工藝驗(yàn)證方案

1、*制藥廠(chǎng)* Factory86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382( P)共35頁(yè)第1頁(yè)86 (300mg )工藝驗(yàn)證方案PROCESS VALIDATIONPROTOCOL文件編號(hào)File codeV-0382 ( P)版本 VersionV 01頁(yè)數(shù)Page共35頁(yè)修訂記錄History修訂本Version修訂日期Date修訂/更改要求的原因Reason修訂者By*公司*制藥廠(chǎng)* Factory86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOC

2、OL文件編號(hào)File#V-0382（ P）共35頁(yè)第2頁(yè)作者簽名 Signature of th authoro您的簽名表明這份文件的準(zhǔn)備（編制 /修訂）符合企業(yè)驗(yàn)證主計(jì)劃、工藝驗(yàn)證主計(jì)劃、GMP規(guī)范和企業(yè)生產(chǎn)的要求，并且充分反映了工藝驗(yàn)證全過(guò)程中應(yīng)完成的必要任務(wù)，可以付諸對(duì)86工藝驗(yàn)證的實(shí)施。The signature means the drafting/revising confirms to validation master plan, process validation master plan, GMP,and in-house specifications. It includ

3、es all the contents need to be validated that can be applied to the process validationof 86 tablets.姓名Name職稱(chēng)/職務(wù)Title部門(mén) Department簽名 Signature日期Date驗(yàn)證主管Validation supervisorQA審核簽名 Checking signature您的簽名表明您已經(jīng)仔細(xì)審閱了本文件，確認(rèn)它正確并已全面反映了驗(yàn)證任務(wù)，可以付諸對(duì)86工藝驗(yàn)證的實(shí)施。The signature means the protocol is checked thoroughl

4、y and carefully. It includes all the contents need to be validated that can be applied to the process validation of 86 tablets.姓名Name職稱(chēng)/職務(wù)Title部門(mén) Department簽名 Signature日期Date*咅B(yǎng)長(zhǎng) ManagerQA*咅B(yǎng)長(zhǎng) Manager生產(chǎn)部Manufacture Department*部長(zhǎng) ManagerQC批準(zhǔn)簽名Approv a Signaturer您的簽名表明這份文件符合企業(yè)驗(yàn)證主計(jì)劃、工藝驗(yàn)證主計(jì)劃、企業(yè)生產(chǎn)檢驗(yàn)標(biāo)準(zhǔn)以及現(xiàn)

5、行的GMP規(guī)范，并且在此包含的文件和信息是充分的，并可直接應(yīng)用。The signature means the drafting/revising confirms to validation master plan, process validation master plan, GMP,and in-house specifications. It includes all the contents need to be validated that can be applied directly.姓名Name職稱(chēng)/職務(wù)Title部門(mén) Department簽名 Signature日期Dat

6、e*質(zhì)量廠(chǎng)長(zhǎng)Quality-director廠(chǎng)部Director's Office*廠(chǎng)長(zhǎng) Director廠(chǎng)部Director's Office*制藥廠(chǎng)* Factory86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共35頁(yè)第3頁(yè)TABLE OF CONTENTS1 目的 OBJECTIVES 32 驗(yàn)證范圍 SCOPE3.3 方案審查 PROTOCOL REVIEWING 34 組織與責(zé)任 RESPONSIBILITIES45 概述 INTRODUC TION46 處方、工藝流程

7、和驗(yàn)證關(guān)鍵控制項(xiàng)目FORMULATION/PROCESS/ CRITICAL PARAMETERS INVALIDATION 56.1 處方 FORMULATION56.2 工藝流程 PROCESS6.6.3 驗(yàn)證關(guān)鍵控制項(xiàng)目CRITICAL PAR AMETERS IN VALIDATION 77 驗(yàn)證用物料及主要設(shè)備 RAW MATERIALS AND EQUIPMENTS 97.1原輔料和包衣材料進(jìn)行確認(rèn)RAW MATER IALS CHECK97.2 主要設(shè)備進(jìn)行確認(rèn)EQUIPMENTS C HECK98 驗(yàn)證程序及內(nèi)容VALIDATION PROC EDURE AND CONTENT

8、 98.1 配料 DI SPENSING108.2 漿液的配制 GRANULATION SOLUTION PR EPARATION 108.3 干粉混合 DRY MIXING 118.4 制粒 GRANULATION118.5 濕顆粒整粒 WET MILLING128.6 沸騰干燥 FLUID BED DRYING 128.7 干顆粒整粒 DRY MILLING148.8 總混 MIXING 168.9 壓片 COMPRESSION 208.10 包衣 COATING 249 偏差分析與說(shuō)明 DEVIATION ANALYSIS AND EXPLANATION 3210 驗(yàn)證結(jié)果分析和結(jié)論VA

9、LIDATION RESULTS AND CONCLUSION 3311 參考文獻(xiàn) REFERENCE 3412 附件 APPENDICES 34名稱(chēng)：偏差清單DEVIATION LIST 35*制藥廠(chǎng)* Factory86( 300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382( P)共35頁(yè)第4頁(yè)1 目的 OBJECTIVES為了驗(yàn)證86 (300mg)的生產(chǎn)工藝規(guī)程，確保大生產(chǎn)的穩(wěn)定性，在本廠(chǎng)現(xiàn)有的設(shè)備和環(huán)境條件下連續(xù) 驗(yàn)證生產(chǎn)三批的86，批量為100萬(wàn)片，對(duì)生產(chǎn)中的關(guān)鍵步驟和工藝參數(shù)進(jìn)行確認(rèn)。批號(hào)待定。In o

10、rder to confirm the manufactur ing process of 86 tablets(300mg), 3 consecutive batches of 1.00 million 86tablets will be produced on the arranged equipments under the current environment condition. The critical stage and parameters will be finalized in the process to ensure the robustness of the reg

11、ular production. The batch number will be arranged in validating.2驗(yàn)證范圍SCOPE本方案適用于生產(chǎn)潔凈區(qū)一線(xiàn)設(shè)備的86的工藝驗(yàn)證。The protocol is applied to the process validation of 86 tablets(300mg) that produced in work line 1.3 方案審查 PROTOCOL REVIEWING下列時(shí)機(jī)應(yīng)對(duì)本方案進(jìn)行審查以確保方案的適宜性Review the protocol in the following condition產(chǎn)品處方發(fā)生變更

12、；Changing formulation產(chǎn)品的工藝步驟、工藝參數(shù)和批量發(fā)生變更;Changing process, parameters and batch size產(chǎn)品所使用的原料供應(yīng)商發(fā)生變更；Changing raw materials supplier產(chǎn)品所使用的原料的生產(chǎn)工藝發(fā)生變更；Changing raw materials manufacturing process產(chǎn)品所涉及的設(shè)施設(shè)備發(fā)生變更；Changing equipments產(chǎn)品的生產(chǎn)環(huán)境發(fā)生變更；Changing manufacturing environment86 (300mg)工藝驗(yàn)證方案86 (300mg)

13、PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382 ( P)共35頁(yè)第5頁(yè)4 組織與責(zé)任 RESPONSIBILITIES這些任務(wù)和責(zé)任可以適當(dāng)定義，按照他們的分工具體定義每項(xiàng)任務(wù)和責(zé)任。Properly define the responsibilities according to the tasks.姓名職稱(chēng)/職務(wù)Title部門(mén)職責(zé) Responsibilities*部長(zhǎng)ManagerQA對(duì)工藝驗(yàn)證提供全面的指導(dǎo)，以符合廠(chǎng)驗(yàn)證方針Guides the validation and ensures the confirmation of in-house v

14、alidationpolicy監(jiān)督方案的執(zhí)行，確定方案中要求的測(cè)試項(xiàng)目有完整和適當(dāng)?shù)臅?shū)面 報(bào)告Monitors the whole execution and ensures the process is thoroughly documented在方案執(zhí)行的過(guò)程中對(duì)取樣工作提供人員幫助Supports sampling對(duì)檢驗(yàn)數(shù)據(jù)及最終報(bào)告進(jìn)行復(fù)核及批準(zhǔn)Checks and approves the test data and final report*部長(zhǎng)Manager生產(chǎn)部ManufactureDepartment在方案執(zhí)行的過(guò)程中對(duì)產(chǎn)品的生產(chǎn)及設(shè)備的操作提供人員幫助Support man

15、ufacturing process and equipment operation對(duì)檢驗(yàn)數(shù)據(jù)及最終報(bào)告進(jìn)行復(fù)核及批準(zhǔn)Checks and approves the test data and final report*部長(zhǎng)ManagerQC在方案執(zhí)行過(guò)程中負(fù)責(zé)樣品的檢驗(yàn)工作Support lab analysis對(duì)檢驗(yàn)數(shù)據(jù)及最終報(bào)告進(jìn)行復(fù)核及批準(zhǔn)Checks and approves the test data and final report*質(zhì)量廠(chǎng)長(zhǎng)Quality-director廠(chǎng)部Director's Office對(duì)檢驗(yàn)數(shù)據(jù)及最終報(bào)告進(jìn)行復(fù)核及批準(zhǔn)Checks and app

16、roves the test data and final report*廠(chǎng)長(zhǎng)Director廠(chǎng)部Director's Office對(duì)檢驗(yàn)數(shù)據(jù)及最終報(bào)告進(jìn)行復(fù)核及批準(zhǔn)Checks and approves the test data and final report5 概述 INTRODUCTION86( 86 Tablets)* 類(lèi)藥，用于 * 等。在完成86實(shí)驗(yàn)室小試及批量試生產(chǎn)的基礎(chǔ)上，86進(jìn)行工藝驗(yàn)證(一線(xiàn))，連續(xù)生產(chǎn)三批，規(guī)格為300mg,生產(chǎn)批量為100萬(wàn)片，驗(yàn)證關(guān)鍵工藝參數(shù)，并證明該生產(chǎn)線(xiàn)有能力生產(chǎn)岀質(zhì)量均一、工藝穩(wěn)定可靠的86，且符合本廠(chǎng)內(nèi)控標(biāo)準(zhǔn)。batches wil

17、l be validated on work line 1. TheOn the base of 86 (300mg) lab and manufacture trial, the 3 consecutivebatch size is 1.00 million tablets. In the stage, the critical parameters will be confirmed to ensure the robustness of the86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共

18、35頁(yè)第6頁(yè)process in regular production that can supply in- house and A ' s specificatioomplied 86 tablets.6 處方、工藝流程和驗(yàn)證關(guān)鍵控制項(xiàng)目FORMULATION/PROCES S/E S CRITICALA PARAMETERSINVALIDATION6.1 處方 FORMULATION6.1.1 86生產(chǎn)處方（每100萬(wàn)片為一批號(hào)，制漿液分 2批，制粒分10料）Batch size is 1.00 million tablets. Granulation solution is s

19、eparated into 2 sub-batches, granule into 10s工序ib-batche骨口. 序號(hào)S成份物料代碼（Kg）/批（理論量）（Kg）/批（實(shí)發(fā)量）*液 漿 制2*3*制粒12總混12理論片重（g）86（ 300mg）工藝驗(yàn)證方案86 （300mg）文件編號(hào)File#V-0382（ P）共35頁(yè)第7頁(yè)VALIDATION PROTOCOL*制藥廠(chǎng)* Factory*制藥廠(chǎng)* Factory外加物料 33558275粒徑分布、外觀(guān)、異物檢查Screen analysis test合格Pass安全篩、磁力棒Security screen,magnetic grac

20、e丿總混Mixi ng不合格 Rejected偏差調(diào)查偏高 Higher偏差調(diào)查 Deviation Deviation偏低 Lower*制藥廠(chǎng)* Factory86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382 ( P)共35頁(yè)第8頁(yè)接上圖Cont' d工序關(guān)鍵控制項(xiàng)目關(guān)鍵項(xiàng)目說(shuō)明濕顆粒每料制粒終點(diǎn)時(shí)的制粒時(shí)間、加漿量、 攪拌速度、切割速度和力矩制粒時(shí)間、加漿量、攪拌速度、切割速度和力矩接影響濕顆粒的形成效果。沸騰干燥干燥時(shí)間、進(jìn)風(fēng)風(fēng)量、實(shí)際進(jìn)風(fēng)溫度、 物料溫度、出風(fēng)溫度并測(cè)定水分干燥時(shí)間、進(jìn)風(fēng)風(fēng)量

21、、實(shí)際進(jìn)風(fēng)溫度、物料溫度、 出風(fēng)溫度直接影響濕顆粒干燥的效果。水分測(cè)試作 為判斷干燥是否合格的依據(jù)。干顆粒整粒水分、粒徑分布、性狀、異物檢測(cè)和物 料溫度水分、粒徑分布、性狀、異物檢測(cè)和物料溫度作為判斷整粒后干顆粒是否合格的依據(jù)。干顆?？偦焖?、異物、性狀、含量、篩分試驗(yàn)和 松密度水分、異物、性狀、含量、篩分試驗(yàn)作為判斷總混 后干顆粒是否合格的依據(jù)。松密度僅為數(shù)據(jù)積累。壓片平均厚度、硬度、外觀(guān)、脆碎度、片重、 平均片重、金屬片檢測(cè)、壓片機(jī)轉(zhuǎn)速、 溶出和含量金屬片檢測(cè)、壓片機(jī)轉(zhuǎn)速直接影響壓片的效果。 均厚度、硬度、外觀(guān)、脆碎度、片重、平均片重、 溶出和含量作為判斷壓片后素片是否合格的依據(jù)。包衣出風(fēng)

22、溫度、空氣流量、噴量、片床和噴 嘴完好性檢查、外觀(guān)。性狀、鑒別A、鑒別B、片重差異、溶出度和微生物出風(fēng)溫度、空氣流量、噴量、片床和噴嘴完好性檢 查、外觀(guān)直接影響素片包衣的效果。性狀、鑒別 鑒別B、片重差異、溶出度和微生物作為判斷包衣 片是否合格的依據(jù)。IN VALIDATION平A、86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382( P)共35頁(yè)第9頁(yè)6.3 驗(yàn)證關(guān)鍵控制項(xiàng)目CRITICALA PARAMETERS*制藥廠(chǎng)* Factory86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS

23、 VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共35頁(yè)第10頁(yè)7 驗(yàn)證用物料及主要設(shè)備RAW MATERIALSL AND EQUIPMENTS7.1原輔料和包衣材料進(jìn)行確認(rèn)RAW MATERIALSL CHECK物料名稱(chēng)供貨單位原料*輔料*包衣材料*7.2主要設(shè)備進(jìn)行確認(rèn) EQUIPMENTS CHECK工序設(shè)備名稱(chēng)設(shè)備型號(hào)設(shè)備編號(hào)驗(yàn)證編號(hào)驗(yàn)證日期ProcessEquipmentTypeEINValidation#Validation Date制粒三相濕法顆粒機(jī)Granulation3-phase granulator干燥沸騰干燥機(jī)DryingFluid bed

24、 dryer*整粒液壓提升整粒機(jī)*MillingHydraulic lift miller總混自動(dòng)提升料斗混合機(jī)*MixingAuto-lifting tote blender壓片高速壓片機(jī)CompressionHigh speed presser包衣無(wú)孔包衣機(jī)CoatingCoating pan*8 驗(yàn)證程序及內(nèi)容 VALIDATION PROCEDU AND CONTENT86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共35頁(yè)第11頁(yè)&1 配料 DISP NSI將制粒的原輔料和外加輔料

25、按下表配料:Dispense API, excipients, additional excipients according to the table:工序Process原輔料名稱(chēng)API and excipients用于制粒的配料（Kg）外加輔料配料（KgAdditional material1）理論量（Kg）Theoretical qty .制漿液*廠(chǎng)oi gianulaiion*Granulation*solution*制粒*Granulation*混合*Mixing*注：本批產(chǎn)品制粒階段共分10料進(jìn)行制粒、干燥及整粒，每料按以下程序同法操作，最后將10料合為1批進(jìn)行總混。NOTE: T

26、h wholebatch will bseparated into 10 sub-batchesin granulation, dryiand dry milling.g Alll thesub-batchesare produced the sa combinedwa asa following.g InI theth mixing,g theth 10 sub-batches areto forthe whol batch.8.2 漿液的配制 GRANULATION SOLUTIONPREPARATION稱(chēng)量純化水*kg放入一個(gè)干凈的、大小適量的不銹鋼容器內(nèi)，攪拌的同時(shí)，慢慢地加入*kg，

27、*kg，混合15分鐘后（加蓋混合），然后打開(kāi)循環(huán)泵混合至少 15分鐘，最后稱(chēng)重。同法共配制2批。Weigh *kg purified water, and pour into the clean SSL container. Gradually add * and * with continuous stirring.Put the lid on container, mixing for 15 minutes. Switch on the recirculation pump and mix 15 minutes at least. Weigh the final solution. Pro

28、duce 2 batches by the same way. All the sub-batches are produced the same way.86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382 ( P)共35頁(yè)第12頁(yè)&3干粉混合 DRY MIXING將配好料的一料原*kg、*倒入Glatt-VG300三相濕法造粒機(jī)內(nèi)加蓋，設(shè)置攪拌速度160rpm,切割速度2000rpm,預(yù)混5分鐘，混合均勻。同法混合其余料次。Transfer the * (one sub-batch in granu

29、lation) to Glatt-VG300 granulator. Then, cover, set chopping speed at160rpm, cutting speed at 2000rpm, dry mix for 5 minutes. All the sub-batches are mixed by the same way.&4 制粒 GRANULATION將噴嘴裝入鍋內(nèi)10cm，并且扇型面與鍋壁垂直。用噴嘴以1 ±).2kg/min的加漿速度，將*kg (目標(biāo)值*Kg )的漿液加到 Glatt-VG300三相濕法造粒機(jī)內(nèi)，同時(shí)以攪拌速度160rpm，切割速

30、度2000rpm攪拌，最終攪拌力矩為*-*% (目標(biāo)值*% )。當(dāng)力矩到達(dá)* %時(shí)，停機(jī)，開(kāi)蓋，目測(cè)評(píng)價(jià)力矩達(dá)到*%時(shí)的顆粒狀況，繼續(xù)觀(guān)察直到達(dá)到想要的目標(biāo)為止The spray nozzle should be setted into 10 cm depth and have a vertical position with inner bowel surface.Spray *kg(target *Kg) granulation solution through nozzle at the speed of 1 0.2kg/min into Glatt-VG300 granulator,

31、while setchopping speed at 160rpm, cutting speed at 2000rpm. The granulation terminal is from *-*% (target at *%) loading.Visually evaluate the granulation at *% load reading, continue to visually evaluate until the target have been met .將每料制粒終點(diǎn)的制粒時(shí)間、加漿量、攪拌速度、切割速度、力矩記錄表1。Record the granulation time,

32、 granulation solution quantity, chopping speed, and cutting speed in table 1.86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382 ( P)共35頁(yè)第13頁(yè)表1制粒工藝參數(shù)TABLE 1 GANULATION PARAMETERS項(xiàng)目Item批號(hào) Batch#：可接受標(biāo)準(zhǔn)Specification1234567891011121314時(shí)間Time(mi n)/加漿量(kg)Solution qty.*-*kg (目標(biāo)值target *K

33、g )攪拌速度(rpm)Choppingspeed160rpm切割速度(rpm)Cutting speed2000rpm力矩 Load(%)*-*% (目標(biāo)值target *% )結(jié)論 Comments :&5濕顆粒整粒WET MILLI將制好的軟材用 GSF-180濕顆粒整粒，開(kāi)始時(shí)攪拌轉(zhuǎn)速度為5rpm，后隨制粒鍋內(nèi)的顆粒減少而逐漸提高攪拌轉(zhuǎn)速到160rpm,直接通過(guò)*英寸方孔錐形篩。Pass granule through GSF-180 wet mill and* inch sieve. Start milling with the beginning speed at 5 rp

34、m, with thedecrease of material, speed up to 160rpm.&6 沸騰干燥 FLUID BED DRYING每料分別干燥。整粒后的濕顆粒放入沸騰容器內(nèi)（物料腔），直接轉(zhuǎn)入GHIBLI-100沸騰干燥機(jī)中按上升鍵，將物料腔與進(jìn)風(fēng)腔和出風(fēng)腔密閉。設(shè)定間隔60秒；抖動(dòng)時(shí)間2秒；進(jìn)風(fēng)溫度*-* C （目標(biāo)值:* C）；風(fēng)機(jī)轉(zhuǎn)速 3000rpm ;空氣流量 1500 2500 m3/h （目標(biāo)值：* m 3/h）;岀風(fēng)溫度* C。當(dāng)岀風(fēng)溫度發(fā)生 2C或以上跳躍時(shí)，停止沸騰，拉岀物料腔，依照文件*在沸騰床中心位置用取樣棒抽取5克樣品過(guò)12目篩后，用快速水

35、分測(cè)定儀按模式,5方法1,設(shè)置105C測(cè)量干顆粒水分，目標(biāo)值86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382 ( P)共35頁(yè)第14頁(yè)為1.5%-2.0%。若水分超過(guò)2.0%，繼續(xù)干燥，設(shè)置間隔30秒；風(fēng)機(jī)轉(zhuǎn)速2500rpm；進(jìn)風(fēng)溫度*-* C；空氣流量1000 1800m3/h (目標(biāo)值：*m 3/h);出風(fēng)溫度*-* C,取顆粒測(cè)定顆粒的水分，重復(fù) 干燥直到水分達(dá)到可接受標(biāo)準(zhǔn)，目標(biāo)值為1.5%-2.0%。若水分超過(guò)2.0%，繼續(xù)干燥，設(shè)置同上。Dry per sub-batch. Mill the gr

36、anule to the fluid-bed bowl (container), install to GHIBLI-100 fluid- bed dryer. Push “l(fā)ift ”to tightly close the bowl with chamber. Set parameters as following: shake 2 seconds with the 60 seconds interval,inlet air temp. from *-*°C (target * °C ), blower 3000rpm, airflow 1500 2500m3/h (t

37、arget: *m 3/h), outlet air temp.from *-* C. When outlet air temp. leaps 2C or more, stop drying and pull out the bowl. Take 5g sample from centerwith sample thief refers to SOP-MD-099. Pass sample through 12 mesh and test moisture by mold style: 5, method:1, temperature:105 C . The moisture specific

38、ation is 1.5%-2.0%. Continue drying if moisture is out of specification. Set parameters as following : shake 2 seconds with the 30 seconds interval, inlet air temp. from 50-80 C (target 60 C ), blower 2500rpm , airflow 1000 1800m3/h (target *m 3/h), outlet air temp. from *-* C . sample the granulati

39、on and test the moisture. Continue cooling and repeat sample until the moisture is acceptable. The moisture specification is 1.5%-2.0%. Continue drying if moisture is out of specification with the parameters set as above mentioned.將每一料的干燥時(shí)間、進(jìn)風(fēng)風(fēng)量、進(jìn)風(fēng)溫度、物料溫度、出風(fēng)溫度和水分測(cè)試結(jié)果匯總于表2中。Collect the drying time, a

40、ir flow, inlet air temp., material temp., outlet air temp. and moisture test data in TABLE 2.表2沸騰干燥性能TABLE 2 FLUID BED DRYING DATA料次Sub-batch#批號(hào) Batch#:可接受標(biāo)準(zhǔn)Specification項(xiàng)目Item干燥時(shí)間Drying time(min)進(jìn)風(fēng)風(fēng)量Airflow(m3/h)進(jìn)風(fēng)溫度inlet airtemp. (C)物料溫度Materialtemp. (C)出風(fēng)溫度Outlet airtemp. (C)水分Moisture(%)1進(jìn)風(fēng)風(fēng)量2Ai

41、rflow :1500-23500m3/h;4目標(biāo)值target:5*m 3/h67進(jìn)風(fēng)溫度inlet86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共35頁(yè)第15頁(yè)8air9temp.:*-* °C ;10目標(biāo)值Target11* c1213出風(fēng)溫度Outlet14airtemp.:*-* C ;水分Moisture :1.5%-2.0%可接受標(biāo)準(zhǔn)依據(jù)86（Specification refer to :）制粒批生產(chǎn)記錄。manu facture record.檢驗(yàn)人 Analyzer

42、: 日期 Date: 復(fù)核人 Checked by: 日期 Date： 結(jié)論 Comments：&7干顆粒整粒 DRY MILLING將容器轉(zhuǎn)移到 YDF-120液壓提升機(jī)下，與提升機(jī)的錐蓋固定密封，啟動(dòng)提升機(jī)，進(jìn)行翻轉(zhuǎn)、提升等操作，將料桶就位，打開(kāi)容器閥門(mén)，開(kāi)啟回轉(zhuǎn)刀，經(jīng)不銹鋼圓形孔8目篩網(wǎng)整粒，設(shè)置轉(zhuǎn)速頻率 *-*hz（目標(biāo)值*hz ）。每料整粒后的干顆粒分別存放在不同的料桶中。在放料過(guò)程中，按開(kāi)始、中間、結(jié)束方法取約200克混樣，檢測(cè)水分，粒徑分布，性狀和異物，將檢驗(yàn)結(jié)果填寫(xiě)表3。每一料次放料結(jié)束后，使用標(biāo)準(zhǔn)溫度計(jì)分別測(cè)量第1, 7，14料次的物料溫度，將結(jié)果也填入表3。Clos

43、e the bowl with YDF-120 hydraulic lift miller tightly. Switch on the power, overturn the bowl, open container valve,start impeller to pass material through 8 mesh. Set impeller speed from *-*hz （target *hz）. Store milled granuleaccording to sub-batch#. During the milling, take samples from the begin

44、ning time, middle time, and ending time to form a 200g combined sample. Test and record in TABLE 3. After milling, test the material temp. of the 1: 7th, and14thsub-batches and record in TABLET 3.86 (300mg)工藝驗(yàn)證方案86 (300mg) PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382( P)共35頁(yè)第16頁(yè)0.3-0.7mm批號(hào)Batch#樣品號(hào)Samp

45、le ID取樣量Sample qty.檢測(cè)項(xiàng)目Test item檢測(cè)部門(mén)Tested by200g水分 Moisture、粒徑分布 Sieve test、 性狀 description> 異物檢測(cè) Foreign matter生產(chǎn)部中間控制MD In-process control物料溫度 Material temp.生產(chǎn)部中間控制MD In-process control批號(hào)Batch#:參數(shù)Result料 Sub-batch1234567可接受標(biāo)準(zhǔn)Specification12 目 mesh*布st20 目 mesh*te80 目 mesh*底盤(pán)Pan*粒徑分eSi ,總量Total

46、/性犬 Description*r< 0.3mm'k'k'ke查ttam*nigLT山總4入re異物檢of>0.7mm'k'k'k水分 Moisturet、t t 、，t b 2*x. c 'k'k'k'物料溫度Material temp. c料 Sub-batchy/可接受標(biāo)準(zhǔn)參數(shù) Result891011121314Specification12 目 mesh*布s te20 目 mesh*cc口*ev粒徑分80 曰 mesh 底盤(pán)Pan*ec總量 iotal/S性犬 Description'

47、;k'k'k查1 ig ett< 0.3mm表 3 干顆粒整粒TABLE 3 DRY MILLING DATA異ie aOFm*制藥廠(chǎng)* Factory86（ 300mg）工藝驗(yàn)證方案86 （300mg） PROCESS VALIDATIONPROTOCOL文件編號(hào)File#V-0382（ P）共35頁(yè)第17頁(yè)>0.7mm'k'k'k水分 Moisture'k'k'k物料溫度 Material temp. °C/可接受標(biāo)準(zhǔn)設(shè)定說(shuō)明Specification refer to :依據(jù)86制粒批生產(chǎn)記錄。manu

48、facture record.物料溫度檢查項(xiàng)目無(wú)可接受標(biāo)準(zhǔn)，結(jié)果僅作為數(shù)據(jù)積累。There is no specification for material temp., for it is the data accumulation,檢驗(yàn)人 Analyzer: 日期 Date: 復(fù)核人 Checked by: 日期 Date:結(jié)論 Comments：&8 總混 MIXING將外加的*kg、*kg分4次放入盛放干顆粒的容器中，做完整批10料顆粒經(jīng)安全篩網(wǎng)和磁力儀，全部進(jìn)入混合料斗中，加蓋，將料斗安放到HYD-2500自動(dòng)提升料斗混合機(jī)上，按動(dòng)上升鍵，使料斗固定，設(shè)定轉(zhuǎn)速為8轉(zhuǎn)/分鐘，混

49、合10分鐘出料，分裝在 3個(gè)600L周轉(zhuǎn)料車(chē)中，稱(chēng)量、顆粒進(jìn)中間庫(kù)復(fù)核驗(yàn)收。Totally add * and * into dry granule containers by 4 times. Pass 10 sub-batches through safety sieve and magnetic sieve into mixing tote. Cover, install into HYD-2500 mixer. Switch on power, securing the tote, and setting mixing speed at 8rpm. Mix for 10 minutes

50、. Discharge into 3 600L compression tote, weigh and transfer to in-process storage.混合程序結(jié)束后，由QA現(xiàn)場(chǎng)人員按示意圖位置和取樣方法在3個(gè)600L周轉(zhuǎn)料車(chē)中取樣，各取樣點(diǎn)均平行取樣3份（1份檢驗(yàn)、1份復(fù)測(cè)、1份留樣，樣品編號(hào)分別以A、B、C英文字母區(qū)分），正確填寫(xiě)取樣標(biāo)簽（名稱(chēng)、批號(hào)、取樣人、取樣時(shí)間和容器號(hào)等），送QC檢驗(yàn)水分、異物、性狀、含量、篩分試驗(yàn)和松密度。并將結(jié)果填寫(xiě)表4和表5。（為減小數(shù)據(jù)的差異性QC須在收到樣品后的一小時(shí)內(nèi)完成水分的檢測(cè)。）QA site personal sample parallel 3 times from each compression tote at sample locations （1 for te