BP 非无菌制剂的微生物限度.doc

Appendix XVI D. Microbiological Quality of Non- sterile Pharmaceutical Preparations and Substances 非无菌制剂的微生物限度(Ph. Eur. general text 5.1.4) The presence of certain micro-organisms in non-sterile preparations may have the potential to reduce or even inactivate the therapeutic activity of the product and has a potential to adversely affect the health of the patient. Manufacturers therefore have to ensure a low bioburden of finished dosage forms by implementing current guidelines on Good Manufacturing Practice during the manufacture, storage and distribution of pharmaceutical preparations. 非无菌制剂中存在一定量的微生物可能导致药物的治疗活性降低或消失，并对患者健康有着潜在的危害。因此生产商应在药品生产、储存、运输过程中实施GMP管理，使制剂的微生物负荷保持在低水平。 Microbial examination of non-sterile products is performed according to the methods given in general chapters 2.6.12 and 2.6.13. Acceptance criteria for non-sterile pharmaceutical products based upon the total aerobic microbial count (TAMC) and the total combined yeasts/moulds count (TYMC) are given in Tables 5.1.4.-1 and 5.1.4.-2. Acceptance criteria are based on individual results or on the average of replicate counts when replicate counts are performed (e.g. direct plating methods). 非无菌制剂的微生物检测按照通则2.6.12和2.6.13的方法执行。非无菌制剂的微生物限度基于表5.1.4-1和5.1.4-2的需氧微生物总数（TAMC）及酵母菌/霉菌总数（TYMC）。接受标准适用于单个检出结果或者做重复样品时结果的平均数（例如，直接平板法）。 When an acceptance criterion for microbiological quality is prescribed it is interpreted as follows: 给出的微生物质量接受标准解读如下： 101 CFU: maximum acceptable count = 20; 101 CFU: 最大可接受数 = 20; 102 CFU: maximum acceptable count = 200; 102 CFU: 最大可接受数 = 200; 103 CFU: maximum acceptable count = 2000； 103 CFU: 最大可接受数= 2000； Table 5.1.4.-1 includes a list of specified micro-organisms for which acceptance criteria are set. The list is not necessarily exhaustive and for a given preparation it may be necessary to test for other micro-organisms depending on the nature of the starting materials and the manufacturing process.表5.1.4-1给出了各种剂型的具体微生物接受标准。此表格并不完全，根据起始物料和生产工艺的性质可能需要其他的微生物检查。 If it has been shown that none of the prescribed tests will allow valid enumeration of micro-organisms at the level prescribed, a validated method with a limit of detection as close as possible to the indicated acceptance criterion is used. 若所有给出的测试方法都不能有效的测出描述微生物限度，需要使用其检测限尽可能接近接受标准的经过验证的方法。 In addition to the micro-organisms listed in Table 5.1.4.-1, the significance of other micro-organisms recovered is evaluated in terms of: 除了表5.1.4-1给出的微生物外，评估其他发现微生物的重要性要根据以下项目的评估： use of the product: hazard varies according to the route of administration (eye, nose, respiratory tract); nature of the product: its ability to support growth, the presence of adequate antimicrobial preservation; method of application; intended recipient: risk may differ for neonates, infants, the debilitated; use of immunosuppressive agents, corticosteroids; presence of disease, wounds, organ damage. Where warranted, a risk-based assessment of the relevant factors is conducted by personnel with specialised training in microbiology and the interpretation of microbiological data. For raw materials, the assessment takes account of processing to which the product is subjected, the current technology of testing and the availability of materials of the desired quality.-产品使用：根据使用途径不同危害不同（眼、鼻、呼吸道）；-产品的性质：促生长的能力，是否添加足量的防腐剂；-使用方法：-使用人群：新生儿、婴儿、体弱者；-免疫抑制剂、类固醇的使用；-有疾病、伤口、器官衰竭者；如果必要，应有受过专业微生物培训的人员对相关因素进行风险评估，并对微生物数据进行解读，对于原料药，评估要考虑其加工成制剂的工艺，目前的检验技术及能达到质量要求物料的可获得性。给药途径TAMC(CFU/g或CFU/ml)TYMC(CFU/g或CFU/ml)检测微生物非液体口服制剂103102不含大肠杆菌（1g或1ml）液体口服制剂102101不含大肠杆菌（1g或1ml）直肠给药103102口腔黏膜牙龈皮肤鼻腔耳道102101不含金黄色葡萄球菌（1g或1ml）不含铜绿假单胞菌（1g或1ml）阴道给药102101不含金黄色葡萄球菌（1g或1ml）不含铜绿假单胞菌（1g或1ml）不含白色念珠菌（1g或1ml）透皮贴剂（每帖包括黏胶层和后盖）102101不含金黄色葡萄球菌（每帖）不含铜绿假单胞菌（每帖）吸入剂（特殊要求适用于雾化用液体制剂）102101不含金黄色葡萄球菌（1g或1ml）不含铜绿假单胞菌（1g或1ml）不含可在胆汁存活的革兰阴性菌（1g或1ml）EP中特殊要求的对于口服固体制剂含自然来源（动物、植物或矿物）的原料，不适合抗菌处理时，以及监管机构接受原料TAMC超过103CFU/g或CFU/ml时104102可在胆汁存活的革兰阴性菌不得过102（1g或1ml）不含沙门氏菌（10ghuo10ml）不含大肠杆菌（1g或1ml）不含金黄色葡萄球菌（1g或1ml）TAMC(cfu/g或cfu/ml)TYMC(cfu/g或cfu/ml)药用物质103102