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| column | value |
|---|---|
| 類別 | 查驗登記類,藥品查驗登記審查準則,疫苗類藥品之查驗登記 |
| 法規性質 | 法規命令 |
| 法規名稱 | 藥品查驗登記審查準則－疫苗類藥品之查驗登記 |
| 條文內容 | <p><span style="font-family: 新細明體,serif;">為了加強疫苗類藥品的管理，確保疫苗類藥品的品質及安全，爰依據藥事</span> </p><p><span style="font-family: 新細明體,serif;">法第四十二條及七十四條，制定「藥品查驗登記審查準則－疫苗藥品之查</span> </p><p><span style="font-family: 新細明體,serif;">驗登記」。本基準適用於疫苗類藥品查驗登記及檢驗封緘時之品質及安全</span> </p><p><span style="font-family: 新細明體,serif;">的要求。</span> </p><p><span style="font-family: 新細明體,serif;">第一條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">本基準所稱之「疫苗類藥品」，係指由免疫抗原組成的藥品，經</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">由人體投與後可刺激免疫系統，對疾病或感染源產生預防、改善</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">或治療的效果。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">「疫苗」的組成包括經減毒處理的活菌、病毒或寄生蟲；去</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">活化的生物有機體；經處理的活細胞；或天然／純化的免疫</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">原</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括於宿主細胞中製造之基因重組成份、共價結合物、</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">合成抗原、聚核酸</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如質體、去氧核醣核酸疫苗</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">；表現</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">特定異種免疫原之載體細胞、或帶有免疫原之細胞。包括上</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">述多種疫苗的組合。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">「疫苗類藥品」可包括其他體內診斷用之抗原、微生物蛋白</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">質或細菌毒素</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如：肉毒桿菌毒素</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">成分。</span> </p><p><span style="font-family: 新細明體,serif;">第二條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品應檢附之資料：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥的定義及化學、製造與管制的要求</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之製造方法</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之製程管制資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥製程一致性資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">五</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之規格</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">六</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之再製</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">七</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之組成與特性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">八</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之製造業者與設備</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">九</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之製造方法</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一○</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之規格</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">容器與封蓋</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">微生物之管制</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">安定性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一四</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥理及毒性試驗資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一五</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥物動力學資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一六</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">臨床使用文獻</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一七</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物藥品之藥品優良製造規範及確效資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一八</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">檢驗封緘</span> </p><p><span style="font-family: 新細明體,serif;">第三條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥的定義及化學、製造與管制的要求</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">「疫苗類原料藥」定義為尚未配方調製的疫苗類活性成分，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">可為細菌細胞、病毒</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">活病毒、減毒病毒、死病毒</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">或寄生</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">蟲；由細胞中分離</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">或經再純化</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的蛋白質；活體細胞分泌</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">或經再純化</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的抗原以及經由基因重組或合成的醣類、蛋</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">白質或多胜抗原、聚核酸</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如質體或去氧核醣核酸</span><span style="font-family: calibri;"> (</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">ＤＮＡ</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">疫苗</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">或結合以上的物質。「混合疫苗</span><span style="font-family: calibri;"> (combina-</span></p><p><span style="font-family: calibri;"> tion vaccine) </span><span style="font-family: 新細明體,serif;">」則應說明其採收過程及與其他抗原結合及</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">調配的各種活性物質。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥化學、製造與管制的要求：</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">原料藥之製造，無論是發酵、培養、分離、或合成，通常</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">都是從原料藥生產開始，經過中間物質的製備、特性鑑定</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、以及純化而製成原料藥。生物性原料藥的品質及純度不</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">能僅依後續的測試來認定，而需依賴製造及合成過程中的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">管制方能達成。宜執行下列措施以達成正確的管制及最少</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">程度的不純物：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">種源生物及試劑等起始材料的適當品質與純度。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">中間物質加工過程中的管制的制定與運用。</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">一致遵守經確效的加工過程。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">適當的藥物最終</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">放行</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">管制測試。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">原料藥的組成與特性：應提供原料藥的說明及特性說明。對</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">混合疫苗，可參考已核准的許可證申請書。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">原料藥的說明：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列項目：原料藥的生物種名</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">選定的菌株或菌落</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">或化學名稱，包括已建立的名稱。對</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括微生物細胞</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">製成的原料藥的細胞來源、細胞部分</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">或已純化抗原的活性成分及合成原料藥的物理及化學性質</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">亦應加以說明。有關原料藥的化學修飾或接合作用應詳細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">說明，同時應提供存於原料藥內所有非活性物質的表單。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">原料藥的特性：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">應提供原料藥的特性、純度、安定性和製程一致性的測</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試。測試結果應包括諸如格式數據、色譜或光譜的清楚</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">影本、膠體或免疫吸附的照片、細胞計量分析的實際圖</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">表、或其他適當格式的實際數據。數據應經完善整理並</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">充分加註指標以利方便審查。定量分析的結果應用實際</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的數據表示，而不可用一般的「合格」或「不合格」表</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">示。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">原料藥的物理化學特性資料：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一般而言，物理化學特性鑑定應包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">各項：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">紫外線／可見光或質譜儀</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">胺基酸分析</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">胺基酸或核酸序列分析</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">醣類之測定，適當的話，再加上序列分析</span> </p><p><span style="font-family: calibri;"> (5) </span><span style="font-family: 新細明體,serif;">胜圖譜</span> </p><p><span style="font-family: calibri;"> (6) </span><span style="font-family: 新細明體,serif;">雙硫鍵位置的決定</span> </p><p><span style="font-family: calibri;"> (7) </span><span style="font-family: 新細明體,serif;">十二基硫酸鈉─聚丙醯氨凝膠電泳</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">還原態與非還原</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">態</span><span style="font-family: calibri;">) (Sodium Dodecyl Sulfate-Polyacrylamide G-</span></p><p><span style="font-family: calibri;"> el Electrophoresis, SDS-PAGE)</span></p><p><span style="font-family: calibri;"> (8) </span><span style="font-family: 新細明體,serif;">一維或二維</span><span style="font-family: calibri;"> (1D </span><span style="font-family: 新細明體,serif;">或</span><span style="font-family: calibri;"> 2D) </span><span style="font-family: 新細明體,serif;">等電位焦聚電泳分析</span> </p><p><span style="font-family: calibri;"> (9) </span><span style="font-family: 新細明體,serif;">高壓液體層析法</span><span style="font-family: calibri;"> (HPLC) </span><span style="font-family: 新細明體,serif;">、氣相層析法</span><span style="font-family: calibri;"> (GC) </span><span style="font-family: 新細明體,serif;">、液相</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">層析法</span><span style="font-family: calibri;"> (LC) </span><span style="font-family: 新細明體,serif;">、或薄層光譜分析</span><span style="font-family: calibri;"> (thin layer chro-</span></p><p><span style="font-family: calibri;"> matography) </span><span style="font-family: 新細明體,serif;">等各種光譜分析法</span> </p><p><span style="font-family: calibri;"> (10) </span><span style="font-family: 新細明體,serif;">核磁共振光譜分析</span> </p><p><span style="font-family: calibri;"> (11) </span><span style="font-family: 新細明體,serif;">用以偵測包括去氨基、氧化、加工及凝集等型式的相</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">關蛋白質、胺基酸取代、接合及衍生等變形及諸如硫</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">氫基試劑、尿素、殘餘的宿主蛋白質、殘餘的去氧核</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">醣核酸及內毒素等加工過程之污染物所實施的分析方</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">法</span> </p><p><span style="font-family: calibri;"> (12) </span><span style="font-family: 新細明體,serif;">與其他藥品結合的產物，如多抗原胜</span><span style="font-family: calibri;"> (multiple a</span></p><p><span style="font-family: calibri;"> ntigen peptides; MAP) </span><span style="font-family: 新細明體,serif;">或經進一步化學或酵素修飾</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的原料藥，應提供額外的物理化學特性資料。包括產</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">品結合或共軛鍵結的程度，未修飾產物的量，游離物</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的移除</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如毒素、放射性核酸、連接物等</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，及修</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">飾後產物的安定性</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">生物活性：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">應提出原料藥的效價和活性之敘述與結果。應提供有</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">關疫苗的進一步特性資料包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列各項</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">：</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">蛋白質西方墨點分析</span><span style="font-family: calibri;"> (Western blot analysis)</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">或酵素連結免疫吸附分析法</span><span style="font-family: calibri;"> (enzyme-linked imm-</span></p><p><span style="font-family: calibri;"> unosorbent assay</span><span style="font-family: 新細明體,serif;">；</span><span style="font-family: calibri;">ELISA) </span><span style="font-family: 新細明體,serif;">等鑑別測試</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">細胞計量分析</span> </p><p><span style="font-family: calibri;"> C </span><span style="font-family: 新細明體,serif;">適當的神經毒性測試</span> </p><p><span style="font-family: calibri;"> D </span><span style="font-family: 新細明體,serif;">血清分型</span> </p><p><span style="font-family: calibri;"> E </span><span style="font-family: 新細明體,serif;">電泳分型</span><span style="font-family: calibri;"> (Electrophoretic Typing)</span></p><p><span style="font-family: calibri;"> F </span><span style="font-family: 新細明體,serif;">不活化試驗</span> </p><p><span style="font-family: calibri;"> G </span><span style="font-family: 新細明體,serif;">中和分析</span> </p><p><span style="font-family: calibri;"> H </span><span style="font-family: 新細明體,serif;">效價試驗</span><span style="font-family: calibri;"> (Titrations)</span></p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">應提供原料藥之效價及活性證明</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">依製造業者之參考標準組或其他相關標準執行相關的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">體內及體外生物活性測試</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">生物鑑定</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，並提供測試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的結果。應對每種生物鑑定的規格、對照標準品、測</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試方法的確效及可接受誤差範圍作完整的說明，同時</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">也應包括於免疫化學或血清學分析中所使用特定抗體</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的鑑定。</span> </p><p><span style="font-family: 新細明體,serif;">第四條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之製造方法：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應說明原料藥製造及管制的過程，以證明正確的品質管制，及能</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">預防外來因子可能造成的污染。並提供相關的標準操作過程</span><span style="font-family: calibri;"> (S-</span></p><p><span style="font-family: calibri;"> OP) </span><span style="font-family: 新細明體,serif;">資料。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">原料藥</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">應提供用於原料藥製造的材料表單</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">培養基、緩衝液、多</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胜合成用之樹脂，化學物質、色層分析用管柱等</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，材</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料的測試與產品規格、或相關基準等參考文獻。商品化的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">材料，應有供應商的產品規格及分析結果</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">製造標準</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">證</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">明書。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">應說明原料藥純化或製程中使用的單株抗體、酵素及其他</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">蛋白質等試劑、特殊胺基酸及其衍生物、或醣脂等來源，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">包括供應商之證明書、特異性及來源等資料。應提供細胞</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生長之原料藥，例如：血清、胰蛋白等外來因子的測試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">結果。應對各種成分的用途作說明。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">應表列所有使用於製造原料藥與半製品成份之名稱、測</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試方法與規格，或其參考文獻。對於商業化之原料藥，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應有供應商之分析證明與自家檢定結果。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">應表列所有使用於製造原料藥與半製品之特殊試劑與材</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料，如培養基、緩衝液、血清、抗生素、單株抗體、防</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">腐劑。在某些情形，如輔助性之生技產品使用於原料藥</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">之製造過程</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如單株抗體使用於親和性色層分析</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應詳述其製備過程及特性。</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">動物性原料藥、試劑及成分的管制：若於製造過程中有</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">使用由動物來源取得之原料藥時，需證明其不含外來物</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">質，如牛海綿狀腦病變</span><span style="font-family: calibri;"> Bovine Spongiform Encephal-</span></p><p><span style="font-family: calibri;"> opathy (BSE) </span><span style="font-family: 新細明體,serif;">物質，與其他動物病毒。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">申請時應有不含有外來物之確效資料或証明。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">流程圖：應有一份完整製造過程之流程圖，同時應表列其製</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">程管制與試驗項目。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製程：製程中，依其材料來源之不同，應有各相關之資料。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">動物來源</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括禽類之受精卵</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">用於微生物生長或製造重組蛋白質，及用作疫苗的動物性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">來源，應視疫苗特性提供</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列各項資料：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">動物的物種與年齡</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">動物的健康狀況，例如：無特定的病原菌</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">外來物質的篩選與檢疫過程</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">動物飼養之控管，例如：適當的動物隔離過程</span> </p><p><span style="font-family: calibri;"> 5 </span><span style="font-family: 新細明體,serif;">獸醫監督及實驗室監視</span> </p><p><span style="font-family: calibri;"> 6 </span><span style="font-family: 新細明體,serif;">動物預防接種的說明</span> </p><p><span style="font-family: calibri;"> 7 </span><span style="font-family: 新細明體,serif;">對採收的組織及採用方法的說明</span> </p><p><span style="font-family: calibri;"> 8 </span><span style="font-family: 新細明體,serif;">對於牛製品須註明其地區來源及地點</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">病毒來源</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">對用於疫苗製造的病毒種源作詳細的說明，提供的資料應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列各項：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">病毒的起源</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">病毒菌株的譜系資料</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">種批系統</span><span style="font-family: calibri;"> (Seed Lot System) </span><span style="font-family: 新細明體,serif;">的詳細資料</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">維持病毒種源的培養技術</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">細胞來源</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">細胞種批系統</span><span style="font-family: calibri;"> (Cell Seed Lot System) </span><span style="font-family: 新細明體,serif;">：應提供有關微</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物細胞、動物來源</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">昆蟲類、人類及其他哺乳類</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">之細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞或細胞株之細胞受質資料。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">微生物細胞</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">應對微生物的物種、菌株、已知的表現型特性及基因</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">型特性作說明。用於疫苗原料藥的微生物細胞及衍生</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">物包括：整個細胞的疫苗</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">活菌或死菌</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">、天然的溶</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">菌產物或已純化的免疫原、重組的去氧核醣核酸製品</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、接合物質及質體去氧核醣核酸疫苗。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">應提供製造用各種菌株的歷史及特性鑑定，並對菌株</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">作完整的說明，包括：</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">單離的起源</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">物種</span> </p><p><span style="font-family: calibri;"> C </span><span style="font-family: 新細明體,serif;">生物化學特性</span><span style="font-family: calibri;">(</span><span style="font-family: 新細明體,serif;">發酵等</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> D </span><span style="font-family: 新細明體,serif;">菌株鑑別特性鑑定</span><span style="font-family: calibri;">(</span><span style="font-family: 新細明體,serif;">血清類型等</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> E </span><span style="font-family: 新細明體,serif;">病毒的感染能力</span><span style="font-family: calibri;">(</span><span style="font-family: 新細明體,serif;">包括已經執行的減毒方法</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> F </span><span style="font-family: 新細明體,serif;">已知的基因特性鑑定</span><span style="font-family: calibri;">(</span><span style="font-family: 新細明體,serif;">標記、插入、剪除等</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> G </span><span style="font-family: 新細明體,serif;">質體</span> </p><p><span style="font-family: calibri;"> H </span><span style="font-family: 新細明體,serif;">菌株突變的機率</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">遺傳安定性</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">動物細胞</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">應說明對於存於動物起源細胞受質內的外來污染因子</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">所採取的預防、排除或不活化措施。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">初代細胞：應提供製造初代細胞的起源組織及用途說</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">明。提供初代細胞株資料，包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列各</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">項：</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">動物的物種及年齡，及初代細胞的組織來源</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">該初代細胞出處的動物健康狀況，例如：無特定的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">病原菌</span> </p><p><span style="font-family: calibri;"> C </span><span style="font-family: 新細明體,serif;">用以確保動物適當性的動物飼養方式</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">隔離過程等</span> </p><p><span style="font-family: calibri;"> )</span></p><p><span style="font-family: calibri;"> D </span><span style="font-family: 新細明體,serif;">用以確保動物適當性的獸醫及實驗室監視</span> </p><p><span style="font-family: calibri;"> E </span><span style="font-family: 新細明體,serif;">初代細胞受質製備的說明</span> </p><p><span style="font-family: calibri;"> F </span><span style="font-family: 新細明體,serif;">用以證明無外來因子存在的測試及結果</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">細胞株</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製造的受質應包含人類或動物來源的連續細胞株或兩</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">倍體</span><span style="font-family: calibri;"> (Diploid) </span><span style="font-family: 新細明體,serif;">細胞株。</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">人類細胞受質，應包括使用的材料與方法、起始的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">組織或器官、種族與地理的起源、年齡、性別及一</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">般生理狀況的說明，如已知捐贈者之疾病史，應提</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">供測試結果。</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">動物細胞受質，應包括物種、體系、起始的組織或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">器官、地理起源、年齡、性別及一般生理狀況，並</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">可能存於細胞內的外來因子。</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">基因構築體與重組細胞株</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">對從重組</span><span style="font-family: calibri;"> DNA </span><span style="font-family: 新細明體,serif;">製品及使用重組</span><span style="font-family: calibri;"> DNA </span><span style="font-family: 新細明體,serif;">的細胞受質，應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">提供宿主細胞，及重組</span><span style="font-family: calibri;"> DNA </span><span style="font-family: 新細明體,serif;">來源及功能的資料，包括</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">宿主細胞：應說明宿主細胞的來源、相關的表現型及</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">基因型、細胞安定性及特性鑑定的結果。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">基因構築體</span><span style="font-family: calibri;"> (Gene Construct) </span><span style="font-family: 新細明體,serif;">：應說明引入宿主細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞之基因製備方法，及限制切割圖。並提供完整核</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">酸序列、表現架構之調節因子、轉譯的胺基酸序列</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，及重要序列特色。</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">載體：應提供載體的資料，包括載體來源及功能的說</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">明，例如：複製的起源、抗生素耐受性基因、啟動基</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">因及增強基因等。應提供構建載體之限制切割圖部</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">位及特性鑑定之重要基因標記。</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">最終基因架構：應說明製造最終重組基因架構的過程</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，包括基因片段、載體、或其他基因的組合過程加以</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">說明，並提供最終基因架構之限制切割圖。</span> </p><p><span style="font-family: calibri;"> (5) </span><span style="font-family: 新細明體,serif;">重組細胞株：應提供將最終基因架構移轉至宿主的方</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">法、移轉的機制、複製的數量及轉移後宿主細胞內</span><span style="font-family: calibri;"> (</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">加入體外遺傳因子</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的生理狀況等資料。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">細胞庫系統：應說明細胞庫建立的過程，包括：製備細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞庫的方法、低溫保存方式及細胞庫之管制等資料。應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">避免微生物污染及防止與其他細胞交互污染。並預防細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞庫儲存環境產生劇烈變化及適當警戒措施，例如：將</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">細胞庫存於不同處的多個冷藏庫內。</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">種細胞庫</span><span style="font-family: calibri;"> (MCB)</span><span style="font-family: 新細明體,serif;">：應提供種細胞庫內細胞歷史及特性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">鑑定。</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">對基因重組製品的種細胞庫細胞受質是指從原始單</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一細胞複製，含有合適基因構築體之感染細胞。</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">對非基因重組製品，細胞受質是指來自選定用於製</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">備種細胞庫的母系細胞株。應提供選作種細胞庫的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">兩倍體細胞株資料。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">工作細胞庫</span><span style="font-family: calibri;"> (WCB)</span><span style="font-family: 新細明體,serif;">：應詳述由種細胞庫衍生至工作細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞庫之過程，包括工作細胞庫之鑑別系統、儲存步驟</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及其細目。對於每一新工作細胞庫，須進行與現有細</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">胞庫各項定性及特性分析之比較。必要時應說明此工</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">作細胞庫之繼代數，以確保其保護性抗原致毒性因子</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">之存在。並應詳述確保培養純度與鑑別之方法與步驟</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">最終產品細胞</span><span style="font-family: calibri;"> (End of production cells; EPC) </span><span style="font-family: 新細明體,serif;">：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應說明所使用最終生產細胞之特性，以證明該生產系</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">統之一致性。應包括最終生產細胞表現型與基因型標</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">記之分析結果，以確認其鑑別與純度，並證明其不受</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">外來物質污染。同時應提供該基因構築體之限制酵素</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">分析結果。</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">細胞庫之特性與試驗：應說明有關庫存細胞之特性與</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試驗，包括細胞受質之鑑別、純度與適合性試驗之資</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料及其結果，以確保其可用於製造。若細胞來源為複</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">細胞動物</span><span style="font-family: calibri;"> (metazoan cells) </span><span style="font-family: 新細明體,serif;">，應提供對於種細胞庫</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">與工作細胞庫之負荷菌</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">細菌及真菌</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">與黴漿菌測試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">結果，以及可能污染該細胞株之病毒檢測結果。</span> </p><p><span style="font-family: calibri;"> 5 </span><span style="font-family: 新細明體,serif;">細胞培養與採收</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">細胞的培養：應對培養過程、生長曲線或生長特性作</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">說明。並提供純度、效價、抗原生產等的管制及測試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">時間點資料。也應說明對污染管制所採取的措施。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">細胞的採收：應說明原料藥由細胞分離所使用的採收</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">方法</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">沉澱、離心、過濾</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，並提供採收的標準及產</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">量等資料。對維持採收過程無菌狀態及預防污染所採</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">取的措施加以說明，對生物負荷量試驗監視。如果原</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料藥在後續處理前需保存，則應說明儲存情況及時間</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">限制。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">純化與後續處理</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應說明純化過程，並檢附鑑定、純度、濃度及與產品或非</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">產品有關的不純物的分析測試方法。於培養時使用的抗生</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">素及其他成分</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如生長因子、抗體</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，應於使用前加以</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">排除並確保預防交互污染的過程。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">執行適當的不活化步驟：應說明</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">不活化前的純度。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">去活化的方法及試劑。</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">預防凝集及確保不活化劑均質化的方法。</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">製造過程中實施不活化或滅菌的階段。</span> </p><p><span style="font-family: calibri;"> (5) </span><span style="font-family: 新細明體,serif;">監視的參數：對去活化或滅菌方法的適當性說明。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">純化步驟：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">應說明抗原成分純化的目的及原理</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">使用的方法，包括如色層分析用管柱、超速離心機</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、超速過濾器及單株抗體等試劑或設備。</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">產量。</span> </p><p><span style="font-family: calibri;"> C </span><span style="font-family: 新細明體,serif;">純化過程的測試</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如：</span><span style="font-family: calibri;">ELISA </span><span style="font-family: 新細明體,serif;">之敏感度及特異性</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> D </span><span style="font-family: 新細明體,serif;">純化過程中無菌狀態或生物負荷量試驗的監視，及</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">預防污染所採取的警戒措施。</span> </p><p><span style="font-family: calibri;"> E </span><span style="font-family: 新細明體,serif;">純化用色層分析管柱及吸附劑之再使用及</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">或</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">再</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生。</span> </p><p><span style="font-family: calibri;"> F </span><span style="font-family: 新細明體,serif;">殘餘的不純物及試劑的監視。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">流程圖及批次記錄應提供純度、鑑定及生物活性的管</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">制及測試時間點的資料。對純化原料藥之最終認定標</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">準。如果經純化的原料藥在進一步處理前需保存時，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應對其儲存情況及時間限制加以說明。</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">安定性試驗：應對純化後中間物質在每個過程</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">吸收、添加穩定劑、添加防腐劑、低壓冷凍乾燥儲存、</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">乾燥</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的安定性的加以說明，並執行監視生物負荷量試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">驗及所採取預防污染的警戒措施。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">去毒性：對類毒素或含有類毒素的疫苗，應說明毒素成</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">分的去毒性過程</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">去毒性所使用的方法及試劑。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">實施去毒性的製造過程。</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">對去毒性使用方法的適當性加以證明。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">五</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">合成之原料藥：合成原料藥包括線性或複合之合成胜類</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及經修飾合成或半合成之免疫原</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如</span><span style="font-family: calibri;"> lipopeptides </span><span style="font-family: 新細明體,serif;">、攜</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">帶蛋白質之胜或攜帶蛋白質結合物之多醣體</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">合成胜類：應提供多胜合成及純化過程等的資料。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">經修飾合成或半合成之免疫原</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">對原料藥或中間物質經化學或酵素修飾製成，如：將</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">免疫原接合至載體、將毒素以酵素或化學方法減毒及</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">純化。此種修飾作用可能會改變原料藥的免疫抗原性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、毒性、安定性、或原料藥之藥動學特性。</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">製造方法：應說明</span> </p><p><span style="font-family: calibri;"> A </span><span style="font-family: 新細明體,serif;">為確保結合或修飾方法的適當性，應說明原料藥的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">說明及標準。</span> </p><p><span style="font-family: calibri;"> B </span><span style="font-family: 新細明體,serif;">應說明製造過程及方法、製程管制、產品鑑定及生</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">物活性的測試、以及純化的過程。</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">產品規格：應檢附每一經修飾原料藥之規格，包含鑑</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">別、純度、效價、物理化學測定及安定性試驗。若該</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">衍生物之檢驗結果將紀錄於藥品最終放行成績書，則</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">每一規格均應提供包含變異性估計值與上下限之確效</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">報告。未反應初始原料藥與製程中試劑之移除步驟須</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">經確效，否則應有其殘餘量規格。</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">批次記錄：應提供完整</span><span style="font-family: calibri;">(</span><span style="font-family: 新細明體,serif;">加註簽名蓋章</span><span style="font-family: calibri;">)</span><span style="font-family: 新細明體,serif;">的代表性批次</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">記錄。</span> </p><p><span style="font-family: 新細明體,serif;">第五條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之製程管制資料：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製程管制</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應對流程圖中的製程中採樣及測試方法作說明，應建立接受</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">或拒絕該製程中批次的標準。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製程確效</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供可能影響原料藥規格的重要製程或因子所作的確效研</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">究報告。確效研究報告及統計數據應能證明與產品規格及品</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">質相關製程的差異性。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">生長：應依據相關紀錄，提供每個生長過程的生長曲線或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生長特性的鑑定。包括能證明抗原製造效率的數據，及在</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生長情況下能顯示基因標記的安定性數據。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">採收：應依紀錄提供採收的產量、純度及效價。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">不活化：應依紀錄提供不活化或滅菌曲線的描述，也應測</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">量殘餘活性的方法，及靈敏度。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">純化：應提供產量、純度及生物活性的資料。並對不純物</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">試劑、內毒素、細胞蛋白質或核酸及其他殘餘的汙染物</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">管制。應該採用公認的標準</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如：國際單位</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">來進行比</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">較。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">五</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">微生物學：應對製程中，用於培養基滅菌、防腐劑的效率</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、去污染、細胞廢棄前的去活化確效加以說明。如果該原</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料藥為無菌藥品時，應符合「無菌製程確效」之相關資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物負荷量之管制：對非為無菌狀況下的製程，應對生物負</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">荷量試驗進行測試。</span> </p><p><span style="font-family: 新細明體,serif;">第六條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥製程一致性資料：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">每種疫苗成分製程至少要用</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">最好是連續的</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">三批原料藥以驗證</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">其製程之一致性。應說明對照標準品之建立與使用。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">對照標準品：應敘述一級對照標準品與工作對照標準品之製</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">備、特性與安定性。應詳述核定新對照標準品之過程與接受</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">標準。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">放行試驗：應檢附各批次之放行檢驗結果及其他相關資料</span><span style="font-family: calibri;"> (</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">如檢驗成績書</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: 新細明體,serif;">第七條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之規格：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">規格</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">各原料藥之規格與檢驗應包括鑑別、純度、效價</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">生物活性</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">、與效價有關之物理化學測定，必要時應含安定性試驗。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">對於高純度物質，純度應參照理論組成</span><span style="font-family: calibri;"> (theoretical com-</span></p><p><span style="font-family: calibri;"> position) </span><span style="font-family: 新細明體,serif;">表示。於某些情況下，最終放行報告中應包含抗</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">原成分</span><span style="font-family: calibri;"> (component antigens) </span><span style="font-family: 新細明體,serif;">其安定中間產物之檢驗結果</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，並應提供每項規格之確效評估</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包含變異性及信賴區間</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">不純物之資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應包含原料藥中不純物之鑑別與含量分析數據</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如凝膠電泳</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">法、管柱沖提、西方墨點法等</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">。應加以鑑定與定量之不純</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">物包括：</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">與產品相關之不純物</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">如抗原於製程或儲存時產生之變異</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">或改變</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">與製程相關之不純物：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">培養基成分</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">細胞受質蛋白質或核酸</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">純化過程中未去除之試劑</span> </p><p><span style="font-family: 新細明體,serif;">第八條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類原料藥之再製</span><span style="font-family: calibri;"> (Reprocessing) </span><span style="font-family: 新細明體,serif;">：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">對於各原料藥可能再製之程序應載明：</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">於製程管制或規格中訂定出須再製之條件或標準</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">再製步驟</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">再製步驟之標準操作程序</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">應增加或經修定之製程管制或規格</span> </p><p><span style="font-family: calibri;"> 5 </span><span style="font-family: 新細明體,serif;">批次生產紀錄中應註明再製產品之批號與相關文件</span> </p><p><span style="font-family: calibri;"> 6 </span><span style="font-family: 新細明體,serif;">確保再製批次產品之鑑別、純度、效價與安定性之確效評估</span> </p><p><span style="font-family: 新細明體,serif;">第九條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之組成與特性：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">「疫苗類藥品」係指經配方、調製、充填、包裝供即時使用</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藏最終劑型，可能含有其他活性或非活性成分包括佐劑、保</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">腐劑、安定劑及</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">或</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">賦形劑。疫苗之配方包括稀釋、吸附</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">、與佐劑或添加物混合及</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">或</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">減壓冷凍乾燥來製成藥品。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應包含最終製品中所有原料藥及賦形劑的資料。如成分中有</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">使用專利的製備或混合物時，應提供完整資料。對人類或動</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">物起源的成分，應提供能證明其無外來因子的測試結果或分</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">析證明書。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">組成、規格、一致性及確效</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">組成</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供藥品所有成分，包括原料藥及其他內含物，以及其</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">單位劑量。對某些非活性物質，其數量可用濃度百分比或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">體積莫耳濃度表示。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">原料藥：應提供每種原料藥的表單。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">賦形劑：應提供最終製品內非活性成分的表單、分析證</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">明書或測試方法、測試結果等。賦形劑包括</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">下列各項：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">稀釋液</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括其體積莫耳濃度、酸鹼值等</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">填充劑</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">吸附劑</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">非佐劑</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">安定劑</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如醣類、防潮劑</span><span style="font-family: calibri;">)</span></p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">佐劑：應包含化學處方，及各種佐劑每單位劑量的數量</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">防腐劑：應提供其化學名稱及商品名，於單劑原料藥中</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">添加防腐劑的目的及效能。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">規格及測試方法：應對產品之鑑定、純度、效價及每批製</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">品之一致性之測試方法加以說明。並提供原料藥的規格，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及至少連續三批製品的檢驗成績書：及分析結果。</span> </p><p><span style="font-family: calibri;"> 1 </span><span style="font-family: 新細明體,serif;">性狀：應描述其物理狀態</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">冷凍乾燥固體、粉末、液體</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">、顏色、及澄清度。</span> </p><p><span style="font-family: calibri;"> 2 </span><span style="font-family: 新細明體,serif;">鑑別：應描述鑑別試驗之方法及其特異性與靈敏度之評</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">估。</span> </p><p><span style="font-family: calibri;"> 3 </span><span style="font-family: 新細明體,serif;">純度及不純物：應包括成品純度之分析及不純物之鑑別</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">與定量。若該不純物係於製程中加入或形成，應訂定其</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">可接受之範圍與規格。</span> </p><p><span style="font-family: calibri;"> 4 </span><span style="font-family: 新細明體,serif;">效價：應具備該藥品效價分析之資料，包括分析方法之</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">靈敏度、特異性、變異性、及可接受之範圍。</span> </p><p><span style="font-family: calibri;"> 5 </span><span style="font-family: 新細明體,serif;">檢驗成績書：</span> </p><p><span style="font-family: calibri;"> (1) </span><span style="font-family: 新細明體,serif;">應註明批號、檢驗日期、檢驗人員及負責人簽名</span> </p><p><span style="font-family: calibri;"> (2) </span><span style="font-family: 新細明體,serif;">應包括所有原料藥及成品之檢驗成績書</span> </p><p><span style="font-family: calibri;"> (3) </span><span style="font-family: 新細明體,serif;">應依規格逐項檢驗</span> </p><p><span style="font-family: calibri;"> (4) </span><span style="font-family: 新細明體,serif;">原料藥檢驗成績書應為所附成品批次使用之原料藥檢</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">驗成績書</span> </p><p><span style="font-family: calibri;"> (5) </span><span style="font-family: 新細明體,serif;">檢驗結果為數值者應以數據表示，檢驗方法為比對標</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">準品者可以「</span><span style="font-family: calibri;">Pass</span><span style="font-family: 新細明體,serif;">」表示</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">一致性：應提供抽樣計畫，並詳述用以確保成品之鑑別、</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">純度、強度及／或效價之試驗方法，以及各批次間一致性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">之資料與成品規格，且應包括至少連續三批成品之檢驗成</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">績書及檢驗結果。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">確效：應提供放行試驗之每項方法的特異性、靈敏度與變</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">異性之確效評估。包括對照標準品及其確效。若使用公定</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">書之分析方法，應說明其來源依據。</span> </p><p><span style="font-family: 新細明體,serif;">第一○條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之製造業與流程：</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供包括委託代理商在內的所有從事藥品製造及測試之</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製造業者的名稱及住址，並對其責任加以說明。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供藥品的製造流程，包括滅菌操作、無菌處理過程、</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">低壓冷凍乾燥及包裝等過程作詳細的說明。需提供流程圖</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">來顯示製造過程、使用的設備與材料、實施操作的房間或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">區域，及每一個製造過程中所實施的製程中管制及測試的</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">表單。應題供藥品的總製造記錄</span><span style="font-family: calibri;"> (Master Production R-</span></p><p><span style="font-family: calibri;"> ecord, MPR) </span><span style="font-family: 新細明體,serif;">，包括完整的吸收</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">適當的話</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">、調配、裝</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">填、標示及包裝的製造說明。</span> </p><p><span style="font-family: 新細明體,serif;">第一一條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">容器與封蓋：應有製程中所用之容器與封蓋對於原料藥及產品</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">之合適性評估測試，如吸附、可滲出物、生物測試等。並應有</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">儲存期限中容器及封蓋完整性之證明及供應商資訊。若容器或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">封蓋系統已獲許可，應具備許可證明供參。</span> </p><p><span style="font-family: 新細明體,serif;">第一二條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">微生物之管制</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供「無菌製程確效」中所述之相關資料。</span> </p><p><span style="font-family: 新細明體,serif;">第一三條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">安定性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應敘述產品之安定性以訂定其儲藏條件與有效期限，必要時應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">有半製品或調配原液在特定儲存或運送條件下之安定性及其確</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">效資料。安定性試驗報告應依行政院衛生署公告之「藥品安定</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">性試驗準則」內容確實執行，並檢附實驗方法、統計分析及定</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">量分析方法的確效等資料。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">安定性試驗計劃書：應提供</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">但不限於</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">下列各項安定性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">測試：</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">效價</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">物理化學規格</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">低壓冷凍乾燥時的水分含量</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">酸鹼值</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">五</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">無菌或負荷菌管制</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">六</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">經冷凍或解凍後之細胞存活率</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">安定性資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">應提供藥品於最終容器或封閉系統、儲存狀況下，有效期</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">限的結果。對低壓冷凍乾燥儲存的製品，應提供架存期限</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">的數據。冷藏製品，應提供製品經過冷藏─解凍循還次數</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">後的安定性數據。</span> </p><p><span style="font-family: 新細明體,serif;">第一四條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥理及毒性試驗資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品的菌種</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括亞種</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的變更、製程改變、配方改變</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及結構等些微差異，可能對產品的免疫產生能力及毒理等作用</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">產生重大影響，因此需藉適當的動物模式，觀察產品在活體中</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">產生任何非預期的免疫及毒理作用，並在毒性試驗或臨床試驗</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">時觀察此作用。藥品之藥理及毒性試驗應符合行政院衛生署「</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥品非臨床試驗安全性規範」</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 2) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: 新細明體,serif;">第一五條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥物動力學資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品之申請應說明其吸收、分布、代謝、排泄及療效等</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">作用。視藥品特性來提供藥動學、藥效學等人體及動物資料以</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">供審核，可參考衛生署出版之「藥品生體可用率及生體相等性</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試驗基準及相關資料」</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 3) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: 新細明體,serif;">第一六條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">臨床使用文獻</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品查驗登記時，除應檢附國外臨床使用文獻等資</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料外，另應再依據衛生署「藥品優良臨床試驗規範」</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">考文獻</span><span style="font-family: calibri;"> 4) </span><span style="font-family: 新細明體,serif;">及相關規定申請國內供查驗登記用藥品臨床試</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">驗</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">得檢附國內臨床試驗報告資料，或同時檢送國內臨床</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試驗計畫書，以供審查</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">。惟如欲免除國內臨床試驗，則</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">可依本署歷次免除國內臨床試驗品項之公告，正式向本署</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">申請免除國內臨床試驗。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">疫苗類藥品免除國內臨床試驗之原則</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 5) </span><span style="font-family: 新細明體,serif;">：原</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">產國已上市、且具有十大先進國採用證明者，其有效性及</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">安全性有發表文獻可資證明，且符合左列各項之一者：</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">因可受試人數太少，或為預防緊急、嚴重之感染性疾患</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及／或其併發症，或因特殊需要等，經衛生署審查認定</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，係為無其他藥品可取代之疫苗。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">所申請疫苗之保護效果或抗體反應，有適當之亞裔人種</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">資料以顯示無人種差異</span><span style="font-family: calibri;"> (Ethnic Insensitive) </span><span style="font-family: 新細明體,serif;">，且其</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">所預防之特定微生物</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">群</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，亦無區域性微生物菌種</span><span style="font-family: calibri;"> (</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">包括亞型</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">的差異，或有具體資料顯示其免疫作用對不</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">同微生物抗原，具有交互保護的效果，並有足夠評估國</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">人安全性</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">例如對盛行率高之國人肝炎患者的疫苗反應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">等</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">資料。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">疫苗類藥品可免除國內臨床試驗之適用申請條件，以預</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">防接種用主動免疫類疫苗為主。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">疫苗類藥品應提供上述之資料向衛生署申請免除國內臨</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">床試驗。衛生署得要求原申請廠商提供具體文獻、資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，包括國內使用之效益評估</span><span style="font-family: calibri;"> (Cost-Benefit Analysis)</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">等資料，以便進行必要之審核工作。</span> </p><p><span style="font-family: 新細明體,serif;">第一七條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物藥品之藥品優良製造規範及確效資料</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物藥品之製造及輸入，應符合藥事法及相關規定。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">從事人用生物藥品製造業者，應聘具有生物藥品製造專</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">門知識，並有五年以上製造經驗之技術人員，駐廠負責</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">製造。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">製造、輸入之藥品應符合「藥品優良製造規範」。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">生物藥品原液</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">原料藥</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">之輸入，以生物藥品製造業者</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">為限。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">生物製劑或生物技術產品工廠應有獨立</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">棟</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">之廠房，</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">其空氣處理系統亦應各自獨立。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">五</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">生物製劑或生物技術產品原料藥，應視實際需要，具備</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">必需之製造、加工或分裝、包裝設備。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">六</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">生物製劑或生物技術產品等應視檢驗需要，設置生菌數</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">試驗、滅菌檢查、熱原試驗、安全試驗、生物檢定等之</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">場所、設施及設備。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">七</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">為配合我國</span><span style="font-family: calibri;"> GMP </span><span style="font-family: 新細明體,serif;">之實施，確保輸入藥品品質，藥廠確</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">實符合</span><span style="font-family: calibri;"> GMP </span><span style="font-family: 新細明體,serif;">規定，國外藥廠於藥品登記前，應先檢附</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">該廠工廠資料</span><span style="font-family: calibri;"> (Plant Master File</span><span style="font-family: 新細明體,serif;">；</span><span style="font-family: calibri;">PMF) </span><span style="font-family: 新細明體,serif;">申請備查。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">生物藥品之輸入，應依相關之基準取得生物藥品之工廠</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">資料</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括原料藥及製劑</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥廠應依「藥品優良製造確效作業基準」</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 6)</span></p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，以適當之方法，針對下列事項之適當性，進行確效：支</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">援系統</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">包括供水與空氣處理系統</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">，設備之安裝、操作</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及其性能，設備之清潔，製程及各種分析方法等。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">屬於生物藥品特有之確效作業，藥廠應自行檢附資料送審</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。行政院衛生署亦將適時公告相關之要求。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">四</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥物工廠、生物製劑製藥廠應於民國九十一年七月前設置</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">動物實驗管理小組。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">依據動物保護法規定</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 7) </span><span style="font-family: 新細明體,serif;">，農委會頒佈動物</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">實驗管理小組設置辦法。</span> </p><p><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">國內生物科技、製藥等所有利用實驗動物的機構，都必</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">須成立動物實驗管理小組。成員至少包括一位獸醫師或</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">經由農委會委託培訓單位訓練合格的實驗動物專業人員</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，負責審查該機構進行實驗動物的研究計畫，監督、並</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">提供有關實驗動物飼養設施改善建議。同時，每年定期</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">向實驗動物倫理委員會提出監督報告。</span> </p><p><span style="font-family: 新細明體,serif;">第一八條</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">檢驗封緘</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">輸入或製造之疫苗類藥品，應申請檢驗封緘後，始得銷售</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">二</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">凡製造、輸入疫苗之廠商，應檢附生物藥品檢驗封緘申請</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">書、包裝清單、原產國國家檢定機構之檢驗合格證明，但</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">原廠若經國家檢定機構認可授權自行檢驗者，可用原廠之</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">檢驗紀錄及成績書代替</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">上述兩項資料，國產製品得免附</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">，行政院衛生署核發之藥品許可證及核准容器標籤仿單</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">影印本、生物藥品製程、檢驗方法、規格及有關文獻、本</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">批生物藥品製程及成品之檢定紀錄</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">含製程分裝數量紀錄</span> </p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">、成績書，向衛生署藥物食品檢驗局申請；國產製品應</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">由該廠自行檢定合格完成包裝後始得為之。經該局審查與</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">規格相符時，即派員查核其輸入運送、貯存之溫度紀錄符</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">合後；抽取樣品檢驗，並將所請封緘之生物藥品悉數先行</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">封存原處．由廠商自行保管，俟檢驗合格後，即派員拆封</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，按其核准之包裝，個別加貼藥物檢查證以完成封緘手續</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，並核發「生物藥品封緘證明書」。前述之檢驗，得由本</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">署藥物食品檢驗局依實際需要決定檢驗項目</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">參考文獻</span><span style="font-family: calibri;"> 8</span></p><p><span style="font-family: calibri;"> ) </span><span style="font-family: 新細明體,serif;">。</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">三</span><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">基於配合防疫及作業需要下列生物藥品，得由衛生署藥物</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">食品檢驗局以書面審查有關規定資料，並派員查核其輸入</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">運送、貯存之溫度紀錄符合後按其核准之包裝，個別加貼</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">藥物檢查證以完成封緘手續，並核發「生物藥品封緘證明</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">書」。必要時，藥物食品檢驗局仍得抽樣，俟檢驗合格後</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">，再加予封緘。</span> </p><p><span style="font-family: 新細明體,serif;">參考文獻：</span> </p><p><span style="font-family: calibri;">1 Guidance for Industry: Content and Format of Chemistry, Manuf-</span></p><p><span style="font-family: calibri;"> acturing and Controls Information and Establishment Descripti-</span></p><p><span style="font-family: calibri;"> on Information for a Vaccine or Related Product - FDA/CBER/1/5</span></p><p><span style="font-family: calibri;"> /1999</span></p><p><span style="font-family: calibri;">2 87.6.24.</span><span style="font-family: 新細明體,serif;">衛署藥字第</span><span style="font-family: calibri;"> 87040788 </span><span style="font-family: 新細明體,serif;">號公告之「藥品非臨床試驗安全性規範</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">」</span> </p><p><span style="font-family: calibri;">3 87.5. </span><span style="font-family: 新細明體,serif;">衛生署出版之「藥品生體可用率及生體相等性試驗基準及相關資</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">料」</span> </p><p><span style="font-family: calibri;">4 85.11.20 </span><span style="font-family: 新細明體,serif;">衛署藥字第</span><span style="font-family: calibri;"> 85067127 </span><span style="font-family: 新細明體,serif;">號公告之「藥品優良臨床試驗規範」</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">及</span><span style="font-family: calibri;"> 89.12.12.</span><span style="font-family: 新細明體,serif;">衛署藥字第</span><span style="font-family: calibri;"> 0890035812 </span><span style="font-family: 新細明體,serif;">號之相關規定</span> </p><p><span style="font-family: calibri;">5 87.12.30. </span><span style="font-family: 新細明體,serif;">以衛署藥字第</span><span style="font-family: calibri;"> 87074774 </span><span style="font-family: 新細明體,serif;">號，公告第三次公告得免除國內臨</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">床試驗之新藥品，包括疫苗類藥品及治療精神或免疫系統慢性疾病藥品</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">等二類藥品之相關規定</span> </p><p><span style="font-family: calibri;">6 88.04.13. </span><span style="font-family: 新細明體,serif;">衛署藥字第</span><span style="font-family: calibri;"> 88018122 </span><span style="font-family: 新細明體,serif;">號公告「藥品優良製造確效作業基準</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">」</span> </p><p><span style="font-family: calibri;">7 87.11.4. </span><span style="font-family: 新細明體,serif;">總統華總</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">一</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">義字第</span><span style="font-family: calibri;"> 8700224370 </span><span style="font-family: 新細明體,serif;">號令公布之「動物保護</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">法」及</span><span style="font-family: calibri;"> 89.1.19. </span><span style="font-family: 新細明體,serif;">以</span><span style="font-family: calibri;"> (</span><span style="font-family: 新細明體,serif;">八九</span><span style="font-family: calibri;">) </span><span style="font-family: 新細明體,serif;">農牧字第</span><span style="font-family: calibri;"> 890100554 </span><span style="font-family: 新細明體,serif;">號公告之「動物保</span> </p><p><span style="font-family: calibri;"> </span><span style="font-family: 新細明體,serif;">護法施行細則」</span> </p><p><span style="font-family: calibri;">8 87.06.20. </span><span style="font-family: 新細明體,serif;">為簡化生物藥品檢驗封緘申請手續，以衛署藥字第</span><span style="font-family: calibri;"> 8701949</span></p><p><span style="font-family: calibri;"> 5 </span><span style="font-family: 新細明體,serif;">號公告「生物藥品檢驗封緘作業規定」</span> </p><p><span style="font-family: calibri;"> </span></p> |
| 發佈日期 | 2013-12-05 |
| 附件檔案 |