【正文】 The shape of rail is irregular, so it39。There is gap here, which allows chemical active ingredients to stay.取樣口取樣點(diǎn)：sampling point on sampling port 干式整粒機(jī) SL600 dry type straightening granulator編號：16Serial 取樣位置Sampling locations選擇原因Reasons 29 / 41干式整粒機(jī)出料口，清洗水中的化學(xué)活性殘留物容易殘積Discharge port of dry type straightening granulator is a location allows chemical active ingredients to stay easily.干整機(jī)出料閥取樣點(diǎn)：sampling point on discharge valve編號：17Serial 取樣位置Sampling locations選擇原因Reasons 篩網(wǎng)遍布小孔，容易殘積化學(xué)活性成分There are many meshes on the screen, which allows chemical active ingredients to stay easily.篩網(wǎng)取樣點(diǎn)：sampling point on screen編號：18Serial 取樣位置Sampling locations選擇原因Reasons SL600 干式整粒機(jī)通過手工清洗，此處手工清洗難度大，清洗效果相對差SL600 dry type straightening granulator is washed manually,. This part is hard to be cleaned by hand. Cleaning effect is not very good.整粒機(jī)上內(nèi)壁取樣點(diǎn)：sampling point on inner surface 自動(dòng)提升料斗混合機(jī)（400L）HZD800 Automatic Lifting Hopper Mixer（400L）編號：19Serial 取樣位置Sampling locations選擇原因Reasons 30 / 41此處為料斗上內(nèi)壁，清潔難度大This point is on inner surface of hopper, which is hard to clean.料斗上內(nèi)壁取樣點(diǎn)：sampling point on inner surface of hopper編號：20Serial 取樣位置Sampling locations選擇原因Reasons 由于此取樣的位置在最下面，各種殘留物容易在此積聚。s easy for chemical active ingredients to stay on.上筒內(nèi)壁進(jìn)料口取樣點(diǎn)： sampling point of feeding port on inner wall of upper cylinder編號：12Serial 取樣位置Sampling locations選擇原因Reasons 物料在干燥過程中與物料鍋壁充分接觸，上筒壁觀察窗邊緣面不規(guī)則，邊角處易殘留化學(xué)活性成分。再取一根用取樣溶液潤濕并已擠去多余溶液的聚酯纖維棉簽在與前次擦拭移動(dòng)方向垂直的方向上按同法擦拭取樣。目檢合格后按順序在取樣位置上先進(jìn)行微生物取樣，再進(jìn)行化學(xué)殘留取樣，微生物取樣及化學(xué)殘留留取樣位置不能重復(fù)，其中微生物取樣面積為 25cm 化學(xué)殘留取樣面積為 25cm 2。 no “√” means product has no direct contact with equipment involved21 / 41 (擦拭法 swab test)產(chǎn)品Product最 大 允 許 殘 留 總 量MAR[mg]設(shè) 備 面 積 cm2 單 位 面 積 殘 留 限 度181。There should be no residual after visual check after equipment cleaning according to the related SOP. If the ethanol is used for cleaning, visual check after half hour to ensure there’s no residual on the surface of the equipment.2 化學(xué)殘留可接受標(biāo)準(zhǔn)的確定 Calculation of Maximum Acceptance Residue （MAR）（1）1/1000 原則：下一產(chǎn)品的最大日劑量中含有的上一產(chǎn)品殘留物不得多于上一產(chǎn)品最低有效量的千分之一。Conclusion：Through the analysis of the above table, the worst case product are Product A, E and F.13 / 41五 驗(yàn)證方案表格 Validation matrix 產(chǎn)品 EProduct E驗(yàn)證方案Validation protocol序號Serial No.設(shè)備名稱Equipment name產(chǎn)品 AProduct A 搖擺oscillating聯(lián)機(jī)Linkup產(chǎn)品 FProduct F按設(shè)備驗(yàn)證（此設(shè)備上所要驗(yàn)證的產(chǎn)品數(shù)）(equipmentspecific): Number of products to be validated1 GHJ50 高效混和機(jī)High Efficient Mixer √ √ 12PMA400 濕法制粒機(jī)（不含篩網(wǎng)）Wet Type Granulator(excluding screen) √ √ 23 PMA400 濕法制粒機(jī)（含篩網(wǎng)）Wet Type Granulator(including screen)√ √ 24 DFX400 流化床干燥器DFX 400 fluid bed dryer √ √ √ √ 35 GEA 聯(lián)機(jī)管道GEA linkup pipes √ √ 26SL600 干式整粒機(jī)（不含篩網(wǎng)）SL600 dry type straightening granulator(excluding screen) √ √ 27SL600 干式整粒機(jī)（1150μm 篩網(wǎng)）SL600 dry type straightening granulator( 1150μm screen)√ 18SL600 干式整粒機(jī)（1350μm 篩網(wǎng)）SL600 dry type straightening granulator( 1350μm screen) √ 19HZD800 自動(dòng)提升料斗混合機(jī)800L)HZD800 Automatic Lifting Hopper Mixer 800L √ √ 210HZD800 自動(dòng)提升料斗混合機(jī)(400L)HZD800 Automatic Lifting Hopper Mixer 400L√ √ 211HZD800 自動(dòng)提升料斗混合機(jī)(200L)HZD800 Automatic Lifting Hopper Mixer 200L√ 112S250/40EUB 壓片機(jī)（）S250/40EUB Tablet Press（） √ √ 113S250/40EUB 壓片機(jī)（8mm）S250/40EUB Tablet Press（8mm）√ 114 / 4114 UPS1030MTI 鋁塑包裝機(jī) thermoforming machine √ √ √ √ 315 剝藥機(jī)Deblistering machine √ √ √ √ 316 YK160A 搖擺顆粒機(jī)oscillating granulator √ √ 217 CTCⅡ熱風(fēng)循環(huán)烘箱circulating hot air oven 18 ZS650 型漩渦振蕩篩Eddy type oscillating screen 19 LSH220 型濕法造粒機(jī)Wet type granulator 20 HLSG10 濕法混合制粒機(jī)Wet type mixing granulator 21 FL5 沸騰制粒機(jī)Fluid bed dryer 22GFK2022 膠囊充填機(jī)Gelatine Capsule Filling and Closing Machine √ 123 DXDP350 雙鋁遮光包裝機(jī)Double aluminum packaging machine 244S1000 四封小袋包裝機(jī)Automatic Packaging Machine For Singledose Sachet 25 BGB10C 包衣機(jī)Coating machine 26 GSHP150F 包衣機(jī)Coating machine √ 127 FL350 風(fēng)冷式粉碎機(jī)Cooling air crusher √ 128 稱量設(shè)備Weighing facility 29 周轉(zhuǎn)桶 AContainer type A 30 周轉(zhuǎn)桶 BContainer type B 驗(yàn)證方案 Validation protocol 按產(chǎn)品：所涉及的設(shè)備(productspecific): Number of production equipment items 10 9 9 9由上表數(shù)據(jù)，對三個(gè)最壞產(chǎn)品做連續(xù)三批的清潔驗(yàn)證。Conclusion: According to the group (see above table), product D and I has no risk in the aspect of solubility, therapeutic dose, color and flavour, they are defined as the no risk product in the cleaning validation10 / 41Product產(chǎn)品 溶解性組Solubility risk group Active pharmaceutical ingredient is practically insoluble 活性成分不溶于水藥理學(xué)Pharmacologyrisk group Therapeutic dose is 100mg 治療劑量100mg（此處也可以 MTDD 計(jì)算）活性成分含量Content of activepharmaceuticalingredient處方風(fēng)險(xiǎn)組Formulation risk group Product contains dye, flavours or other ponents that are difficult to remove 產(chǎn)品含有顏色，氣味或其他難容的成分A 幾乎不溶于水 500mg 50% B 溶于水 50 25% C 不溶于水 200 20% 處方中有 2%的染料2% dye in the formulation E 幾乎不溶于水 10 5% F 溶于水 75 50% G 溶于水 150 50% 包衣層中有 1%的顏料1% pigment in film coating H 幾乎不溶于水 150 30% 11 / 41分組選擇最壞情況 Worst case product choosen按活性成分溶解性，治療劑量和處方（顏色，氣味，難溶成分）分組，在每個(gè)分組中再按溶解性最差，治療劑量最低和活性成分含量最高的原則選出最壞情況產(chǎn)品Group all the products according to solubility, therapeutic dose, formulation (colour, flavour, ponents that are difficult to remove), in each group, choose the products with worst solubility, lowest therap. Dose and highest content of API, defined these products as the worst case products產(chǎn)品Product 活性成分含量Content of active pharmaceuticalin gredient 溶解性Solubility 治療劑量 （MTDD） 最壞情況Worst case 溶解性組 Solubility risk group A 50 % 幾乎不溶于水practically ins