With the new chapter on Contamination Control Strategy (CCS), the USP builds a bridge between the requirements of CFR and the current 1st edition. In its introduction, the USP states that microbiological contamination control is a crucial part of drug manufacturing. In the USA, this is regulated by legal requirements such as CFR §211.113. A contamination control strategy (CCS) is required to minimise the risk of microbial contamination. It includes a holistic view of the entire production facility and is based on quality risk management (QRM). The most important sections are listed below, whereby the USP emphasises that this overview does not represent a 100% list of all relevant aspects.

 

近日，USP发布了关于污染控制策略 （CCS） 的新章节。USP 在其介绍中指出，微生物污染控制是药物生产的关键部分。需要制定污染控制策略 （CCS） 以最大限度地降低微生物污染的风险。它包括整个生产设施的整体视图，并基于质量风险管理 （QRM）。下面列出了最重要的部分，USP 强调，本概述并不代表所有相关方面的 100% 列表。

 

 

Planning and operation of the plant

 

厂房设计和运行

 

Cleanroom design: minimisation of microbial contamination through cascading pressurisation and appropriate cleanroom classifications (ISO standards).

洁净室设计：通过压差梯度和适当的洁净室分类（ISO标准）最大限度地减少微生物污染。

Air control systems: Temperature, ventilation and humidity control, use of HEPA filters.

空气控制系统：温度、通风和湿度控制，使用 HEPA 过滤器。

Material flow & process flow: Unidirectional processes to avoid      cross-contamination.

物流和工艺流：单向过程以避免交叉污染。

Cleanroom qualification: Regular testing of particles, airflow and filter integrity.

洁净室确认：定期测试颗粒、气流和过滤器完整性。

Maintenance: Planning of building maintenance taking microbial risks into account.

维护：厂房维护计划考虑微生物风险

 

Equipment and process

 

设备和工艺

 

Equipment design: Cleanable and sterilisable production equipment with validated cleaning efficiency.

设备设计：可清洁和可消毒的生产设备，清洁有效性经过验证。

Process design: Closed systems are preferred; open processes require ISO 5 environment.

工艺设计：首选密闭系统;开放式工艺需要 ISO 5 环境。

Material transfer: Validated methods for transfers to ISO 5 areas.

物料转移：使用经过验证的方法转移到 ISO 5 区域。

Hold times: Must be validated to prevent microbial growth.

保持时间：应验证以防止微生物生长。

 

Personnel

 

人员

 

Training: Fundamentals of microbiology, aseptic technique, environmental controls and cleaning.

培训：微生物学基础知识、无菌技术、环境控制和清洁。

Garbing: ISO 8 areas require protective suits, ISO 5 areas require additional sterile bonnets, masks and gloves.

着装：ISO 8 区域需要防护服，ISO 5 区域需要额外的无菌头罩、口罩和手套。

Qualification: Includes training, monitoring and microbiological testing.

确认：包括培训、监测和微生物测试。

 

Supply facilities

 

公用设施

 

Water: Must be pharmaceutical grade and regularly tested for microbial contamination.

水：必须是制药级的，并定期进行微生物污染检测。

Process gases: Direct contact with products requires sterile filters (0.2 µm) and regular testing.

工艺气体：与产品直接接触需要除菌过滤器 （0.2 μm） 并定期测试。

 

Raw material controls

 

原辅料控制

 

Risk assessment: Takes into account origin, manufacturing processes and storage.

风险评估： 考虑源头、生产工艺和储存。

Incoming inspections: Inspection of materials by suppliers and manufacturers required.

入厂检验： 需要供应商和制造商对物料进行检验。

 

Product containers and closures

 

产品容器和密封部件

 

Integrity assurance: Container and closure integrity testing.

完整性保证：容器和密封部件完整性测试

Storage and transport validation: Ensuring microbial barrier function.

储存和运输验证：确保微生物屏障功能。

 

Management of outsourcing activities

 

外包活动管理

 

Quality assurance of external service providers: audits, quality agreements and regular inspections.

外部服务提供商的质量保证：审计、质量协议和定期检查。

Examples: Sterilisation, environmental monitoring and cleaning of outsourced areas.

示例：外包区域的清洁、消毒和环境监测。

 

Risk management and process validation

 

风险管理和工艺验证

 

QRM approach: Identifying, analysing and assessing microbial risks.

QRM

方法：识别、分析和评估微生物风险。

Process validation: Continuous evaluation of sterilisation and production processes.

工艺验证：对灭菌和生产过程进行持续评估。

 

Cleaning and disinfection

 

清洁和消毒

 

Regular disinfection: Based on cleanroom classification and microbial trends.

定期消毒：基于洁净室级别和微生物趋势。

Validation: Documentation of the effectiveness of cleaning agents and disinfectants used.

验证：记录所用清洁剂和消毒剂的有效性。

 

Verification of monitoring controls

 

监测措施的确认

 

Environmental and personnel monitoring: Evaluation of microbial control in production areas.

环境和人员监测：生产区域微生物控制评估。

Alternative monitoring methods: Faster detection of contamination using new technologies.

替代监测方法：使用新技术更快地检测污染。

Trend analyses: To identify microbial hotspots and optimise the CCS.

趋势分析：识别微生物热点并优化 CCS。

 

Aseptic process simulations (APS)

 

无菌工艺模拟（APS）

 

Regular tests: Worst-case scenarios to ensure aseptic conditions.

定期测试： 在最差条件下测试以确保无菌条件

Validation of media fill tests: Proof of the effectiveness of the aseptic process.

培养基灌装测试验证：无菌工艺有效性的证明。

 

Investigation of deviations

 

偏差调查

 

Root cause analysis: Determining the cause of microbial contamination.

根本原因分析：确定微生物污染的原因。

Corrective and preventive actions (CAPA): Implementation and effectiveness testing.

纠正和预防措施 （CAPA）：实施和有效性测试。

 

 

来源：Internet

关键词： 污染控制策略