【正文】 s是YesQA 人員取樣錯(cuò)誤Wrong samples are taken by QA.不能得到準(zhǔn)確的檢測(cè)結(jié)果Inaccurate testing result高High在清潔驗(yàn)證方案中對(duì)取樣點(diǎn)進(jìn)行編號(hào)并用圖片的方式進(jìn)行標(biāo)識(shí)。Sampling locations should be numbered and indicated with pictures in the cleaning validation protocol 是Yes是Yes8 / 41檢測(cè)人員對(duì)殘留物檢測(cè)方法不熟悉Testers are not familiar with testing methods of residue. 不能得到準(zhǔn)確的檢測(cè)結(jié)果，清潔評(píng)估失敗Inaccurate testing result。 cleaning evaluation fails中medium對(duì)參加樣品檢測(cè)的分析人員進(jìn)行《清潔驗(yàn)證分析方法驗(yàn)證方案》和《微生物驗(yàn)證方案》培訓(xùn)考核。Analyzers involved in testing samples should be trained and assessed for Validation Protocol of Analytical Method in Cleaning Validation and Microbial Validation Protocol.是Yes是Yes人員衛(wèi)生不符合要求Personnel hygiene doesn39。t meet requirements.微生物污染Microbial contamination低low培訓(xùn)衛(wèi)生管理相關(guān) SOPPersonnel should be trained for related SOP for hygiene management.是Yes是Yes9 / 412 最壞情況產(chǎn)品選擇 Worst case product Selection將產(chǎn)品按活性成分溶解性，治療劑量，處方（顏色，氣味，難溶成分）進(jìn)行分組，首先挑選出無風(fēng)險(xiǎn)的產(chǎn)品。Group all the products according to solubility, therapeutic dose, formulation (colour, flavour, ponents that are difficult to remove), pick up the no risk products first. 產(chǎn)品風(fēng)險(xiǎn)確定表格 Assignment of products to risk groups 產(chǎn)品 Product溶解性組Solubility risk group Active pharmaceutical ingredient is practically insoluble API 成分不溶于水藥理學(xué)組Pharmacology risk group Therapeutic dose is 100mg 治療劑量100mg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，氣味或其他難溶的成分無風(fēng)險(xiǎn)組 No risk A √ B √ C √ √ D √E √ √ F √ G √ H √ I √備注：實(shí)際操作中，選擇低于所有產(chǎn)品治療劑量范圍的第三小的那個(gè)。Note: In practice, a value is remended that is within the lower third of the available dosing range with respect to the entire product range. 結(jié)論：由以上分組可知，產(chǎn)品 D 和產(chǎn)品 I 在溶解性，治療劑量和顏色氣味等方面均無風(fēng)險(xiǎn)，歸為無風(fēng)險(xiǎn)組。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 insoluble 500 mg 活性成分含量最高Content of active pharmaceutical ingredient, is the highest in this groupC 20 % 不溶于水insoluble 200 mg E 5 % 幾乎不溶于水practically insoluble 10 mg 治療劑量最低therap. dose H 30 % 幾乎不溶于水practically insoluble 150 mg 此組選擇產(chǎn)品 A 和 E Choose product A and E in this group藥理組 Pharmacology risk group B 25 % 溶于水soluble 50 mg E 5 % 幾乎不溶于水practically insoluble 10 mg 溶解性最差Solubility, therap. dose F 50 % 溶于水Soluble 75 mg 活性成分含量最高Content of active pharmaceutical ingredient 此組選擇產(chǎn)品 E 和 F12 / 41Choose product E and F in this group處方風(fēng)險(xiǎn)組 Formulation risk group C 處方中有 2%的染料2% dye in the formulation 溶解性染料Soluble dye . 染料 Dye G 包衣層中有 1%的顏料1% pigment in film coating不溶解顏料Insoluble pigment . 顏料 Pigment 對(duì)于 C 產(chǎn)品，其處方中有 2%的可溶性染料，雖然不是活性成分，但也會(huì)對(duì)后續(xù)產(chǎn)品產(chǎn)生交叉污染。在此我們采取目視方法，用白色濕抹布在設(shè)備關(guān)鍵部位擦拭，肉眼分辨其是否有顏色。 對(duì)于 G 產(chǎn)品，其包衣層中有不溶解的顏料，所以只針對(duì)包衣機(jī)做目檢，方法是用干抹布擦拭設(shè)備表面看，肉眼分辨否有顏色殘留。 For product C, there is 2% dye in the it’s formulation, the dye is not the API, but still will affect the subsequent product, increase the risk of croscontamination. The visually check is used for it. We use the clean wet white tower scrub in the critical part of the equipment, see if the color is on the tower. For product G, the insoluble pigment is in the coating formulation, the visual check method is taken only for the coating machine. We use the clean white dry tower to scrub the scrub in the critical part of the equipment see if the color is on the tower.結(jié)論： 通過上表的分析，所選取的最壞情況產(chǎn)品為 A，E 和 F。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(hào)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√ √ 211HZ