10.13.1 Reasons for Dedication

专用的原因

Reasonsfor dedication of equipment may be quality driven (such as to avoidcross-contamination of one active ingredient into another product) or may bebased on business considerations (such as for production efficiency).Regulatory agencies recommend dedicated equipment and/or facilities in certain situations.For example, the PIC/S recommendations state that “Dedicatedequipment should be used for products which are difficult to remove (e.g.,tarry or gummy residues in bulk API manufacturing), for equipment which isdifficult to clean (e.g., bags for fluid bed dryers), or for products with ahigh safety risk (e.g., biological or products of high potency which may bedifficult to detect below an acceptable limit)” (22). That PIC/Sdocument also states that “For certain allergenicingredients, penicillins, cephalosporins or potent steroids and cytotoxics, thelimit should be below the limit of detection by best available analyticalmethods. In practice this may mean that dedicated plants are used for theseproducts.” Additionally, the ANVISAResolution – RDC No. 17 states that “There should be usedsegregated facilities and dedicated to the production of certain medicationssuch as certain biological preparations (e.g., live microorganisms) and thehighly sensitizing materials (e.g., penicillin, cephalosporin, carbapenem andother beta-lactic derivatives) in order to minimize the risk of serious damageto health due to cross contamination”, and further that “Theproduction of certain highly active products, such as some antibiotics, certainhormones, cytotoxic substances should be held in segregated areas”(40). Finally, there are the U.S. FDA draft recommendations about dedicationfor beta-lactams (41).      

设备专用的原因可能是质量原因(例如避免产品之间的交叉污染)或基于商业考虑 (如为了提高生产效率)。对于某些情况，监管机构建议使用专用设备和/或厂房。例如，PIC / S建议“难以去除的产品 (如API生产中柏油或粘性残留)、难以清洁的设备(如流化床干燥器过滤袋)，或安全风险高的产品 (如，生物制剂或在可接受限下难以检测到的高活性产品)，应采用专用设备”(22)。PIC / S指南也指出：“对于某些致敏性成分，如青霉素、头孢菌素或高活性的类固醇和细胞毒素，限度应低于现有最好的分析方法的检测限。在实际操作中这可能意味着使用专用工厂生产这些产品。”另外，ANVISA决议-RDC 第17号指出“应使用专用厂房用于某些药品如生物制剂(如活的微生物)和高致敏性产品(如青霉素、头孢菌素、碳青霉素和其他β-内酰胺衍生物)，以减少由于交叉污染带来的严重损害健康的风险”，并进一步要求“生产一些高活性产品，比如部分抗生素、激素、细胞毒性物质应在隔离的区域进行”(40)。最后，还有美国FDA关于β-内酰胺生产线专用的建议草案(41)。      

 Riskassessments and appropriate controls should be considered in cases whereregulatory documents may be unclear or overly strict on the requirement fordedication or segregation for manufacturing.     

当规范性文件对于专用或隔离生产的要求可能不清楚或过于严格时，应进行风险评估并进行适当控制