FDA对江苏翰森制药无菌药品生产发出OAI 483，提出七项观察

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受检机构/公司：Jiangsu Hansoh Pharmaceutical Group Co Ltd.

类型：Sterile Drug Manufacturer无菌药品生产

FEI号：3008316144

检查员：

Karen A Briggs, Investigator
Sandra A Boyd, Investigator

检查日期：2026-04-16 至 2026-04-24

为了帖子不下架，全文无吐槽，仅介绍下 sandra

Sandra Boyd的介绍，她 是美国食品药品监督管理局（USFDA）药品质量项目分支的药品国家专家（FDA技术最高职称）。她于 2009 年开始在 FDA 的职业生涯，担任调查员，负责在美国以及国际范围内进行复杂的药品检查。她曾在国外药品质量部门（foreign cadre）工作了四年，并在北京的中国办公室担任过详细工作。目前，Sandra 的时间一半用于进行检查，另一半用于培训新调查员进行无菌检查及数据完整性方面的培训。在加入 FDA 之前，她在制药行业工作了 17 年，最后的职位是某原料药制造商的质量与监管总监。此外，boyd应该是她的夫姓，在FDA工作的头几年，她用的是原名。业内一直盛传他是杀手级检查员justin Boyd的媳妇，也是源于此。

观察项 1 / Observation 1

旨在防止声称无菌的药品发生微生物污染的程序，未包含对灭菌工艺的充分验证。具体如下：

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the sterilization process. Specifically,

A. 烟雾源未经验证 / Source of smoke not validated

无法提供科学证据证明你方在气流流型可视化研究（烟雾试验）中所用烟雾的来源呈中性浮力。在对 xxx 车间及 xxx 线的无菌灌装线进行烟雾试验视频回顾时，发现以下不一致之处：

A. Scientific evidence could not be provided demonstrating the source of the smoke used during your air flow visualization studies is neutrally buoyant. During your review of smoke study videos in your aseptic filling lines in workshops xxx as well as the xxx line, the following discrepancies were noted:

1. xxx 型 RABS 的 xxx 风管相对于 B 级区的设置位置存在使 B 级气流短路的可能，从而导致洁净室内产生向上气流。该区域未开展烟雾试验以证明无菌灌装线各车间气流充分。

2. 气流视频录制时烟雾垂直向上喷出，未能形成可评估气流状况的均匀烟雾帘幕。

3. 多段烟雾试验视频中观察到湍流现象，但在你方审核和批准过程中未对这些湍流进行评估或说明。

4. 作业发生区域未施放烟雾；此外，观察发现烟雾快速消散，降低了探测涡流和不良气流的能力。

5. 当 RABS xxx 处于 xxx 状态时，首层气流无法到达产品接触表面。

1. The positioning of the xxx ducts of the xxx RABS in relation to the grade B area has the potential to short circuit the grade B air flow, causing an upward movement of air in the cleanroom. Smoke studies have not been performed in this area to demonstrate adequate airflow in aseptic filling lines workshops xxx

2. Air flow videos are recorded with the smoke pointing directly upwards, not providing a uniform curtain of smoke in which to evaluate air currents.

3. Turbulence was noted in various smoke study videos which were not assessed or addressed during the firm’s review and approval.

4. Smoke is not present where activities are taking place. Additionally, rapid dissipation of smoke was noted which reduces the ability to detect eddy currents and adverse airflow.

5. When the RABS xxx is xxx, first air does not reach the product contact surfaces.

B. 培养基模拟灌装不能代表商业化生产 / Media fills not representative

培养基模拟灌装（培养基灌装）不能代表商业化生产：模拟灌装中仅模拟了干预的持续时间，而未模拟实际操作动作。例如，xxx 车间 xxx ml 西林瓶培养基模拟灌装验证方案 C-VP-206-026000-2541 要求模拟灌装线维护作业。2025年10月17日，维护人员在 RABS 内部进行了一项操作，时长约 xxx，随后携带 xxx 在 RABS 旁站立了剩余的 xxx。在此期间该操作人员未执行任何其他操作，却通过此次培养基模拟灌装被认定为合格。

B. Media fills are not representative of commercial manufacturing. Only the duration of an intervention is simulated in a media fill and not the physical activities. For example, C-VP-206-026000-2541 Validation Protocol of Media Fill for xxx ml vial in workshop xxx requires a xxx simulation of maintenance in the filling line. On 17Oct2025, the maintenance personnel performed an activity inside the RABS for approximately xxx then remained standing xxx the RABS with the xxx for the remaining xxx The operator did not perform any additional activities during this time and was considered qualified by this media fill.

C. 去污染验证不充分 / Decontamination validation inadequate

你方针对无菌生产区域的 xxx 去污染验证未经过充分验证，未能证明所有关键表面均得到有效灭菌/去污。

C. Your firm’s xxx decontamination validation for aseptic processing areas has not been adequately validated to demonstrate effective sterilization of all critical surfaces.

1. xxx 设计存在缺陷：xxx 车间 xxx 被观察到存在 xxx 现象，从而形成未完全暴露于 xxx 的遮挡区域；xxx 车间 xxx 未 xxx，所观察到的 xxx 未 xxx；此外，在 xxx 过程中 xxx 未被 xxx。你尚未评估 xxx 的 xxx 区域的 xxx 效力。

1. Deficient xxx design

• Workshop xxx xxx were observed. xxx xxx Thus creating areas of occlusion not fully exposed to xxx

• Workshops xxx xxx do not xxx xxx observed were not xxx Additionally, xxx were not xxx during xxx process.

• You have not evaluated the xxx efficacy in xxx areas of the xxx

2. xxx 灭菌保证不充分：xxx 在初次安装前处于 xxx 状态；无法保证日常去污染循环期间 xxx 被完全且均匀地覆盖。

2. Inadequate xxx sterilization assurance

• xxx are xxx, prior to initial installation

• There is no assurance that xxx are completely and uniformly covered by the xxx during routine decontamination cycles

3. 验证文件不完整：验证方案和报告中均无 xxx 循环期间留在房间内的设备清单；验证方案和报告中对生物指示剂（BI）和化学指示剂的具体放置位置没有形成文件记录。

3. Incomplete validation documentation

• There is no list of equipment that remains in the room during xxx cycle, in the validation protocol or in the report

• There is no documentation on specific locations of BI and chemical indicators placement within the validation protocol and report

在 xxx 车间生产并销往美国市场的产品包括 xxx。

US marketed products manufactured in Workshop xxx include xxx

xxx

D. 未定义培养基模拟灌装期间的固有/纠正性干预 / No defined interventions for operator qualification

对于无菌灌装操作人员，没有定义其在培养基模拟灌装期间须执行的固有（常规）或纠正性干预项目以证明其操作资质。例如，文件显示 xxx 名操作人员在商业化生产期间执行生产前准备工作（setup）。其中一名操作人员负责设备准备工作，包括无菌连接；其余操作人员协助向主操作人员传递设备。批记录中未区分主操作人员与辅助操作人员。培养基模拟灌装也以相同方式处理，无从确定谁（xxx）执行了无菌连接。这导致无法保证在商业化生产中执行准备工作的操作人员此前曾在培养基模拟灌装中成功完成过同样的准备工作。

D. There are no defined inherent or corrective interventions to be performed during a media fill in order to be qualified as an aseptic filling operator. For example, xxx operators are documented as performing setup during commercial manufacturing. One operator performs the setup of the equipment, including aseptic connections, while the remaining operators assist by passing equipment to the main operator. In the batch record, there is no differentiation between the main operator and the support operators. Media fills are handled the same way with no way to determine who the support operators were xxx who performed the aseptic connection. This results in no assurance that an operator performing setup in commercial manufacturing previously performed a successful setup in a media fill.

E. 与产品直接接触设备的灭菌工艺验证不充分 / Sterilization of product-contact equipment not adequately validated

用于与产品直接接触的设备的灭菌工艺未得到充分验证。例如：

E. The sterilization processes used for equipment that comes into direct contact with your products have not been adequately validated. For example,

1. 验证过程中没有描述生物指示剂（BI）放置位置的具体细节，也无法保证在 xxx 装载模式验证期间对最难到达的位置进行了监测。例如，无菌灌装期间仅在 xxx 软管末端放置一个 BI。软管的长度未作规定。这些软管可被重新清洁并 xxx 至 xxx 次，用于 xxx。未进行风险评估以确定当前 BI 的放置位置是否合理。

1. There are no specific details describing the placement of BIs during validation or assurance that the hardest to reach locations are monitored during xxx load pattern validations. For example, a BI is only placed at the end of thexxx hoses used during aseptic filling. The length of the hoses is not specified. These hoses can be recleaned and xxx up toxxx for xxx A risk assessment wasn’t performed to determine the current BI locations.

2. 你方在 xxx 之前对 xxx 胶塞进行批量灭菌。无法保证在 xxx 过程中将已灭菌胶塞输送至 xxx 区域的 xxx 装置得到灭菌。

2. The firm sterilizesxxx stoppers in bulk, prior toxxx There is no assurance that thexxx delivering sterilized stoppers to the xxx area is sterilized during thexxx process.

3. 装载模式程序所含细节不足，无法确保可重复性。例如，没有说明 xxx 期间工具在 xxx 中的存放方式。

3. Load patterns procedures do not contain enough detail to ensure reproducibility. For example, there is no description of how tools are stored in the xxx during xxx

观察项 2 / Observation 2

你方未能对某批产品或其任何组分无法解释的偏差或不符合质量标准的情况进行彻底调查，无论该批产品是否已经放行销售。

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications whether or not the batch has already been distributed.

A. 注射剂生产线的 B 级区革兰氏阴性菌反复检出未调查 / Reoccurring gram-negative recoveries not investigated

注射剂生产线周围 B 级区反复出现的革兰氏阴性菌检出事件，未开展调查以确定其来源。2025 年报告了以下革兰氏阴性菌检出情况：

A. Reoccurring gram-negative recoveries in the grade B area surrounding the injectable manufacturing lines do not get investigated to determine the source. In 2025, the following gram-negative occurrences were reported:

年份 | 车间 | 检出次数 | 微生物名称

Year | Workshop | Occurrences | Microbial name

xxx

B. 对 xxx 读数的调查不充分 / Inadequate investigation into the xxx reading

2026年4月20日，在观察 xxx 产品、批号 xxx 的 xxx 注射液（USP 规格）灌装过程中，我在约 12:40 观察到控制 xxx RABS 的 xxx 处于 xxx 状态，并拍摄了 xxx 的照片。1:00 后我询问了 xxx 的状态。你方启动调查，确认与 xxx 相连的 xxx RABS 中的管路存在裂纹。调查声称 xxx 的读数在 1:24 时处于允许范围内（合格范围为 xxx）。当我说明在 12:40 观察到 xxx 处于 xxx 状态时，管理层表示这可能由波动引起。调查未评估 xxx 在管路出现裂纹的情况下是否会发生波动；该调查也未解释 1:24 时可接受读数与此前观察结果之间的差异。

B. Inadequate investigation into the xxx reading. While observing filling of batch xxx of xxx Injection, USP, on 20Apr2026, I observed the xxx governing the xxx RABS to be xxx at approximately 12:40pm, and took a photo of the xxx I inquired about the status of the xxx after 1:00pm. The firm initiated an investigation which determined the tube was cracked in the xxx RABS which is connected to the xxx The investigation stated the reading of the xxx was within tolerance at 1:24pm (qualified range xxx When I stated I observed the xxx to be xxx at 12:40pm, management stated this could be due to fluctuation. There was no evaluation as to whether a xxx would fluctuate with a cracked tube. The investigation did not address the discrepancy in the acceptable reading at 1:24pm.

C. 投诉调查缺乏深度和严谨性 / Complaint investigations lack depth and rigor

你方的投诉调查缺乏足够的深度和严谨性，具体缺陷如下：

C. Your firm’s complaint investigations lack adequate depth and rigor as noted in the following deficiencies:

1. 调查未全面评估生产过程中可能导致投诉或缺陷的所有可能因素。例如，涉及 xxx 注射液（USP 规格）瓶盖松动、西林瓶泄漏的投诉 CP2500013，未调查轧盖速度的影响。

1. Investigations do not include a thorough evaluation of all possible factors in the manufacturing process that could have contributed to the complaint or defect. For example, complaint CP2500013, involving xxx Injection USP, for loose caps, and leaking vials, failed to investigate capping speed.

2. 在适用情况下，调查未包括对留样样品的检查和检验，以确定该投诉是否反映更广泛的质量问题。例如，以下投诉的调查期间均未检查留样：涉及 xxx 注射液的 CP2500039、涉及 xxx 注射液的 CP250035、涉及 xxx 注射液的 CP250001，以及涉及 xxx 注射液（USP 规格）的 CP2500030。

2. Investigations fail to include examination and testing of retain samples when applicable to determine if the complaint represents a broader quality issue. For example, retain samples were not inspected during the investigations of the following complaints, CP2500039 involving xxx Injection, CP250035 involving xxx Injection, CP250001 involving xxx Injection, and CP2500030 involving xxx Injection, USP.

3. 质量部门不开展设备和工艺审核，而是依赖生产部门自行审核。日志和原始数据始终未得到审核，以识别潜在工艺偏差或设备故障。质量部门将生产设备和日志的审核工作推给生产部门，并在投诉 CP2500039（涉及 xxx 注射液）、CP250035（涉及 xxx 注射液）和 CP250001（涉及 xxx 注射液）的调查中未审核原始数据。

3. Quality does not perform an equipment and process review, but instead relies on Production to conduct their own review. Logs and raw data are consistently not reviewed to identify potential process deviations or equipment malfunctions. Quality defers production equipment and log review to the production department, and did not review raw data in complaint investigations CP2500039 involving xxx Injection, CP250035 involving xxx Injection, and CP250001 involving xxx Injection.

4. 在投诉 CPC240024 的调查中，你方未对类似可能性进行回顾性审查。该投诉涉及 xxx 注射液（USP 规格）的 xxx 包装设计（artwork）错误，包含不正确的 xxx 使用说明。此外，CAPA 未充分针对根本原因。

4. Your firm did not perform a retrospective review for similar possibilities during the investigation of complaint CPC240024, involving a xxx packaging artwork error of xxx Injection, USP, with the incorrect xxx instructions. Additionally, the CAPA did not adequately address the root cause.

观察项 3 / Observation 3

未建立旨在防止声称无菌的药品发生微生物污染的程序（验证存在缺失）。

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established.

A. 无菌操作技术不良 / Inadequate aseptic technique

2026年4月20日，通过视频回顾和现场观察 xxx 车间 xxx 注射液的"无菌灌装"过程，发现无菌操作技术不良。不一致之处包括：

A. Inadequate aseptic technique was observed in the review of videos and while watching the aseptic filling of xxx Injection in workshop xxx on 20Apr2026. Discrepancies include:

1. 操作人员在添加胶塞时阻挡了首层气流。该情况出现在 xxx 车间、xxx 无菌灌装线。

2. 观察到一名操作人员需将上半身探入 RABS 单元内取回和归还镊子（xxx 车间）。

3. 执行干预操作时手臂越过 xxx 西林瓶上方，受影响的西林瓶未被移走。

1. Operators block first air during the addition of stoppers. This was seen in workshops xxx xxx aseptic filling lines.

2. An operator was seen having to lean his upper body inside the RABS unit to retrieve and return forceps in workshop xxx

3. Reaching over xxx vials during the execution of an intervention. The affected vials were not removed.

B. 目检人员资质确认程序不充分 / Inadequate visual inspection qualification program

你方的目检资质确认程序不足以证明检查人员能够可靠检出无菌注射剂产品中的所有缺陷类型。

B. The firm’s visual inspection qualification program is inadequate to demonstrate that inspectors can reliably detect all defect types in sterile injectable products.

1. 目检资质确认程序缺乏质量部门（Quality Unit）的充分监督和控制。生产人员保管资质确认套件、实施资质确认测试并作出合格/不合格判定，质量部门仅审核瓶子的状态。这种安排既无法确保按照书面程序正确实施资质确认测试，也无法确保对检查人员绩效进行客观评价。

1. Your visual inspection qualification program lacks adequate Quality Unit over-site and control. Production personnel maintain qualification kits, administer qualification tests, make pass/fail determination with only a Quality review of the bottle condition. This arrangement fails to ensure the proper administration of qualification tests according to a written procedure as well as fails to ensure objective evaluation of inspector performance.

2. 你方 xxx nL 液体目检资质确认套件缺少对资质确认瓶中实际粒子尺寸的书面验证记录。例如，xxx 号瓶标签标注含有 xxx μm 的 xxx 粒子，但目视观察表明该粒子明显更大。你方未提供显微镜测量结果或任何客观证据来证实任一资质确认瓶中粒子的实际尺寸。在未知实际粒子尺寸的情况下，无法恰当评估检查人员在规定粒径限度下检测粒子的能力。

2. Your firm’s xxx nL liquid visual inspection qualification kit lacks documented verification of the actual particle sizes present in the qualification vials. For example, vial xxx is labeled as containing a xxx particle of xxx um, but visual observation indicated the particle is significantly larger. Your firm has not provided microscopic measurements, or objective evidence confirming the actual size of particles in any qualification vial. Inspectors can not be properly assessed on their ability to detect particles at specified size limits when the actual particle sizes are unknown.

3. 你方 xxx 目检资质确认套件（xxx mL）不充分，因为它未包含生产操作中可能合理出现的具有代表性的外来颗粒物类型和尺寸范围。该套件仅包含用于 xxx 产品的 xxx μm 纤维，无法检验检查人员检出其他常见缺陷（如不同尺寸和颜色的玻璃颗粒或纤维）的能力。

3. Your firm’s xxx visual inspection qualification kit, xxx mL, is inadequate because it does not include representative range of foreign particulate matter types and sizes that could reasonably occur during manufacturing operations. The kit only contains xxx um fiber for xxx products, which fails to challenge the inspector’s ability to detect other common defects, such as glass particles, or fibers, of varying sizes and colors.

4. xxx nL 液体目检资质确认套件不含浑浊样品、白点/白色颗粒或有色颗粒。

4. The xxx nL liquid visual inspection qualification kit does not contain turbid samples, white spots/particles, or colored particles.

5. 你方 xxx 目检资质确认程序仅使用 xxx nL 西林瓶对检查人员进行资质确认，而商业化生产涵盖的瓶型尺寸范围为 xxx nL 至 xxx nL。这种单一尺寸的做法无法充分确保检查人员具备在生产所用容器尺寸和灌装体积范围内检出缺陷的能力，因为检出难度随容器几何形状、灌装体积和观察角度而变化。

5. Your xxx visual inspection qualification program uses only xxx nL vials for inspector qualification, while your commercial production includes vial sizes ranging from xxx nL to xxx nL. This single-size approach fails to adequately qualify inspectors to detect defects across the range of container sizes and fill volumes used in production, as detection difficulty varies with container geometry, fill volume, and viewing angles.

6. 展现颗粒物质的投诉照片未被纳入培训或资质确认套件，致使检查人员无法学习识别实际生产中的真实缺陷。

6. Complaint photos depicting particulate matter are not incorporated into training or qualification kits, preventing inspectors from learning to recognize real world defects

7. 在实验室（放行检验）目检人员资质确认之前，制作了一套含 xxx 个项目的资质确认套件。该套件中的 xxx 个外来异物缺陷件是从其他缺陷套件中随机挑选的，导致该资质确认套件中装有不同尺寸液体瓶 xxx xxx。该套件不能反映放行检验时实验室实际检验产品的方式。其他缺陷包括：

7. Axxx item qualification kit is made prior to qualify personnel performing visual inspection in the laboratory (release testing). The xxx foreign object defects in this kit are randomly selected from other defect kits, resulting in a qualification kit containing liquid vials of different sizes xxx xxx This kit is not reflective of how product is tested in the laboratory during release. Additional deficiencies include:

• 资质确认套件始终含有 xxx 个缺陷件。

• 分析人员在记录被检瓶状态后，揭下标签露出原始瓶号，并在表格上记录该编号。所有合格瓶均以 xxx 前缀标识。

• 监考人员确认缺陷件识别正确与否的过程未形成文件记录。

• The qualification kit always contains xxx defects.

• After documenting the status of the container being inspected, the analyst peels off the sticker revealing the original vial number and documents that number on the form. All good vials are identified with a prefix of xxx

• When the proctor confirms the correct identification of the defect is not documented.

C. 干预未按位置/类型进行趋势分析 / Interventions not trended

干预未根据发生位置或属于 xxx 干预还是 xxx 干预进行趋势分析。这影响了培养基模拟灌装的准确性，并可能导致并非所有操作都反映在烟雾试验中。

C. Interventions are not trended based on the location of where the intervention takes place, or whether the intervention was xxx or a xxx intervention. This affects the accuracy of the media fills and results in all activities potentially not being reflected in the smoke studies.

D. 无菌灌装期间使用的 xxx 文件记录不充分 / Inadequate documentation for xxx

你方未能建立并维护无菌灌装操作期间安装于 xxx 的 xxx 的充分文件记录。例如：

D. Your firm failed to establish and maintain adequate documentation for xxx installed in the xxx during aseptic filling operations. For example:

• 你方未记录也未跟踪 xxx 的制造商序列号或批号。

• 你方尚未建立 xxx 寿命管理（lifecycle）程序，用以跟踪 xxx 制造商的有效期。

• You do not record nor track manufacturer serial numbers or lot numbers on the xxx

• You have not established a xxx lifecycle program where you track xxx manufacture’s expiration dates

观察项 4 / Observation 4

无菌生产区域的环境条件监测系统存在缺陷。具体而言，在审核环境监测程序时发现以下不一致之处：

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specifically, the following discrepancies were noted during review of the environmental monitoring program:

A. 灌装结束时未对所有 xxx 取样 / Not all xxx sampled at end of batch

并非所有在注射剂无菌灌装期间使用的 xxx 都在批次结束时取样。xxx 车间环境控制风险评估 C-VP-206-71000-2617 规定，在批生产后对 xxx 进行取样监测。这导致 xxx 的监测为 xxx。该评估并非基于对 xxx 干预发生位置的评估。类似的风险评估导致 xxx 在 xxx 中 xxx，而无论这些 xxx 是否在无菌灌装期间被使用。

A. Not all xxx used during aseptic filling of injectable products are sampled at the end of the batch. C-VP-206-71000-2617 Risk Assessment of Environmental Control in Workshop xxx specifies sampling of xxx to monitor after batch manufacturing. This results in xxx being monitored xxx This assessment was not based on an evaluation of xxx where interventions take place. Similar risk assessments resulted in xxx in xxx regardless of whether they were used during aseptic filling.

B. 胶塞添加区域无环境监测 / No environmental monitoring at stopper addition

由于空间限制，在 xxx 胶塞添加区域未开展环境监测（非活性粒子、浮游菌、沉降碟）。仅在 xxx 层流罩 xxx 区域（操作人员将 xxx 胶塞袋传递至胶塞斗的区域）执行粒子计数。监测期间该区域未进行任何操作。

B. Due to space constraints, no environmental monitoring (non-viable particles, viable air, settle plates) is performed where xxx stopper addition takes place. Only particle counting is executed in the xxx hood xxx area where operator passes xxx stopper bags to stopper bowl areas). No activities are performed in this area during monitoring.

观察项 5 / Observation 5

你方未能建立充分的清洁和消毒制度，以对房间和设备进行清洁消毒从而产生无菌条件。

Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

2026年4月20日，在 xxx 车间完成 xxx 注射液（USP 规格）生产后进行清洁时，发现以下不一致之处：

Discrepancies were noted during the cleaning performed on 20Apr2026 in workshop xxx after the manufacture of xxx Injection-USP including:

A–D. 清洁作业违规 / Cleaning practice deficiencies

A. 观察到操作人员在清洁时跪在 xxx 上，并且手臂越过设备、身体倚靠设备进行清洁。

B. 使用同一块抹布清洁多台设备，包括先清洁 xxx RABS 的下部，随后清洁 xxx RABS 的内部 xxx。

C. 只有生产准备期间或取出卡塞胶塞所用的镊子经过了 xxx 处理。其余所有镊子（包括用于取出 xxx 掉落/卡住西林瓶的镊子）均未经过 xxx 处理，这些镊子一直留在无菌灌装线上。这些镊子未记录为在 xxx 循环期间存在于现场。这解释了 xxx 车间 xxx 线 A 级区内处于 xxx 状态的镊子数量。

D. 没有数据支持在 xxx 前用 xxx 喷洒 xxx RABS xxx 可对 xxx 的整个表面进行消毒。对培养基模拟灌装视频的回顾显示，操作人员仅用最少 xxx 次喷溅来消毒 RABS xxx。

A. Operators were seen kneeling on the xxx as well as reaching over and leaning on equipment during cleaning.

B. Using the same cloth to clean numerous pieces of equipment, including cleaning the lower parts of the xxx RABS followed by cleaning the inside of xxx RABS xxx

C. Only the forceps used during setup or the removal of a stuck stopper are xxx All remaining forceps, including those used in the removal of xxx fallen/jammed vials are not xxx These forceps remain on the aseptic filling lines indefinitely. These forceps are not documented as being present during the xxx cycle. This accounts for xxx forceps inside the grade A area in workshop xxx xxx line.

D. There is no data in support of spraying of the xxx RABS xxx with xxx prior to xxx disinfects the entire surface of the xxx Review of media fill videos showed an operator using as few as xxx squirts to disinfect a RABS xxx

观察项 6 / Observation 6

自动、机械、电子设备的日常校准、检查和检验未按照旨在确保其正常性能的书面程序执行。审核 xxx 车间无菌灌装线的 xxx 重量检查系统时发现以下不一致之处：

Routine calibration, inspection, checking of automatic, mechanical, electronic equipment is not performed according to a written program designed to assure proper performance. The following discrepancies were noted during the review of the xxx weight check systems on aseptic filling lines in workshops xxx

A–C. 重量检查系统缺陷 / Weight check system deficiencies

A. xxx 车间：使用前对 xxx 天平进行的重量检查未覆盖实际称量范围。天平使用一枚 xxx 砝码进行核查，而所称量物品的近似质量为约 xxx 和 xxx（空瓶和满瓶）。整个灌装过程中未执行人工重量检查。该系统用于 xxx 注射剂的无菌灌装。

B. 在开始生产前，未确认系统拒收过量灌装和欠量灌装瓶的能力。功能检查（于 xxx 执行）所用瓶子未经过称量，以确认接近上、下重量限值的瓶子均能被拒收。验证经理确认，低重量瓶由 xxx xxx 制作，且这些瓶子 xxx 至指定的过量灌装瓶处，因此在 xxx 车间和 xxx 车间执行功能检查时，瓶子的过量/欠量灌装状况一目了然。这影响了 xxx 注射液 xxx 及 xxx ng/瓶，以及 xxx 注射液（USP 规格）xxx 的检查。

C. 尽管程序有规定，但用于执行 xxx 车间 xxx 重量检查的 xxx 天平未执行过 xxx 检查。生产过程中未执行人工重量检查。

A. Workshop xxx The weight checks performed on the xxx balances prior to use, do not bracket the amount being weighed. The balances are verified using a xxx weight while the approximate mass of the items being weighed is approximately xxx and xxx (empty and filled vial). No manual weight checks are performed throughout filling. This system is used in the aseptic filling xxx Injection.

B. The ability of the system to reject over filled and under filled vials is not confirmed prior to start of manufacturing. The vials used during the functionality check, performed xxx are not weighed out to confirm rejects near the upper and lower weight limits. The Validation Manager confirmed the low weight vials are made by xxx xxx and that they xxx to the designated overfill vial so the vials are obviously over and under filled during the functionality check performed in workshopsxxx and xxx This affectsxxx Injectionxxx and xxx ng/vial andxxx Injection, USP xxx

C. Although required by procedure, no xxx checks have been performed on the xxx balances used to performxxx weight checks in the xxx workshop. No manual weight checks are performed during manufacturing.

观察项 7 / Observation 7

未建立控制程序来规定中间控制——这些中间控制用于验证可能造成中间物料和药品特性变异的相关生产过程的性能。

Control procedures are not established that describe in process controls which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process materials and the drug product.

A–C. 中间控制方法未经验证 / In-process inspection methods not validated

A. 你方未能验证用于评估无菌灌装 xxx 注射剂 xxx 的中间检查方法。

A. Your firm failed to validate the in-process inspection method to evaluate xxx of aseptically xxx Injection.

xxx

• 目前你方采用 xxx xxx 方法，但未提供文件化证据证明该方法在准确性、精密度或可重复性方面已经过验证。

• 没有形成文件的 xxx 接受标准。

• 没有对执行 xxx 检查的人员形成文件的培训方案，包括没有目检培训教具或能力评估，以确保 xxx 技术的一致性。

• Currently you use xxx xxx but provided no documented evidence that this method has been validated for accuracy, precision, or reproducibility.

• There is no documented acceptance criteria for xxx

• There is no documented training program for personnel performing xxx inspections, including no visual training aids or competency assessments to ensure consistent xxx technique.

B. 用于检验 xxx 干预期间所用 xxx 无菌性的方法——P-QS-MA-900017-A01《xxx 检查操作规程》——未经验证。

C. 使用 OpenLab 2.4 软件生成的色谱图未执行进针（injection）核对（reconciliation）。

B. The method used to test the sterility of xxx used during xxx interventions, P-QS-MA-900017-A01 Operating Procedure for Inspection of xxx has not been validated.

C. Reconciliation of injections is not performed on the chromatograms generated using OpenLab 2.4 software.