「英中对照」Cormica解析制药职业卫生与替代分子的作用

Within the pharmaceutical industry, this includes the routine monitoring of active pharmaceutical ingredients (APIs), relevant excipients and surrogate materials through air filter sampling and surface swabbing. Samples are analysed against established occupational exposure limits (OELs) using validated, highly sensitive, robust analytical methods to assess operator exposure and verify the effectiveness of exposure controls.在制药行业中，这包括通过空气过滤器采样和表面擦拭，对活性药物成分（API）、相关辅料和替代材料进行常规监测。采用经过验证、高灵敏度且稳健的分析方法，依据既定的职业接触限值（OEL）对样品进行分析，以评估操作人员的暴露情况并验证暴露控制措施的有效性。

Cormica specialises in the development, validation and deployment of analytical methods for monitoring occupational exposure to pharmaceutical APIs in manufacturing, clinical and laboratory environments. Our expertise supports clients in protecting employee health, demonstrating the effectiveness of engineering and procedural controls, and maintaining compliance with applicable regulatory requirements and industry guidance.Cormica 专注于开发、验证和部署用于监测生产、临床和实验室环境中药物 API 职业暴露的分析方法。我们的专业知识支持客户保护员工健康、证明工程和程序控制措施的有效性，并保持符合适用的法规要求和行业指南。

1) Cormica’s approach1) Cormica 的方法

Pharmaceutical environments require a more rigorous approach than generic COSHH compliance alone. Occupational hygiene programmes should be underpinned by risk assessments aligned with GMP/GXP principles, occupational exposure banding frameworks, containment strategies and robust, documented justification of exposure control measures. This integrated approach helps ensure both regulatory compliance and the safe manufacture and handling of pharmaceutical products.制药环境需要比单纯的一般 COSHH 合规更为严格的方法。职业卫生计划应以符合 GMP/GXP 原则的风险评估、职业暴露分级框架、密闭策略以及稳健且有文件记录的暴露控制措施论证为支撑。这种综合方法有助于同时确保法规合规性以及药品的安全生产和操作。

Establishing an occupational hygiene monitoring programme is a complex, multi-faceted undertaking. Our holistic OH package guides you through every step, including the development and validation of analytical methods for multiple active ingredient types (hormones, cytotoxics, antibiotics and controlled drug substances):建立职业卫生监测计划是一项复杂且涉及多方面的工作。我们的整体 OH 方案将指导您完成每一个步骤，包括针对多种活性成分类型（激素、细胞毒性药物、抗生素和管制药物）的分析方法开发与验证：

• Support in OH risk assessment, limit setting, sampling/testing protocols在 OH 风险评估、限值设定、采样/检测方案方面提供支持
• Sensitive analytical methods suitable for multiple analytes, meeting the growing demand for particularly challenging OEL/reporting limits适用于多种分析物的灵敏分析方法，满足对极具挑战性的 OEL/报告限值日益增长的需求
• Preparation and supply of media (swabs, filters and pre-loaded IOM cassettes); training your staff in effective sampling techniques介质的制备与供应（拭子、过滤器和预装 IOM 采样盒）；为您的员工提供有效采样技术培训
• Routine analysis of samples with fast turnaround times样品的常规分析，周转时间短
• Analytical method development, validation and testing of proprietary APIs, as well as surrogate API materials such as lactose, mannitol and naproxen sodium专有 API 的分析方法开发、验证和测试，以及乳糖、甘露醇和萘普生钠等 API 替代材料

The process is typically broken down into the following steps:该流程通常分为以下几个步骤：

Figure 1: Occupational Hygiene Workflow图 1：职业卫生工作流程

2) Why and how do we swab?2) 我们为什么以及如何进行擦拭采样？

Surface swabbing, along with air sampling, is the preferred method for monitoring the presence of potentially hazardous species within the manufacturing environment for both occupational hygiene and cleaning validation/verification. Potential contaminants are recovered by swabbing, eluted from the swab using a carefully selected diluent, and then tested down to trace levels. As a result, the selection of a high-quality swab and the development of a validated detection method (e.g. HPLC-UV, LC-MS, TOC, ICP-MS) are critical to producing sensitive, accurate and repeatable results.表面擦拭与空气采样相结合，是职业卫生和清洁验证/确认中监测生产环境内潜在有害物质存在的首选方法。潜在污染物通过擦拭回收，使用精心选择的稀释剂从拭子上洗脱，然后检测至痕量水平。因此，选择高质量的拭子并开发经过验证的检测方法（如 HPLC-UV、LC-MS、TOC、ICP-MS）对于获得灵敏、准确且可重复的结果至关重要。

Swabs must offer:拭子必须具备：

• Minimal extractable interferences极低的可提取物干扰
• High analyte recovery rates高分析物回收率
• Ultra-low particle/fibre generation超低颗粒/纤维产生

They should be compatible with the desired swabbing diluent and the chosen analytical technique, which in turn should be suitable for the surfaces being swabbed and the analyte to be recovered. It is also very important to include field blank swab and air filter sampling as controls.它们应与所需的擦拭稀释剂和所选的分析技术相兼容，而分析技术又应适用于被擦拭的表面和待回收的分析物。同样非常重要的是，应将现场空白拭子和空气过滤器采样作为对照。

It should be noted that recovery rates are a function of the swabbing methodology, as well as the material absorption and residue-releasing attributes of the swab. The effective use of a robust swabbing pattern is critical to ensure accurate and reproducible collection of residues.应当注意，回收率取决于擦拭方法，以及拭子的材料吸附和残留物释放特性。有效采用稳健的擦拭模式对于确保准确且可重现地采集残留物至关重要。

An example of a recommended swabbing pattern, employing two swabs, is shown below. Once the surface has been swabbed, the used swab heads should be promptly placed in the extraction solvent, according to the validated procedure.下面展示了一个使用两支拭子的推荐擦拭模式示例。表面擦拭完成后，应按照经过验证的程序，立即将使用过的拭子头放入提取溶剂中。

Figure 2: Swab sampling pattern图2：拭子采样模式

3) Why use a surrogate?3) 为什么使用替代物？

A surrogate is a low-toxicity material that can replace an active pharmaceutical ingredient (API) when the use of the API is not advisable due to safety concerns. Surrogates are used to simulate potential emissions or sampling for analytical methods, ensuring compliance with safety regulations. They are essential for assessing workplace exposure to hazardous substances and maintaining a safe working environment.替代物是一种低毒性材料，当出于安全考虑不宜使用原料药（API）时，可用其代替API。替代物用于模拟潜在的排放或分析方法采样，确保符合安全法规。它们对于评估工作场所对有害物质的暴露以及维持安全的工作环境至关重要。

The use of a surrogate is common when performing both cleaning validation and occupational hygiene studies. In a multi-product site, such as one operated by a CDMO (Contract Development and Manufacturing Organization), it may not be possible to know or predict the worst-case scenario API with which to undertake the OH evaluation. Also, the API may be in short supply, expensive or highly potent. In these cases, it is possible to justify the use of a surrogate API.在进行清洁验证和职业卫生研究时，使用替代物很常见。在多产品场地，例如由CDMO（合同开发与生产组织）运营的场地，可能无法知道或预测用于开展职业卫生（OH）评估的最差情形API。此外，API可能供应短缺、价格昂贵或具有高活性。在这些情况下，可以合理地使用替代API。

Naproxen sodium is a common surrogate used throughout the industry. It is regarded as safe and non-potent, has good detectability using UV and fluorescence detectors, demonstrates a high level of dustiness, which is required for occupational hygiene studies, and is inexpensive and readily available.萘普生钠是行业内常用的替代物。它被认为是安全且无高活性的，使用紫外和荧光检测器具有良好的可检测性，表现出较高的粉尘飞扬性（这是职业卫生研究所需的），并且价格低廉、易于获得。

An additional advantage of using a surrogate for this purpose is that a single validated analytical procedure can be applied to multiple manufacturing and sampling scenarios, with relatively minor additional development and validation required to take account of the specific facility or process being evaluated (e.g. bespoke surfaces).为此目的使用替代物的另一个优点是，单一经过验证的分析程序可应用于多种生产和采样场景，只需相对较少的额外开发和验证即可考虑所评估的特定设施或工艺（例如定制表面）。

4) Naproxen sodium methodology4) 萘普生钠方法

Cormica’s in-house naproxen sodium method has been developed to offer excellent sensitivity, linear range and run time/efficiency (see Table 1) for testing both swabs and air filters. The method can be adapted to your specific requirements, and Cormica can work with you to determine carryover limits if these are not already known. Swab recovery factors can be determined for your specific surfaces and used for your occupational hygiene or cleaning validation study.Cormica内部的萘普生钠方法经过开发，可为拭子和空气过滤器的检测提供出色的灵敏度、线性范围和运行时间/效率（见表1）。该方法可根据您的具体要求进行调整，如果残留限值尚不明确，Cormica可以与您合作确定。可以针对您的特定表面测定拭子回收因子，并用于您的职业卫生或清洁验证研究。

The linearity and sensitivity are well established for this method; hence, only minimal additional validation would be required to support the bespoke aspects of your study.该方法的线性和灵敏度已得到充分确立；因此，只需极少的额外验证即可支持您研究中的定制方面。

Figure 3: In-house naproxen HPLC method – linear range图 3：内部萘普生 HPLC 方法——线性范围

Naproxen sodium is a highly suitable surrogate for manufacturing support studies where the assessment of a product-specific API is not practical. In addition to in-house, validated methods for mannitol and lactose, Cormica has developed and validated a sensitive, efficient and cost-effective method for the quantification of naproxen sodium in support of occupational hygiene and cleaning validations.萘普生钠是一种高度适用的替代物，适用于对产品特异性 API 进行评估并不现实的生产支持研究。除甘露醇和乳糖的内部验证方法外，Cormica 还开发并验证了一种灵敏、高效且具有成本效益的方法，用于萘普生钠的定量分析，以支持职业卫生和清洁验证。

Where the use of a surrogate such as naproxen sodium is not appropriate or not desired, Cormica can also support clients with bespoke analytical methods for their specific API or group of APIs. With detection capabilities such as UV, FLD, MS, MS/MS and CAD, we can provide support even where sensitivity and specificity are challenging.当使用萘普生钠等替代物不合适或并非所需时，Cormica 还可以为客户针对其特定的 API 或 API 组合提供定制分析方法的支持。凭借 UV、FLD、MS、MS/MS 和 CAD 等检测能力，即使在灵敏度和特异性具有挑战性的情况下，我们也能提供支持。