USP37 <1111>非无菌药品微生物检查：药用制剂和药用物质可接受标准（中英文）

<1111> MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: ACCEPTANCE CRITERIA FOR PHARMACEUTICAL PREPARATIONS AND SUBSTANCES FOR PHARMACEUTICAL USE

非无菌药品微生物检查：药用制剂和药用物质可接受标准

The presence of certain microorganisms in nonsterile 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 have therefore 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.

在非无菌制剂中如果出现特定的微生物，可能会降低甚至失去治疗活性，对患者健康产生潜在负面影响。因此，生产商需要通过在生产、存贮制剂的过程中实施GMP现行指南，保证制剂的生物负载在一个较低的水平。

Microbial examination of nonsterile products is performed according to the methods given in the texts on Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62 . Acceptance criteria for nonsterile pharmaceutical products based upon the total aerobic microbial count (TAMC) and the total combined yeasts and molds count (TYMC) are given in Tables 1 and 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).

非无菌药品的微生物检查应根据<61 微生物限度检查>和<62 控制菌测试>进行。非无菌药品的可接受标准根据表1和表2中给定的“总有氧菌计数TAMC”和“总酵母菌和霉菌计数TYMC”进行判定。是否符合可接受标准应基于单个结果或基于重复计数（例如，平皿法）的平均结果来进行判定。

When an acceptance criterion for microbiological quality is prescribed, it is interpreted as follows:

如果指明了微生物质量的可接受标准，则含义如下

—      101 cfu: maximum acceptable count = 20;

—      101cfu：最大可接受计数 =20

—      102 cfu: maximum acceptable count = 200;

—      102cfu：最大可接受计数 =200

—      103 cfu: maximum acceptable count = 2000; and so forth.

—      103cfu：最大可接受计数 =2000

Table 1. Acceptance Criteria for Microbiological Quality of Nonsterile Dosage Forms

表1 非无菌制剂微生物质量可接受标准

Route of Administration 摄入途径	Total Aerobic Microbial Count 总有氧菌计数 (cfu/g or cfu/mL)	Total Combined Yeasts/Molds Count 总酵母菌和霉菌计数 (cfu/g or cfu/mL)	Specified Microorganism(s) 控制菌
Nonaquesous preparations for oral use	103	103	Absence of Escherichia coli (1g or 1 mL)
口服非水性制剂	103	103	大肠杆菌不得检出（1g或1ml）
Aqueous preparations for oral use	102	101	Absence of Escherichia coli (1g or 1 mL)
口服水性制剂	102	102	大肠杆菌不得检出（1g或1ml）
Rectal use	103	102	--
直肠用药	103	102	---
Oromucosal use	102	101	Absence of Staphylococcus aureuginosa (1g or 1mL)
口腔给药	102	101	金葡菌不得检出（1g或1ml）
Gingival use	102	101	Absence of Staphylococcus aureus (1g or 1mL) Absence of Pseudomonas aeruginosa (1g or 1 mL)
齿龈给药	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml）
Cutaneous use	102	101	Absence of Staphylococcus aureus (1g or 1mL) Absence of Pseudomonas aeruginosa (1g or 1 mL)
皮肤给药	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml）
Nasal use	102	101	Absence of Staphylococcus aureus (1g or 1mL) Absence of Pseudomonas aeruginosa (1g or 1 mL)
经鼻给药	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml）
Auncular use	102	101	Absence of Staphylococcus aureus (1g or 1mL) Absence of Pseudomonas aeruginosa (1g or 1 mL)
经耳给药	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml）
Vaginal use	102	101	Absence of Staphylococcus aureus (1g or 1mL) Absence of Pseudomonas aeruginosa (1g or 1 mL) Absence of Candida albicans (1g or 1 mL)
阴道给药	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml） 白色念珠菌不得检出（1g或1ml）
Transdemal patches (limits for one patch including adhesive layer and backing)	102	101	Absence of Staphylococcus aureus (1 patch) Absence of Pseudomonas aeruginosa (1 patch)
透皮贴剂（限于背衬和粘剂在同一层）	102	101	金葡菌不得检出（1帖） 铜绿假单胞菌不得检出（1贴）
Inhalation use (special requirements apply to liquid preparations for nebulization).	102	101	Absence of Staphylococcus aureus (1 g or 1 mL) Absence of Pseudomonas aeruginosa (1 g or 1 mL) Absence of bile-tolerant Gram-negative bacteria (1 g or 1 mL)
吸入剂（喷雾用液体制剂适用特殊要求）	102	101	金葡菌不得检出（1g或1ml） 铜绿假单胞菌不得检出（1g或1ml） 革兰阴性菌不得检出（1g或1ml）

Table 1 includes a list of specified microorganisms 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 microorganisms depending on the nature of the starting materials and the manufacturing process.

表1包括控制菌清单及所设定的可接受标准。清单并未列出所有控制菌，对于特定的制剂，可能需要根据起始物料和生产工艺的特性检测其它微生物。

If it has been shown that none of the prescribed tests will allow valid enumeration of microorganisms at the level prescribed, a validated method with a limit of detection as close as possible to the indicated acceptance criterion is used.

如果已经证明指定测试均不能在指定水平获得有效微生物计数，则应采用一个与指定的可接受标准尽可能接近的经过验证的方法进行测试。

Table 2. Acceptance Criteria for Microbiological Quality of Nonsterile Substances for Pharmaceutical use

表2 非无菌药用物质的微生物质量可接受标准

	Total Aerobic Microbial Count 总有氧菌计数 (cfu/g or cfu/mL)	Total Combined Yeasts/Molds Count总酵母菌/霉菌计数 (cfu/g or cfu/mL)
Substances for pharmaceutical use 药用物质	103	102

In addition to the microorganisms listed in Table 1, the significance of other microorganisms recovered should be evaluated in terms of the following:

除了表1中所表明的微生物以外，其它微生物的重要性要根据以下情况评估：

l         The use of the product: hazard varies according to the route of administration (eye, nose, respiratory tract).

l         产品的用途：根据摄入途径其毒性不同（由眼、鼻、呼吸途径）

l         The nature of the product: does the product support growth? does it have adequate antimicrobial preservation?

l         产品的特性：是否有益细菌滋生？是否具有充分的防腐性？

l         The method of application.

l         应用方法

l         The intended recipient: risk may differ for neonates, infants, the debilitated.

l         新生儿、婴儿和体弱者的受者风险可能会不同

l         Use of immunosuppressive agents, corticosteroids.

l         使用了免疫抑制剂、激素类药物

l         The presence of disease, wounds, organ damage.

l         有疾病、外伤或器官损伤时

Where warranted, a risk-based assessment of the relevant factors is conducted by personnel with specialized training in microbiology and in the interpretation of microbiological data. For raw materials, the assessment takes account of the processing to which the product is subjected, the current technology of testing, and the availability of materials of the desired quality.

如果能保证质量，可以由一个接受过微生物专业和微生物数据诠释培训的人员对相关因素进行基于风险的评估。对于原料，评估应考虑产品所经过的处理、现行检测技术，以及该原料所能获得的质量水平。

Auxiliary Information – Please check for your question in the FAQs before contacting USP.

Topic/question	Contact	Expert Committee
General Chapter	Radhakrishna S Tirumalai, Ph.D Principal Scientific Liaison (301)816-8339	(GCM2010)General Chapters-Microbiology

USP 37-NF32 Page 923

Pharmacopeial Forum : Volume No. 29(5) Page 1733

好资料，谢谢楼主的分享