產(chǎn)品年度質(zhì)量回顧分析報(bào)告固體制劑

1、產(chǎn)品年度質(zhì)量回顧分析報(bào)告Annual Product Review回顧日期：2009年01月2009年12月Date: Jan.2009 Dec. 2009品名Product Name左克（鹽酸左氧氟沙星膠囊）Levofloxacin Hydrochloride Capsule規(guī)格Specification0.1g生產(chǎn)車(chē)間Workshop 固體制劑二號(hào)車(chē)間No. 2 Solid Dosage Workshop制定人Drafted byQA：制定日期： 年 月 日Date:審核人Reviewed by車(chē)間主任：Workshop Manager:審核日期： 年 月 日Date:技術(shù)主管：Techn

2、ical supervisor:審核日期： 年 月 日Date:QA主管：QA Supervisor:審核日期： 年 月 日Date:批準(zhǔn)人Approved by質(zhì)管部部長(zhǎng)：Quality Assurance Manager:批準(zhǔn)日期： 年 月 日Date:6目 錄Content一、基本情況概述 . Overview 1. 產(chǎn)品年度質(zhì)量回顧目的 11. Proposal of Annual Product Review2. 2009年生產(chǎn)狀況:批次、數(shù)量，不合格批次、數(shù)量 12. Production Status of 2009: Batch and quantity; rejected b

3、atch and quantity3. 生產(chǎn)線狀況 13. Production line status二、生產(chǎn)和質(zhì)量控制情況分析評(píng)價(jià) . Analysis and evaluation of production and quality control1.產(chǎn)品生產(chǎn)過(guò)程質(zhì)量監(jiān)控要點(diǎn)監(jiān)控結(jié)果分析情況概述21. Analysis of in-process control result2.廠房設(shè)施設(shè)備維修、驗(yàn)證等情況概述72. Overview of facility, equipment maintenance and validation3.公用工程系統(tǒng)純化水、潔凈區(qū)空調(diào)系統(tǒng)檢測(cè)結(jié)果分析情況概

4、述83. Overview of testing result of purified water system and HVAC system for clean area4OOS調(diào)查處理情況 174. OOS investigation and handling5.偏差處理情況概述 175. Overview of deviation handling6.變更控制情況概述 176. Overview of change control7. 原料藥及使用包材的質(zhì)量回顧187. API and packaging material quality review8.中間體的質(zhì)量回顧 218. I

5、ntermediate quality review9.成品的質(zhì)量回顧 239. Finished product quality review10.穩(wěn)定性考察情況概述2610. Stability test overview11.驗(yàn)證情況概述2611. Validation overview12.向藥品監(jiān)管部門(mén)的申報(bào)及批準(zhǔn)情況概述2712. Review of cases applying to and approved by drug supervisory authority13.主要供應(yīng)商變化和供應(yīng)商審計(jì)情況2813. Main supplier change and supplier

6、 audit三、自檢情況、接受監(jiān)督檢查和抽檢情況28. Self-inspection, supervisory inspection and random inspection 四、補(bǔ)充申請(qǐng)28. Supplementary application五、產(chǎn)品不良反應(yīng)情況概述 29. ADR overview六、產(chǎn)品質(zhì)量投訴、退貨和產(chǎn)品召回29. Product quality complaint, return and recall七、結(jié)論. Conclusion1對(duì)產(chǎn)品質(zhì)量的評(píng)價(jià)301. Evaluation of product quality2存在問(wèn)題及改進(jìn)措施302. Problems

7、 and improvement measures3建議313. Suggestions附：附錄/ Appendices左克（鹽酸左氧氟沙星膠囊）2009年度質(zhì)量回顧分析報(bào)告Annual Product Review Report of Levofloxacin Hydrochloride Capsule, 2009一、基本情況概述：. Overview1 產(chǎn)品年度質(zhì)量回顧的目的Proposal of Annual product review產(chǎn)品年度質(zhì)量回顧是近年來(lái)藥品生產(chǎn)企業(yè)提高內(nèi)部審核能力、國(guó)家藥監(jiān)系統(tǒng)逐步強(qiáng)化的重點(diǎn)工作，根據(jù)2009年我公司建立并實(shí)施的產(chǎn)品年度質(zhì)量回顧標(biāo)準(zhǔn)操作規(guī)程，20

8、10年QA對(duì)固體制劑2號(hào)車(chē)間2009年全年生產(chǎn)的左克（鹽酸左氧氟沙星膠囊）進(jìn)行了年度質(zhì)量回顧分析。 APR is the key work which pharmacy manufacturing enterprises improve the inner auditing ability and state drug administrator system strengthens. Based on “SOP of Annual Product Review” established and implemented in 2009, QA have reviewed and analyze

9、d the quality of the levofloxacin hydrochloride produced by No. 2 Solid Dosage Workshop all through 2009 this year.22009年生產(chǎn)狀況：批次、數(shù)量，不合格批次、數(shù)量 2. Production status of 2009: Batch and quantity; rejected batch and quantity全年共生產(chǎn)左克（鹽酸左氧氟沙星膠囊）58批，其中12粒左克是53批，6粒左克5批，共出成品34432.85件，無(wú)不合格批次。We produce 58 batche

10、s of levofloxacin hydrochloride capsule, consisting of 53 batches of 12 grains and 5 batches of 6 grains, 34432.85 units in total with no rejected batch all the year round.3.生產(chǎn)線狀況3. Production line status該產(chǎn)品在集團(tuán)固體制劑2號(hào)車(chē)間生產(chǎn)，共設(shè)稱量、制粒、終混、充填、內(nèi)包裝、外包裝六個(gè)工序，主要生產(chǎn)設(shè)備有PMA600濕法混合制粒機(jī)、DFX600流化床干燥器、HZD2000自動(dòng)提升料斗混合機(jī)、SL

11、800干整機(jī)、MD2000料斗清洗機(jī)、GKF-2000膠囊充填機(jī)、UPS1040泡罩包裝機(jī)、C2304裝盒機(jī)、E3060裹包機(jī)、C6000大字符噴碼機(jī)等。2009年全年車(chē)間生產(chǎn)線各設(shè)備正常維護(hù)，未發(fā)生因設(shè)備故障導(dǎo)致的車(chē)間停產(chǎn)或成品報(bào)廢事件。This product is produced in No. 2 Solid Dosage Workshop with 6 procedures, that is, dispensing, granulation, final mixing, filling, primary packaging and secondary packaging. The m

12、ain equipments are PMA600 wet-mixing granulator, DFX600 fluid bed dryer, HZD2000 automatic blender with hopper lifting, SL800 dry calibration machine, MD2000 hopper cleaning machine, GKF-2000 capsule filling machine, UPS1040 blister packaging machine, C2304 box packaging machine, E3060 wrapping mach

13、ine, C6000 large character inkjet printing machine, etc. All the equipments of production line are maintained normally, with no production halts or finished product abandon led by equipment failure all the year.二、生產(chǎn)和質(zhì)量控制情況分析評(píng)價(jià). Analysis and evaluation of production and quality control1產(chǎn)品生產(chǎn)過(guò)程質(zhì)量監(jiān)控要點(diǎn)監(jiān)控

14、結(jié)果分析情況概述(產(chǎn)品生產(chǎn)過(guò)程質(zhì)量監(jiān)控要點(diǎn)監(jiān)控結(jié)果收集匯總表5415)1. Analysis of in-process control result (Collection form of in-process control result, 5415)（1）監(jiān)控項(xiàng)目：產(chǎn)品制粒過(guò)程控制(1) Monitored items: granulation process control制粒granulation監(jiān)控點(diǎn)monitoring point粘合劑用量adhesive dosage (kg)攪拌速度stirring rate (rpm)切碎攪拌時(shí)間cutting & stirring tim

15、e（min）物料溫度material temp.()顆粒水分LOD of granule（%）中心傾向數(shù)據(jù)central tendency data平均值average value43.64150.008.0067.842.60中位數(shù)median42.001508.0067.802.60樣本眾數(shù)sample mode42.001508.0067.802.60離散程度數(shù)據(jù)dispersion degree data極差range9.400.000.003.201.80最小值minimum value41.00150.008.0066.501.60最大值maximun value50.40150.

16、008.0069.703.40RSD8.48%0.00%0.00%0.84%15.04%計(jì)數(shù)total58批58 batches評(píng)價(jià)：對(duì)09年全年左克膠囊生產(chǎn)過(guò)程質(zhì)量監(jiān)控點(diǎn)中粘合劑用量、攪拌時(shí)間、攪拌速度、切碎時(shí)間、物料溫度、顆粒水分進(jìn)行分析，通過(guò)以上折線圖顯示及統(tǒng)計(jì)數(shù)據(jù)看，粘合劑用量、攪拌時(shí)間、攪拌速度、切碎時(shí)間、物料溫度中心傾向數(shù)據(jù)與標(biāo)準(zhǔn)中心較為接近，整體離散程度數(shù)據(jù)呈現(xiàn)出波動(dòng)較小，但中間產(chǎn)品顆粒水分控制離散程度較大，車(chē)間在顆粒水分控制方面有待采取措施進(jìn)一步改善。Evaluation: For the granulation process, we focus on analysing a

17、dhesive dosage, stirring time, stirring rate, cutting time, material temperature and LOD of granule. By the line graphs and the statistics under related items, central tendency data of adhesive dosage, stirring time, stirring rate, cutting time, material temperature is approximate to standard centra

18、l, and the data of whole dispersion degree fluctuates a little. However, dispersion degree of granule LOD is much higher, which means the workshop shall take further step to control the moisture.（2）監(jiān)控項(xiàng)目：膠囊充填過(guò)程控制(2) Monitoring item: capsule filling control充填filling監(jiān)控點(diǎn)monitoring item理論裝量theoretical fi

19、ll mass實(shí)際裝量actual fill mass理論裝量上限maximum theoretical fill mass理論裝量下限minimum theoretical fill mass中心傾向數(shù)據(jù)central tendency data平均值average value0.2220.2220.2390.205中位數(shù)median0.2220.2220.2390.205樣本眾數(shù)sample mode0.2212389380.2210.2378318580.204646018離散程度數(shù)據(jù)dispersion degree data極差range0.0059269790.0060.00637

20、15030.005482456最小值minimum value0.2192982460.2190.2357456140.202850877最大值maximum value0.2252252250.2250.2421171170.208333333RSD（%）0.60%0.64%0.60%0.60%計(jì)數(shù)total58批58 batches評(píng)價(jià)：通過(guò)以上折線圖顯示及相應(yīng)參數(shù)項(xiàng)下的數(shù)據(jù)統(tǒng)計(jì)分析，中間傾向數(shù)據(jù)與標(biāo)準(zhǔn)中心較為接近，整體離散程度數(shù)據(jù)呈現(xiàn)出波動(dòng)較小，證明鹽酸左氧氟沙星膠囊在充填過(guò)程中裝量比較穩(wěn)定。Evaluation:By analysing the line graph and the s

21、tatistics under related items, central tendency data is approximate to standard central, and the data of whole dispersion degree fluctuates a little, which proves that the fill mass in filling process is stable.充填filling監(jiān)控點(diǎn)monitoring item充填速度f(wàn)illing rate中心傾向數(shù)據(jù)central tendency data平均值average value12.

22、7中位數(shù)median13.0樣本眾數(shù)sample mode13離散程度數(shù)據(jù)dispersion degree data極差range1.0最小值minimum value12.0最大值maximum value13.0RSD（%）3.10%計(jì)數(shù) total58批58 batches評(píng)價(jià)：通過(guò)以上折線圖顯示及相應(yīng)參數(shù)項(xiàng)下的數(shù)據(jù)統(tǒng)計(jì)分析，中間傾向數(shù)據(jù)與標(biāo)準(zhǔn)中心較為接近，整體離散程度數(shù)據(jù)呈現(xiàn)出波動(dòng)較小，證明在鹽酸左氧氟沙星膠囊充填過(guò)程中充填速度能保證產(chǎn)品質(zhì)量穩(wěn)定。Evaluation:By analysing the line graph and the statistics under relat

23、ed items, central tendency data is approximate to standard central, and the data of whole dispersion degree fluctuates a little, which proves that the filling rate can ensure product quality stability.評(píng)價(jià)：從2009年全年0.1g左克膠囊產(chǎn)品的生產(chǎn)過(guò)程質(zhì)量監(jiān)控要點(diǎn)數(shù)據(jù)，表明該產(chǎn)品全年生產(chǎn)情況較為穩(wěn)定，各批次生產(chǎn)過(guò)程質(zhì)量監(jiān)控點(diǎn)均嚴(yán)格控制在規(guī)定工藝參數(shù)范圍內(nèi)，從而保證了中間產(chǎn)品、成品數(shù)據(jù)趨于穩(wěn)定，波

24、動(dòng)范圍小，表明我車(chē)間左克膠囊過(guò)程質(zhì)量監(jiān)控點(diǎn)設(shè)置合理、控制穩(wěn)定，對(duì)異常因素能及時(shí)加以消除，確保產(chǎn)品工藝過(guò)程能始終如一地生產(chǎn)出均一穩(wěn)定的產(chǎn)品，充分滿足了市場(chǎng)和廣大患者的需求。Evaluation: The in-process control data of levofloxacin hydrochloride capsule (0.1g) suggests that the production goes stably all the year. The in-process quality monitoring points of all the batches are controlled

25、strictly in the range of the regulated process parameter, which ensures that the data of intermediates and finished products tends to be stable and fluctuates a little. And it also suggests that the in-process monitoring point is reasonable, the control is stable and the abnormal factors can be elim

26、inated in time, which ensures the stable production and meets the requirements of the market and the patients.2.廠房設(shè)施設(shè)備維修、校驗(yàn)、驗(yàn)證等情況概述2. Overview of facility & equipment maintenance, calibration and validation（1）設(shè)備維護(hù)、維修情況概述（關(guān)鍵設(shè)備維護(hù)維修情況數(shù)據(jù)匯總5418）（1） Equipment maintenance and repair (Data collection of cri

27、tical equipment maintenance and repair 5418)全年左克膠囊生產(chǎn)使用的關(guān)鍵設(shè)備維護(hù)維修過(guò)程嚴(yán)格按照“設(shè)備維修管理規(guī)程”要求進(jìn)行維修和驗(yàn)收，全年共檢查維修18次，主要集中在設(shè)備密封損壞或軸承損壞，通過(guò)及時(shí)的維護(hù)檢修，確保設(shè)備運(yùn)行狀態(tài)完好。The procedure of critical equipment maintenance and repair all through the year strictly follows “SMP of Equipment Maintenance”. The equipments have been checked

28、and repaired for 18 times all the year, mainly including seal damage or bearing failure. By timely maintenance the equipments are guaranteed to run well.（2）設(shè)備校驗(yàn)情況概述(設(shè)備校驗(yàn)情況匯總表5419)（2）Equipment calibration (Collection form of equipment calibration 5419)本年度對(duì)PMA600型濕法混合制粒機(jī)、DFX600型流化床干燥器、C&C100型膠囊分造拋光機(jī)、Y

29、J-150型膠囊燈檢機(jī)、UPS1040型泡罩機(jī)、S1型自動(dòng)檢重秤、C2304型裝盒機(jī)、CF-20T型開(kāi)箱機(jī)、MH-FJ-3A型封箱機(jī)上壓力表及壓差表及時(shí)進(jìn)行了校驗(yàn)，確保儀器儀表符合生產(chǎn)要求。The pressure gauge and differential pressure gauge of wet-mixing granulator, DFX600 fluid bed dryer, C&C100 Capsule Polisher, YJ-150 capsule visual inspection machine, UPS1040 blister packaging machine, S1

30、 automatic checkweigher, C2304 wrapping machine, CF-20T carton unpacking machine and MH-FJ-3A carton sealer are calibrated timely this year to ensure that the instruments and meters meet the production requirements.（3）設(shè)備驗(yàn)證概述（設(shè)備驗(yàn)證情況匯總表5420）（3） Equipment validation overview (Collection form of equipme

31、nt validation 5420)濕法混合制粒機(jī)、噴霧干燥器、自動(dòng)提升料斗混合機(jī)、膠囊充填機(jī)、料斗清洗機(jī)、泡罩機(jī)、裝盒機(jī)、裹包機(jī)等設(shè)備均進(jìn)行了定期再驗(yàn)證，驗(yàn)證評(píng)價(jià)是設(shè)備運(yùn)行良好，符合生產(chǎn)要求。Wet-mixing granulator, spray dryer, automatic blender with hopper lifting, capsule filling machine, hopper cleaning machine, blister packaging machine, wrapping machine are revalidated and the evaluatio

32、n is that the equipments run well and meet production requirements.評(píng)價(jià)：全年進(jìn)行的維修、保養(yǎng)活動(dòng)主要目的在于排除日常隱患，使產(chǎn)品質(zhì)量隱患消除于事發(fā)前，使設(shè)備零部件得到一個(gè)良好的清潔、潤(rùn)滑、維護(hù)保養(yǎng)，并發(fā)揮最大作用。通過(guò)全年各生產(chǎn)設(shè)備按時(shí)維護(hù)保養(yǎng)，維修及時(shí)，沒(méi)出現(xiàn)一起因設(shè)備導(dǎo)致的產(chǎn)品質(zhì)量及停產(chǎn)事件，表明全年所進(jìn)行的維修活動(dòng)充分體現(xiàn)了固體制劑2號(hào)車(chē)間設(shè)備管理以提前預(yù)防為主的理念，從而為生產(chǎn)操作人員確保生產(chǎn)過(guò)程的穩(wěn)定可靠打下了堅(jiān)實(shí)的基礎(chǔ)。Evaluation: The main purpose of repair and maint

33、enance all over the year is to eliminate daily hidden danger and quality hidden danger, and to clean, lubricate and maintain equipment components in order to perform better. Because of the timely maintenance and repair, no quality events or production halts happened caused by equipment failure, whic

34、h suggests that the year-round maintenance shows “prevention first” in No. 2 Solid Dosage Workshop and lays a strong foundation for the production stability.3.公用工程系統(tǒng)純化水、潔凈區(qū)空調(diào)系統(tǒng)檢測(cè)結(jié)果分析情況概述：3. Overview of testing result of purified water system and HVAC system for clean area（1）純化水(工藝用水檢驗(yàn)結(jié)果匯總表5428) (1)

35、Purified water (Collection form of process water testing results 5428)評(píng)價(jià)：2009年固體制劑2號(hào)車(chē)間左克膠囊產(chǎn)品生產(chǎn)使用的純化水系統(tǒng)總出水口、總回水口各項(xiàng)檢測(cè)指標(biāo)均符合中國(guó)藥典2005版要求。滿足產(chǎn)品生產(chǎn)需求。Evaluation: All testing results of main outlet-water and main backwater of purified water system for Zuoke capsule production in No. 2 Solid Dosage Workshop in

36、 2009 meet the requirements of Chinese Pharmacopoeia 2005 and meet the production requirements.（2）潔凈區(qū)(固體制劑2號(hào)車(chē)間潔凈區(qū)空調(diào)系統(tǒng)監(jiān)測(cè)結(jié)果匯總表5429)（2）Clean area (Collection form of HVAC system monitoring results of clean area in No. 2 Solid Dosage Workshop 5429)監(jiān)控項(xiàng)目1：沉降菌（法定標(biāo)準(zhǔn)10個(gè)）、浮游菌（法定標(biāo)準(zhǔn)500CFU/m3）Monitoring item1: a

37、irborne particles ( 10), airborne microbe ( 500CFU/m3)（2）潔凈區(qū)(固體制劑2號(hào)車(chē)間潔凈區(qū)空調(diào)系統(tǒng)監(jiān)測(cè)結(jié)果匯總表5429)監(jiān)控項(xiàng)目2：塵埃粒子（0.5um粒子3520000粒/m3, 5um粒子29000粒/m3 ）Monitoring item2: dust particles ( 0.5m particle 3520000 grains/m3, 5m particle29000 grains/m3 ）評(píng)價(jià)： 2009年QC對(duì)固體制劑2號(hào)車(chē)間各潔凈區(qū)的空調(diào)系統(tǒng)及環(huán)境都定期進(jìn)行了監(jiān)測(cè)，對(duì)塵埃粒子數(shù)檢測(cè)結(jié)果統(tǒng)計(jì)分析，0.5um粒子限度不得過(guò)3

38、520000粒/m3, 5um粒子不得過(guò)29000粒/m3，實(shí)際測(cè)試數(shù)據(jù)均遠(yuǎn)遠(yuǎn)低于規(guī)定限度,塵埃粒子檢測(cè)結(jié)果均符合EU GMP要求; 對(duì)全年的沉降菌及浮游菌按規(guī)定周期檢測(cè)的數(shù)據(jù)分析，結(jié)果均符合法定標(biāo)準(zhǔn)且波動(dòng)較小。表明車(chē)間潔凈區(qū)環(huán)境得到有效的保證，證明該產(chǎn)品是在空調(diào)系統(tǒng)完好，環(huán)境受控的狀態(tài)下生產(chǎn)的。Evaluation: In 2009, QC has periodically monitored the HVAC system and environment in all clean area of No. 2 Solid Dosage Workshop and tested the dust

39、 particle testing result as the limit of 0.5um particle should be no more than 3520000 grains/ m3 and 5um particle should be no more than 29000 grains/ m3. Practical data is far less than the regulated limit and the dust particle testing results all meet the EU GMP requirements; we analyze the data

40、of airborne particles and airbornemicrobe, which obtained from QC periodical testing, the results conform to official standard and fluctuate slightly. We can infer that the environment of clean area are ensured and proves that the capsule is produced under good HVAC system and controlled environment

41、.4OOS調(diào)查處理情況4. OOS Investigation and Handling（1）中間體(中間產(chǎn)品檢驗(yàn)OOS情況匯總表5413)(1) Intermediates (Collection form of intermediates testing OOS 5413)（2）成品(檢驗(yàn)OOS情況匯總5426) (2) Finished Products (Collection form of finished product testing OOS 5426)對(duì)該產(chǎn)品OOS調(diào)查處理情況進(jìn)行排查，2009年全年左克膠囊產(chǎn)品生產(chǎn)沒(méi)出現(xiàn)一起中間產(chǎn)品檢驗(yàn)OOS偏差，成品也沒(méi)有發(fā)生一起檢驗(yàn)OOS

42、。全部合格后放行。No OOS results occurred in testing of intermediates or finished products all over the year 2009. The products were all released.評(píng)價(jià)：表明左克膠囊產(chǎn)品生產(chǎn)條件成熟，工藝穩(wěn)定，產(chǎn)品質(zhì)量能得到有效保證。Evaluation: It suggests that the production condition of Zuoke capsule is mature, the process is stable, and the quality is guar

43、anteed.5偏差處理情況概述（偏差及偏差處理情況匯總5416）5. Overview of deviation handling (Collection form of deviation and deviation handling 5416)09年全年左克（鹽酸左氧氟沙星膠囊）生產(chǎn)過(guò)程中沒(méi)發(fā)生一起偏差。No deviation during Zuoke (levofloxacin hydrochloride capsule) production has happened all over 2009.評(píng)價(jià)：09年全年左克（鹽酸左氧氟沙星膠囊）生產(chǎn)過(guò)程中無(wú)一起因介質(zhì)、人員、物料、環(huán)境等因

44、素造成的偏差情況發(fā)生。表明固體制劑2號(hào)車(chē)間質(zhì)量保障體系完善，左克膠囊產(chǎn)品生產(chǎn)工藝成熟，過(guò)程穩(wěn)定，產(chǎn)品質(zhì)量能得到有效保證。Evaluation: No deviation during Zuoke (levofloxacin hydrochloride capsule) production has happened all over 2009, which suggests that the quality assurance system of No. 2 Solid Dosage Workshop is complete, the process is mature and the pro

45、duction is stable, based on which the quality can be guaranteed.6變更控制情況概述（變更控制實(shí)施情況匯總表5434）6. Overview of change control (Collection form of change control implementation 5434)全年共進(jìn)行與廠房設(shè)施設(shè)備相關(guān)的變更共4次：There have been 4 changes on facility and equipment in 2009:1 BG2009066和BG2009148:對(duì)潔凈區(qū)部分房間及純化水循環(huán)管路使用點(diǎn)變更，

46、變更后對(duì)空調(diào)系統(tǒng)及水系統(tǒng)重新進(jìn)行了驗(yàn)證，驗(yàn)證合格后投入使用。 BG2009066 & BG2009148: Some rooms in clean area and using points of purified water circulation pipeline were changed. After successful validations of HVAC system and Water system, they came into use.2 BG2009194：新增烏爾曼包裝線，增加設(shè)備模具存放間，將現(xiàn)有與模具間相鄰的1217器具晾干間變更為1217模具間。 BG200919

47、4: Add Moulds Storage Room for the new Uhlmann packaging line, i.e. change Drying Tools Room 1217 next to a Moulds Storage Room into Moulds Storage Room 1217.3 BG2009195：因擴(kuò)大產(chǎn)能及歐盟CGMP項(xiàng)目認(rèn)證，新增純化水使用點(diǎn)CYD125并在其后端安裝了一套用于生產(chǎn)設(shè)備清洗用的WIP站，并對(duì)整個(gè)水系統(tǒng)進(jìn)行認(rèn)證。 BG2009195: To expand capacity and for EU GMP certification, a

48、dd a new using point CYD125 in purified water system and install a WIP system behind it. Water system was validated before put into use.4 BG2009340：變更車(chē)間風(fēng)冷臭氧發(fā)生器為水冷臭氧發(fā)生器,變更后對(duì)該臭氧發(fā)生系統(tǒng)進(jìn)行了驗(yàn)證,驗(yàn)證合格后投入使用。 BG2009340：Air-cooled ozonator was changed into water-cooled ozonator. After a successful validation, it

49、came into use.評(píng)價(jià)：全年提出變更均已順利、如期完成，廠房設(shè)施維護(hù)正常，保證了產(chǎn)品質(zhì)量穩(wěn)定。Evaluation: Change plan in 2009 have been conducted smoothly on time and facility maintenance goes well, which ensure stable product quality.7原料藥及使用包材的質(zhì)量回顧7. API and packaging material quality review（1）產(chǎn)品原輔料檢驗(yàn)數(shù)據(jù)收集匯總5421： (1) Testing data collection

50、 form of API & Excipients 5421:全年左克生產(chǎn)共使用鹽酸左氧氟沙星原料（口服用）20批，分別由浙江普洛康裕、浙江司太立兩家提供，原料批次及關(guān)鍵質(zhì)量指標(biāo)分析如下：Twenty batches of levofloxacin hydrochloride API (for oral medicine) are used in 2009, supplied by Zhejiang Apeloa Pharmaceutical Company and Zhejiang Starry Pharmaceutical Company respectively. API batch a

51、nd critical quality criteria are analyzed as follows:鹽酸左氧氟沙星原料（口服用）levofloxacin hydrochloride (for oral medicine)監(jiān)控點(diǎn)monitoring point浙江普洛康裕Apeloa, Zhejiang 浙江司太立Starry, Zhejiang水分%Moisture%含量%Content%水分%Moisture%含量%Content%中心傾向數(shù)據(jù)平均值A(chǔ)verage value4.389.883333334.489.96428571中位數(shù)median4.389.84.390樣本眾數(shù)Sam

52、ple mode#N/A90.24.389.8離散程度數(shù)據(jù)極差range0.60.60.80.5最小值Minimum value489.6489.7最大值Maximum value4.690.24.890.2RSD（%）0.0550330.00285090.06818180.00222評(píng)價(jià)：通過(guò)以上折線圖顯示及相應(yīng)參數(shù)項(xiàng)下的數(shù)據(jù)統(tǒng)計(jì)分析，中間傾向數(shù)據(jù)與標(biāo)準(zhǔn)中心較為接近，整體離散程度數(shù)據(jù)呈現(xiàn)出波動(dòng)較小，證明鹽酸左氧氟沙星（供口服用）原料檢驗(yàn)結(jié)果符合企業(yè)質(zhì)量控制標(biāo)準(zhǔn)，從源頭上使產(chǎn)品質(zhì)量得到可靠的保證。浙江普洛康裕及浙江司太立兩家提供的原料質(zhì)量比較而言浙江司太立的水分整體離散程度略有波動(dòng)。該廠家原料

53、質(zhì)量可以進(jìn)一步改善。Evaluation: By analysing the line graph and the statistics under related items, central tendency data is approximate to standard central, and the data of whole dispersion degree fluctuates a little, which proves the testing result of levofloxacin hydrochloride (for oral medicine) meets the

54、 quality control standard, and guarantees the quality from the beginning. Comparing the API quality of Zhejing Apeploa and Zhejing Starry, the moisture dispersion degree of Zhejiang Starry fluctuates a little, which shall be improved.（2）原輔料和包裝標(biāo)簽使用異常情況匯總表5430(2) Collection form of API & excipients an

55、d packaging label abnormal using 5430全年左克膠囊產(chǎn)品使用的原輔料和包裝標(biāo)簽使用未發(fā)生任何異常。No abnormal using of API & excipients and packaging label happens this year.評(píng)價(jià)：表明09年全年固體制劑2號(hào)車(chē)間左克膠囊產(chǎn)品使用的原輔料和包裝標(biāo)簽，供應(yīng)商提供物料質(zhì)量穩(wěn)定，且保持相對(duì)固定，滿足生產(chǎn)需求；Evaluation: It suggests that the quality of API & excipients and packaging label used for levofloxacin hydrochloride