嘉峪检测网 2025-04-29 12:49
导读：近日，WHO在其技术报告TRS1060中发布了新的《药用辅料GMP》-2025，现将中英文翻译分享给大家。
近日，WHO在其技术报告TRS1060中发布了新的《药用辅料GMP》-2025，现将中英文翻译分享给大家：
Appendix 1
附录 1
Risk management in the production and control of excipients used in pharmaceutical products
制药产品中辅料的生产与控制中的风险管理
Introduction
引言
1.1 The WHO good manufacturing practices for excipients used in pharmaceutical products requires the application of risk management principles in the production, control and distribution of these excipients.
WHO关于制药产品中辅料的良好生产规范要求在辅料的生产、控制和分发过程中应用风险管理原则。
1.2 It is essential that manufacturers of these excipients assess the risks and identify hazards associated with the production and control and, when applicable, packaging, storage, repackaging and distribution of these excipients. This will enable manufacturers, packers and distributors to identify and to establish, implement and maintain controls as part of the quality system, to ensure the quality, safety and purity of excipients and their suitability for their intended use.
制造这些辅料的生产商必须评估生产过程中的风险和控制过程及相关风险(如适用,包括包装、储存、重新包装和分发),以确保生产商、包装商和分销商能够识别并建立、实施和维持质量管理体系中的控制措施,从而确保辅料的质量、安全性和纯度及其适合预期用途。
1.3 It may further assist manufacturers to identify, for example:
这还有助于生产商识别,例如:
whether separate, dedicated facilities are required for certain excipients;
是否需要为某些辅料专门设置独立的设施;
whether premises, equipment, instruments and utilities are suitable for their intended use in production and control of excipients;
是否需要确保厂房、设备、仪器和公用设施适合生产及控制辅料的预期用途；
what level and scope of qualification and validation is required;
需要进行何种程度的确认和验证;
whether there are any possible sources of contamination, including impurities;
是否存在任何可能的污染源,包括杂质;
what scope of documentation is required for the management of production and control of excipients;
需要何种范围的文件管理来管理和控制辅料的生产及控制；
whether subcontractors such as warehouses and transporters are suitable for distribution with no physical contamination.
是否需要合适的外包商(如仓库和运输商)进行分发,以确保无物理污染。
1.4 The extent and application of risk assessment may go beyond the above-mentioned examples to ensure continuous improvement in the facility.
风险评估的范围和应用可能超出上述示例,以确保设施的持续改进。
2.Scope
2.范围
2.1 This document provides guidance to manufacturers, packers and distributors of excipients used in pharmaceutical products, to identify risks and harms that may have a negative impact on the production, control, quality and purity of the excipient. It provides details in relation to the identification of potential contamination or cross - contamination risk of the excipients used in pharmaceutical products.
本文件为制药辅料制造商、包装商和分销商提供了指导,旨在识别可能对辅料的生产、控制、质量和纯度产生负面影响的风险和危害。文件详细介绍了制药产品中使用的辅料潜在污染或交叉污染风险的识别方法。
2.2 This document also provides useful information to manufacturers, packers and distributors on what to look for in their excipient suppliers.
本文件还为制造商、包装商和分销商提供了有关其辅料供应商应关注内容的实用信息。
3.Risk identification and risk assessment
3.风险识别与评估
3.1 There should be a document, such as a standard operating procedure, that describes the policy, approach and process of risk identification and risk assessment.
应有一份文件,如标准操作程序,描述风险识别和风险评估的政策、方法和流程。
3.2 The risk assessment should be performed in accordance with the principles described in guidelines such as the WHO guidelines on quality risk management (1) and ICH Q9 (2).
风险评估应遵循如世界卫生组织(WHO)质量风险管理指南(1)和国际 Conference on Harmonization(ICH)Q9(2)中所述的原则进行。
3.3 A suitable, appropriate risk assessment tool should be used by a multidisciplinary team performing the risk assessment. Failure mode and effects analysis (FMEA) and hazard analysis and critical control point (HACCP) are examples of such frequently used tools.
在进行风险评估时,应由多学科团队使用合适的、适当的评估工具。失效模式与效应分析(FMEA)和危害分析与关键控制点(HACCP)是常用的此类工具。
3.4 Although a quantitative or qualitative analysis can be done, quantitative assessments are recommended.
尽管可以进行定量或定性分析,但推荐进行定量评估。
3.5 The risk assessment should be thorough, comprehensive and appropriately documented. It should cover a variety of aspects, including raw materials, packaging materials, processing steps, solvents, equipment, utilities, environment, storage, distribution, intended use of the excipient, and the dosage form of the finished pharmaceutical product in which it may be used.
风险评估应全面、彻底,并适当记录。它应涵盖多个方面,包括原材料、包装材料、加工步骤、溶剂、设备、公用工程、环境、储存、分发、辅料的预期用途,以及可能使用该辅料的最终药物制剂。
3.6 A list of the potential risks (such as biological, chemical and physical) that may be introduced or increased in each area listed in paragraph 3.5 above should be identified and assessed.
应识别并评估在第3.5段中列出的每个区域可能引入或增加的潜在风险(如生物、化学和物理方面)。
3.7 In performing the risk assessment, the following basic questions (listed as examples) should be addressed:
在进行风险评估时,应回答以下基本问题(作为示例列出):
What might go wrong? (The use of “Why” may be useful.)
可能会发生什幺问题?(使用“为什幺”可能有助于分析。)
The materials, equipment, utilities or excipient (finished product) may be contaminated. The contaminants may be hazardous or may be sensitizing - and may be carried over into another product causing possible contamination. This may in turn result in an adulterated product, or may be harmful to patients consuming a pharmaceutical product that is contaminated with a material containing traces of such a substance.
原材料、设备、公用工程或辅料(最终产品)可能被污染。污染物可能是有害的,也可能是致敏性的,并可能转移到另一产品中造成污染。这可能会导致被篡改的产品,或者对使用含有此类物质痕迹的材料的药物产品进行服用的患者造成危害。
What is the nature of possible risks?
可能风险的本质是什幺?
The contaminants or material may be hazardous or poisonous and contaminate other materials, for example excipients, active pharmaceutical ingredients (APIs) or pharmaceutical products.
污染物或材料可能具有危害性或毒性,并可能污染其他材料,例如辅料、活性药物成分(API或药品。
What is the probability of contamination?
污染的可能性有多大?
Consider the chemical structure, manufacturing process, storage and distribution. Is it possible that materials can be substituted, mixed or otherwise contaminated? Can impurities form and be present? The probability should be evaluated with appropriate tools.
考虑化学结构、生产工艺、存储和分发等因素。材料是否有可能被替代、混合或其他方式污染?是否可能形成杂质并存在?应使用适当工具评估其可能性。
Is it possible to detect them?
是否能够检测到它们?
Contaminants, impurities and residues in materials may be present on equipment surfaces, in the environment, in solvents and in water. Carrier material may be difficult to remove. In addition, it may be difficult to analyse and quantify their presence unless appropriate, analytical procedures that are adequately sensitive are used.
材料中的污染物、杂质和残留物可能存在于设备表面、环境中、溶剂中或水中。载体材料可能难以去除。此外,除非使用足够灵敏的分析程序,否则可能难以分析和量化它们的存在。
What are the consequences (the severity)?
后果(严重性)是什幺?
Some impurities may cause harm and could even be carcinogenic and teratogenic.
某些杂质可能导致危害,甚至能致癌和致畸。
4.Individual excipient risk assessment
4.单独的辅料风险评估
4.1 Risk assessment should be done for every excipient produced. A checklist may be prepared and used to identify and assess risks and harms.
应对每种生产的辅料进行风险评估。可以准备并使用检查表来识别和评估风险及危害。
4.2 In assessing the risk, consideration should be given to the raw materials used, solvents used (fresh and recovered), premises (separated, segregated or in common), equipment (dedicated, disposable or not), water, environment and any other possible impacting factor.
在评估风险时,应考虑所使用的原料、溶剂(新鲜和回收的)、设施(分离、隔离或共用)、设备(专用、一次性或非一次性)、水、环境以及其他可能的影响因素。
4.3 Consideration should be given to the possible toxicity of the excipient (for example, when contaminated or can contaminate), the risk of the excipient being contaminated, adulterated or cross - contaminated, cleanability of equipment, presence of impurities, and degradation, where applicable.
应考虑辅料的潜在毒性(例如,当受污染或能污染时)、辅料受污染、掺假或交叉污染的风险、设备的清洁性、杂质的存在、以及适用时的降解问题。
4.4 The risk of contaminated solvents being used in the synthesis should be assessed.
应评估在合成过程中使用受污染溶剂的风险。
4.5 The risk of formation of impurities should be assessed.
应评估杂质形成的风险。
5.Collective excipient production assessment
5.集体制剂辅料生产评估
5.1 In addition to individual excipient risk assessment as described above, where several excipients are produced or packed in the same facility, the risk of contamination should be identified and assessed. In particular, where a risk has been identified in one or more excipients handled in the same facility or common equipment chains, the risk of cross - contamination should be assessed.
除上述对单个辅料进行的风险评估外,如果多个辅料在同一设施中生产或包装,应对这些辅料的生产风险进行综合评估。污染应当被识别和评估。特别是在同一设施处理的一种或多种辅料中已识别出风险,或在共用设备链中存在风险时,应当评估交叉污染的风险。
6.Nitrosamine contamination
6.硝酸胺污染
6.1 Although very few excipients can form nitrosamine impurities, the risk of nitrosamine formation or contamination should be identified and assessed. For example, nitrite in potable water used in production and present in the environment, packaging materials or ink should be considered (3, 4).
尽管很少有辅料能够形成氮胺杂质,但仍应识别和评估氮胺形成或污染的风险。例如,生产过程中使用的饮用水中的亚硝酸盐以及环境、包装材料或油墨中的亚硝胺应予以考虑(3, 4)。
7.Example
7.示例
7.1 The example below follows a similar approach to FMEA.
以下示例遵循类似FMEA的方法。
7.2 Risk statement: Are the premises appropriately designed, located and maintained for the manufacture of excipients used in pharmaceutical products?
风险声明:生产场所是否设计、定位和维护得当,以适于制造用于制药产品的辅料?
7.3 Risk statement: Are pieces of equipment appropriately designed, located and maintained for the manufacture of excipients used in pharmaceutical products?
风险声明:用于制药产品的辅料制造的设备是否设计、布置和维护得当?
7.4 Risk statement: Are the materials used in the production of the excipient of appropriate quality and purity, or is there a risk of formation of impurities and undesired contaminants that may be present in pharmaceutical products?
风险声明:生产辅料所用的材料是否具有适当的品质和纯度,是否存在形成杂质和非预期污染物的风险,这些杂质和污染物可能存在于药品中?
7.5 Risk statement: Are the utilities appropriately designed, located, maintained and controlled to prevent contamination of material, and prevent the risk of the formation of impurities and contaminants?
风险声明:设施是否设计、布局、维护和控制得当,以防止材料污染,并防止杂质和污染物的形成风险?
7.6 Risk statement: Are the personnel appropriately trained and qualified to ensure that their actions and conduct do not present a risk of contamination of materials?
风险声明:相关工作人员是否得到了适当的培训和资质认证,以确保其行为和行为规范不会对材料造成污染的风险?
7.7 Risk statement: Is the production process appropriately developed and controlled to ensure that interaction between materials, or any step in production and purification, will not result in contamination of the excipient, resulting in a material of unacceptable quality and purity?
风险声明:生产工艺是否已适当开发和控制,以确保材料之间的相互作用或生产工艺和纯化过程中的任何步骤不会导致辅料受到污染,从而产生不符合质量与纯度要求的物料?
7.8 Risk statement: Is the repackaging process appropriately controlled to prevent any risk of contamination, mix - up or substitution of materials that may result in a material of unacceptable quality and purity?
风险声明:重新包装过程是否得到了适当控制,以防止任何可能造成材料质量或纯度不符合要求的风险,包括污染、混淆或替换材料?
7.9 Risk statement: Is the storage process appropriately controlled, in accordance with storage requirements, to prevent any risk of uncontrolled degradation, increase in level of impurity, contamination, mix - up or substitution of materials that may result in a material of unacceptable quality and purity?
风险声明:存储过程是否得到了适当控制,以符合存储要求,从而防止任何由于未经控制的降解、杂质水平增加、污染、物料混用或替代而导致的不合格物料和不纯物质的风险?
7.10 Risk statement: Is the distribution process appropriately controlled, in accordance with good practices, to prevent any risk of uncontrolled degradation, increase in level of impurity, contamination, mix - up or substitution of materials that may result in a material of unacceptable quality and purity?
风险声明:分发过程是否按照良好实践适当控制,以防止任何由于未经控制的降解、杂质水平增加、污染、物料混用或替代而导致的不符合质量与纯度要求的物料的风险?
8.Risk control
8.风险控制
8.1 Once risks and harms have been identified and assessed, controls should be identified to mitigate the risks and harms.
一旦识别并评估了风险和危害,应确定相应的控制措施以减轻这些风险和危害。
8.2 Controls should be proven to be effective.
控制措施应被证明是有效的。
9.Risk communication
9.风险沟通
9.1 Risks and controls should be appropriately communicated to the relevant personnel or interested parties.
风险和控制措施应适当地向相关人员或利益相关方进行沟通。
10.Risk review
10.风险审查
10.1 Risk assessment and risk controls should be reviewed when changes are considered, for example, introduction of new excipients or products to the facility, changes in manufacturing process, changes in equipment, or change in suppliers of materials and solvents.
当考虑进行变更时,例如引入新的辅料或产品、生产工艺变更、设备变更或原材料和溶剂供应商变更,应审查风险评估和风险控制措施。
10.2 Risk review may be done periodically, and when a change has been made (as listed in section 10.1 above), to ensure that the mitigating tools are still effective and the risk has not changed or increased.
风险审查应定期进行,并在上述第3节所列的变更发生时进行,以确保减轻工具仍然有效,且风险没有发生变化或增加。
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