rèn)可）： BCS III類藥物： 參比制劑和受試制劑均為極快速溶出，且不含已知可改變胃腸道運(yùn)動或主藥通透性的輔料； 企業(yè)應(yīng)證明輔料的質(zhì)量與使用目的相符。如使用的為新輔料或使用大量的常用輔料，應(yīng)說明其對生物利用度的影響。 三、我國仿制藥的申報、審評和研發(fā)對策 ?新藥新、仿制藥同、新劑型特 ?兩報兩批 ?豁免生物等效性試驗(yàn)： 注射液； 外用制劑； Company Logo ?我國仿制藥申報流程圖 Technology 美國 2023年仿制藥占處方藥市場比例 70%以上，處于仿制藥消費(fèi)大國之首 （產(chǎn)品從 150個國家進(jìn)口）；德國、英國的仿制藥也已超過 50%。 國外仿制藥現(xiàn)狀 中國仿制藥產(chǎn)業(yè)發(fā)展的機(jī)遇 機(jī)遇與挑戰(zhàn) 中國仿制藥產(chǎn)業(yè)發(fā)展的挑戰(zhàn) ? 國內(nèi)老齡化，城鎮(zhèn)化加速造成的醫(yī)改和對仿制藥的要求急劇增加 ? 10年內(nèi)專利藥幾種到期造成了仿制藥的戰(zhàn)略機(jī)遇 ? 部分企業(yè)已經(jīng)開始國際標(biāo)準(zhǔn)的注冊和海外戰(zhàn)略，取得了積極進(jìn)展 ? 整體研發(fā)技術(shù)水平低 ? 缺乏仿制藥制劑的國際注冊經(jīng)驗(yàn)，制劑產(chǎn)品很少進(jìn)入發(fā)達(dá)國家市場，國際競爭力不強(qiáng) ? 缺乏國際標(biāo)準(zhǔn)和通行質(zhì)量規(guī)范，質(zhì)量管理的理念和管理水平與國際水平尚有明顯差距，造成了產(chǎn)品國際競爭能力不足 LOGO LOGO 謝謝觀看 /歡迎下載 BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES. BY FAITH I BY FAITH