FDA对江苏豪森药业连云港无菌车间签发483检查观察报告，列7项观察

2026年4月16日至24日，美国食品药品监督管理局（FDA）对江苏豪森药业集团有限公司（Jiangsu Hansoh Pharmaceutical Group Co. Ltd.，FEI 3008316144，地址：连云港经济技术开发区东晋路5号，邮编222069）的无菌药品生产设施进行检查，签发 FDA 483 检查观察报告（Form FDA 483），列出 7 项观察，涉及气流可视化（烟雾）研究、培养基模拟灌装、去污染验证、投诉调查、目视检查资质确认、环境监测、清洁消毒与设备校准等。如下：

DEPARTMENT OF HEALTH AND HUMAN SERVICES

美国卫生与公众服务部

FOOD AND DRUG ADMINISTRATION

美国食品药品监督管理局（FDA）

DATE(S) OF INSPECTION：4/16/2026 – 4/24/2026

检查日期：2026年4月16日 – 2026年4月24日

FEI NUMBER：3008316144

FEI 编号（企业识别号）：3008316144

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED：Fred Lu, Head of Products Division (Vice President)

报告交付对象姓名及职务：Fred Lu，产品部门负责人（副总裁）

FIRM NAME：Jiangsu Hansoh Pharmaceutical Group Co. Ltd.

公司名称：江苏豪森药业集团有限公司

STREET ADDRESS：No. 5 Dongjin Road, Economic and Technical Development Zone

街道地址：经济技术开发区东晋路5号

CITY, STATE, ZIP CODE, COUNTRY：Lianyungang, Jiangsu 222069

城市、州、邮政编码、国家：江苏省连云港市，邮编222069

TYPE ESTABLISHMENT INSPECTED：Sterile drug manufacturer

被检查机构类型：无菌药品生产商

This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.

本文件列出 FDA 代表在检查贵方设施期间提出的观察项。这些属于检查性观察，不代表 FDA 对贵方合规性的最终判定。如贵方对某项观察有异议，或已实施、计划实施针对某项观察的纠正措施，可在检查期间与 FDA 代表讨论该异议或措施，或将相关信息提交至上文地址的 FDA。如有任何疑问，请通过上文电话号码和地址联系 FDA。

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

在检查贵方工厂期间，我方观察到以下事项：

Observation 1

观察项 1

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

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

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 (b)(4) as well as the (b)(4) line, the following discrepancies were noted:

A. 无法提供科学证据证明贵公司气流可视化研究中所用烟雾的来源是中性浮力的。在审查贵公司（b)(4)车间以及（b)(4)生产线的无菌灌装线烟雾研究视频期间，注意到以下不符之处：

1. The positioning of the (b)(4) ducts of the (b)(4) 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 (b)(4)

1. （b)(4) RABS 的（b)(4)风管相对于B级区的布置位置，可能使B级区气流发生短路，导致洁净室内空气向上流动。该区域未进行烟雾研究，以证明（b)(4)车间无菌灌装线具有足够的气流。

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.

2. 录制气流视频时烟雾直接朝上，未能提供均匀的烟雾幕帘，以便评估气流。

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

3. 在多份烟雾研究视频中注意到存在湍流，但公司在审核和批准期间未对其进行评估或处理。

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.

4. 在发生操作活动的位置没有烟雾。此外，还注意到烟雾快速消散，这降低了检测涡流和不良气流的能力。

5. When the RABS (b)(4) is (b)(4), first air does not reach the product contact surfaces.

5. 当 RABS（b)(4)处于（b)(4)状态时，首过空气无法到达产品接触表面。

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 (b)(4) ml vial in workshop (b)(4) requires a (b)(4) simulation of maintenance in the filling line. On 17Oct2025, the maintenance personnel performed an activity inside the RABS for approximately (b)(4) then remained standing (b)(4) the RABS with the (b)(4) for the remaining (b)(4). The operator did not perform any additional activities during this time and was considered qualified by this media fill.

B. 培养基模拟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，而未模拟实际的操作活动。例如，C-VP-206-026000-2541《（b)(4)车间（b)(4) ml西林瓶培养基模拟灌装验证方案》要求在灌装线中对维护操作进行（b)(4)的模拟。2025年10月17日，维护人员在RABS内执行了约（b)(4)的操作，随后在剩余（b)(4)时间内手持（b)(4)站在RABS（b)(4)。该操作员在此期间未执行任何额外操作，却因此次模拟灌装被认定为合格。

C. Your firm's (b)(4) decontamination validation for aseptic processing areas has not been adequately validated to demonstrate effective sterilization of all critical surfaces.

C. 贵公司对无菌加工区域的（b)(4)去污染验证未得到充分验证，无法证明对所有关键表面实现了有效灭菌。

1. Deficient (b)(4) design

1. （b)(4)设计存在缺陷

• Workshop (b)(4) were observed, (b)(4) (b)(4). Thus creating areas of occlusion not fully exposed to (b)(4).

• 观察到（b)(4)车间，（b)(4)（b)(4)。由此形成了未完全暴露于（b)(4)的遮蔽区域。

• Workshops (b)(4) do not (b)(4) (b)(4) observed were not (b)(4). Additionally, (b)(4) were not (b)(4) during (b)(4) process.

• （b)(4)车间未（b)(4)，观察到的（b)(4)未（b)(4)。此外，在（b)(4)过程中（b)(4)未被（b)(4)。

• You have not evaluated the (b)(4) efficacy in (b)(4) areas of the (b)(4)

• 贵公司未评估（b)(4)的（b)(4)区域中（b)(4)的有效性。

2. Inadequate (b)(4) sterilization assurance

2. （b)(4)灭菌保证不足

- (b)(4) are redacted, prior to initial installation (b)(4)

- 在初始安装（b)(4)之前，（b)(4)被涂黑遮盖。

- There is no assurance that (b)(4) are completely and uniformly covered by the (b)(4) during routine decontamination cycles

- 无法保证在常规去污染周期中（b)(4)被（b)(4)完全且均匀地覆盖。

3. Incomplete validation documentation

3. 验证文件不完整

- There is no list of equipment that remains in the room during (b)(4) cycle, in the validation protocol or in the report

- 验证方案或报告中，没有在（b)(4)周期期间保留在房间内的设备清单。

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

- 验证方案和报告中，没有关于生物指示剂（BI）和化学指示剂放置具体位置的记录。

- US marketed products manufactured in Workshop (b)(4) include (b)(4)

- 在（b)(4)车间生产的销往美国市场的产品包括（b)(4)（此段内容被大面积涂黑）。

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, (b)(4) 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 versus 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.

D. 未定义在培养基模拟灌装中应执行的固有干预或纠正性干预，以认定操作员具备无菌灌装操作资格。例如，（b)(4)名操作员被记录为在商业化生产中执行装机。其中一名操作员执行设备的装机，包括无菌连接，其余操作员通过向主操作员传递设备来协助。批记录中未区分主操作员与辅助操作员。培养基模拟灌装也以同样方式处理，无法确定谁是辅助操作员、谁执行了无菌连接。这导致无法保证在商业化生产中执行装机的操作员此前已在模拟灌装中成功执行过装机。

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

E. 用于与产品直接接触设备的灭菌工艺未得到充分验证。例如：

1. There are no specific details describing the placement of BIs during validation or assurance that the hardest to reach locations are monitored during (b)(4) load pattern validations. For example, a BI is only placed at the end of the (b)(4) hoses used during aseptic filling. The length of the hoses is not specified. These hoses can be recleaned and (b)(4) up to (b)(4) for (b)(4) A risk assessment wasn't performed to determine the current BI locations.

1. 没有具体细节描述验证期间生物指示剂（BI）的放置位置，也无法保证在（b)(4)装载模式验证中监测到最难到达的位置。例如，生物指示剂仅放置在无菌灌装所用（b)(4)软管的末端。软管的长度未作规定。这些软管可被重新清洗并（b)(4)，最多（b)(4)用于（b)(4)。未进行风险评估来确定当前的生物指示剂位置。

2. The firm sterilizes (b)(4) stoppers in bulk, prior to (b)(4) There is no assurance that the (b)(4) delivering sterilized stoppers to the (b)(4) area is sterilized during the (b)(4) process.

2. 公司在（b)(4)之前对（b)(4)胶塞进行散装灭菌。无法保证将已灭菌胶塞输送至（b)(4)区域的（b)(4)在（b)(4)过程中是无菌的。

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 (b)(4) during (b)(4)

3. 装载模式程序所含细节不足，无法保证可重现性。例如，未描述工具在（b)(4)期间如何存放于（b)(4)中。

Observation 2

观察项 2

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.

贵公司未能彻底调查批次或其任何组分不符合其任何质量标准（无论该批次是否已放行销售）的任何无法解释的偏差或不合格。

A. Reoccuring 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:

A. 注射剂生产线周围B级区反复出现的革兰氏阴性菌回收结果，未得到调查以确定其来源。2025年报告了以下革兰氏阴性菌事件：

（Table: Year | Workshop | Occurrences | Microbial name — 表格内容已被涂黑遮盖）

（表格：年份 | 车间 | 次数 | 微生物名称 — 表格内容已被涂黑遮盖）

B. Inadequate investigation into the (b)(4) reading. While observing filling of batch (b)(4) of (b)(4) Injection, USP, on 20Apr2026, I observed the (b)(4) governing the (b)(4) RABS to be (b)(4) at approximately 12:40pm, and took a photo of the (b)(4) I inquired about the status of the (b)(4) after 1:00pm. The firm initiated an investigation which determined the tube was cracked in the (b)(4) RABS which is connected to the (b)(4) The investigation stated the reading of the (b)(4) was within tolerance at 1:24pm (qualified range (b)(4) When I stated I observed the (b)(4) to be (b)(4) at 12:40pm, management stated this could be due to fluctuation. There was no evaluation as to whether a (b)(4) would fluctuate with a cracked tube. The investigation did not address the discrepancy in the acceptable reading at 1:24pm.

B. 对（b)(4)读数的调查不充分。2026年4月20日，在观察（b)(4) 注射剂, USP 的（b)(4)批次灌装时，我观察到控制（b)(4) RABS 的（b)(4)在约下午12:40处于（b)(4)状态，并拍摄了该（b)(4)的照片。下午1:00之后，我询问了该（b)(4)的状态。公司启动调查，确定与（b)(4)相连的（b)(4) RABS 中的管子出现破裂。调查称（b)(4)的读数在下午1:24处于容差范围内（合格范围为（b)(4)）。当我表示我在下午12:40观察到（b)(4)为（b)(4)时，管理层称这可能是由于波动所致。未评估（b)(4)在管子破裂的情况下是否会发生波动。调查未处理下午1:24读数合格这一矛盾。

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

C. 贵公司的投诉调查缺乏足够的深度和严谨性，存在以下缺陷：

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 (b)(4) Injection USP, for loose caps, and leaking vials, failed to investigate capping speed.

1. 调查未对制造过程中可能导致该投诉或缺陷的所有可能因素进行全面评估。例如，投诉 CP2500013（涉及（b)(4) 注射剂 USP，盖子松动、药瓶泄漏）未调查压盖速度。

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 (b)(4) Injection, CP250035 involving (b)(4) Injection, CP250001 involving (b)(4) Injection, and CP2500030 involving (b)(4) Injection, USP.

2. 调查未在适用时包括对留样的检查和检测，以确定该投诉是否代表更广泛的质量问题。例如，在以下投诉的调查中未检查留样：CP2500039（涉及（b)(4) 注射剂）、CP250035（涉及（b)(4) 注射剂）、CP250001（涉及（b)(4) 注射剂）以及 CP2500030（涉及（b)(4) 注射剂, USP）。

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 CP250039 involving (b)(4) Injection, CP250035 involving (b)(4) Injection, and CP250001 involving (b)(4) Injection.

3. 质量部门未进行设备和工艺审查，而是依赖生产部门自行审查。日志和原始数据始终未得到审查，以识别潜在的工艺偏差或设备故障。质量部门将生产设备和日志的审查交由生产部门负责，且在投诉调查 CP250039（涉及（b)(4) 注射剂）、CP250035（涉及（b)(4) 注射剂）和 CP250001（涉及（b)(4) 注射剂）中未审查原始数据。

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

4. 贵公司在调查投诉 CPC240024（涉及（b)(4) 注射剂, USP 的（b)(4)包装图稿错误，带有错误的（b)(4)说明）期间，未对类似可能性进行回顾性审查。此外，纠正与预防措施（CAPA）未充分处理根本原因。

Observation 3

观察项 3

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

未建立旨在防止声称无菌的药品受到微生物污染的程序。

A. Inadequate aseptic technique was observed in the review of videos and while watching the aseptic filling of (b)(4) Injection in workshop (b)(4) on 20Apr2026. Discrepancies include:

A. 在审查视频时，以及2026年4月20日观察（b)(4)车间（b)(4) 注射剂 的无菌灌装时，发现无菌操作不足。不符之处包括：

1. Operators block first air during the addition of stoppers. This was seen in workshops (b)(4) (b)(4) aseptic filling lines.

1. 操作员在添加胶塞时阻挡首过空气。在（b)(4)（b)(4)车间的无菌灌装线观察到这一情况。

2. An operator was seen having to lean his upper body inside the RABS unit to retrieve and return forceps in workshop (b)(4)

2. 观察到一名操作员在（b)(4)车间不得不将上半身探入 RABS 单元内，以取回和放回镊子。

3. Reaching over (b)(4) vials during the execution of an intervention. The affected vials were not removed.

3. 在执行干预时越过（b)(4)个西林瓶上方。受影响的西林瓶未被移除。

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

B. 公司的目视检查资质确认程序，不足以证明检查人员能够可靠地检出无菌注射产品中的所有缺陷类型。

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.

1. 贵公司的目视检查资质确认计划缺乏质量部门充分的监督和控制。生产人员维护资质确认测试套装、实施资质确认测试、做出通过/不通过判定，质量部门仅审查瓶体状况。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表现进行客观评价。

2. Your firm's (b)(4) mL liquid visual inspection qualification kit lacks documented verification of the actual particle sizes present in the qualification vials. For example, vial (b)(4) is labeled as containing a (b)(4) particle of (b)(4) 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.

2. 贵公司的（b)(4) mL 液体目视检查资质确认套装，缺乏对资质确认瓶中所含实际颗粒尺寸的书面验证。例如，（b)(4)号瓶被标注为含有（b)(4) um 的（b)(4)颗粒，但目视观察显示该颗粒明显更大。贵公司未提供显微测量结果或客观证据，来确认任何资质确认瓶中颗粒的实际尺寸。当实际颗粒尺寸未知时，无法正确评估检查人员在规定尺寸限度下检出颗粒的能力。

3. Your firm's (b)(4) visual inspection qualification kit, (b)(4) 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 (b)(4) um fiber for (b)(4) 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.

3. 贵公司的（b)(4) mL 目视检查资质确认套装是不充分的，因为其未包含制造操作中可能合理出现的各类异物颗粒的代表性类型和尺寸。该套装仅含有用于（b)(4)产品的（b)(4) um 纤维，无法挑战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。

4. The (b)(4) mL liquid visual inspection qualification kit does not contain turbid samples, white spots particles, or colored particles.

4. （b)(4) mL 液体目视检查资质确认套装不含混浊样品、白点颗粒或彩色颗粒。

5. Your (b)(4) visual inspection qualification program uses only (b)(4) mL vials for inspector qualification, while your commercial production includes vial sizes ranging from (b)(4) mL to (b)(4) mL. 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.

5. 贵公司的（b)(4)目视检查资质确认程序仅使用（b)(4) mL 的西林瓶进行检查人员资质确认，而贵公司的商业化生产涵盖从（b)(4) mL 至（b)(4) mL 的多种西林瓶规格。这种单一规格的做法，无法充分认证检查人员在生产所用容器规格和灌装量范围内检出缺陷的能力，因为检测难度随容器几何形状、灌装量和观察角度而变化。

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

6. 描述颗粒物的投诉照片未纳入培训或资质确认套装，使检查人员无法学习识别真实世界中的缺陷。

7. A (b)(4) item qualification kit is made prior to qualify personnel performing visual inspection in the laboratory (release testing). The (b)(4) foreign object defects in this kit are randomly selected from other defect kits, resulting in a qualification kit containing liquid vials of different sizes (b)(4) (b)(4). This kit is not reflective of how product is tested in the laboratory during release. Additional deficiencies include:

7. （b)(4)目检资质确认套装，是在对实验室（放行检测）中执行目视检查的人员进行资质确认之前制作的。该套装中的（b)(4)异物缺陷是从其他缺陷套装中随机选取的，导致资质确认套装包含不同规格的液体瓶（b)(4)（b)(4)。该套装不能反映实验室放行时产品的实际检测方式。其他缺陷包括：

- The qualification kit always contains (b)(4) defects.

- 资质确认套装始终含有（b)(4)缺陷。

- 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 (b)(4)

- 在记录被检容器状态后，分析员撕下贴纸，露出原始瓶号，并将该编号记录在表格上。所有合格瓶均以（b)(4)前缀标识。

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

- 当监考员确认缺陷被正确识别时，未作记录。

C. Interventions are not trended based on the location of where the intervention takes place, or whether the intervention was a (b)(4) or a (b)(4) intervention. This affects the accuracy of the media fills and results in all activities potentially not being reflected in the smoke studies.

C. 干预未按干预发生的位置、或干预是（b)(4)干预还是（b)(4)干预进行趋势分析。这影响了培养基模拟灌装的准确性，并导致所有操作活动可能未在烟雾研究中得到反映。

D. Your firm failed to establish and maintain adequate documentation for (b)(4) installed in the (b)(4) during aseptic filling operations. For example:

D. 贵公司未对无菌灌装操作期间安装在（b)(4)中的（b)(4)建立和维护充分的文件记录。例如：

- You do not record nor track manufacturer serial numbers or lot numbers on the (b)(4)

- 贵公司未记录或追踪（b)(4)上的制造商序列号或批号。

- You have not established a (b)(4) lifestyle program where you track (b)(4) manufacture's expiration dates

- 贵公司未建立（b)(4)生命周期计划，以追踪（b)(4)制造商的有效期。

Observation 4

观察项 4

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:

无菌加工区域在环境条件监测系统方面存在缺陷。具体来说，在审查环境监测计划期间注意到以下不符之处：

A. Not all (b)(4) 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 (b)(4) specifies sampling of (b)(4) to monitor after batch manufacturing. This results in (b)(4) being monitorded (b)(4). This assessment was not based on an evaluation of where interventions take place. Similar risk assessments resulted in (b)(4) in (b)(4) regardless of whether they were used during aseptic filling.

A. 并非注射产品无菌灌装中使用的所有（b)(4)都在批次结束时进行取样。C-VP-206-71000-2617《（b)(4)车间环境控制风险评估》规定在批生产后取样监测（b)(4)。这导致（b)(4)被监测（b)(4)。该评估并非基于对干预发生位置的评价。类似的风险评估导致（b)(4)中的（b)(4)，无论其在无菌灌装期间是否被使用。

B. Due to space constraints, no environmental monitoring (non-viable particles, viable air, settle plates) is performed where (b)(4) stopper addition takes place. Only particle counting is executed in the (b)(4) hood (b)(4) area where operator passes (b)(4) stopper bags to stopper bowl areas). No activities are performed in this area during monitoring.

B. 由于空间限制，在（b)(4)胶塞添加发生的位置未进行环境监测（非活性粒子、活性空气、沉降碟）。仅在操作员将（b)(4)胶塞袋传递到胶塞碗区域的（b)(4)罩（b)(4)区域执行粒子计数。监测期间该区域无操作活动。

Observation 5

观察项 5

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

贵公司未能建立充分的房间和设备清洁与消毒系统，以创造无菌条件。

Discrepancies were noted during the cleaning performed on 20Apr2026 in workshop (b)(4) after the manufacture of (b)(4) Injection-USP including:

2026年4月20日，在（b)(4)车间制造（b)(4) 注射剂-USP 之后进行的清洁中，注意到以下不符之处：

A. Operators were seen kneeling on the (b)(4) as well as reaching over and leaning on equipment during cleaning.

A. 观察到操作员在清洁期间跪在（b)(4)上，以及越过并倚靠在设备上。

B. Using the same cloth to clean numerous pieces of equipment, including cleaning the lower parts of the (b)(4) RABS followed by cleaning the inside of (b)(4) RABS (b)(4).

B. 使用同一块布清洁多台设备，包括先清洁（b)(4) RABS 的下部，随后清洁（b)(4) RABS（b)(4)的内部。

C. Only the forceps used during setup or the removal of a stuck stopper are (b)(4). All remaining forceps, including those used in the removal of (b)(4) fallen/jammed vials are not (b)(4). These forceps remain on the aseptic filling lines indefinitely. These forceps are not documented as being present during the (b)(4) cycle. This accounts for (b) forceps inside the grade A area in workshop (b)(4) (b)(6) line. (b)(4)

C. 只有装机期间使用、或用于移除卡住胶塞的镊子被（b)(4)。所有其余镊子，包括用于移除（b)(4)掉落/卡住西林瓶的镊子，均未被（b)(4)。这些镊子无限期地留在无菌灌装线上。这些镊子未被记录为在（b)(4)周期期间存在。这导致（b)(4)车间（b)(6)生产线的 A级区内有（b)把镊子。（b)(4)

D. There is no data in support of spraying of the (b)(4) RABS (b)(4) with (b)(6) prior to (b)(4) disinfects the entire surface of the (b)(4). Review of media fill videos showed an operator using as few as (b)(6) squirts to disinfect a RABS (b)(4)

D. 没有数据支持在（b)(4)之前用（b)(6)对（b)(4) RABS（b)(4)进行喷雾会消毒（b)(4)的整个表面。对培养基模拟灌装视频的审查显示，一名操作员仅用（b)(6)次喷射来消毒 RABS（b)(4)。

Observation 6

观察项 6

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 (b)(4) weight check systems on aseptic filling lines in workshops (b)(4)

未按照旨在确保设备正常性能的书面计划，对自动化、机械、电子设备进行常规校准、检查和核查。在审查（b)(4)车间无菌灌装线上的（b)(4)重量检查系统期间，注意到以下不符之处：

A. Workshop (b)(4) The weight checks performed on the (b)(4) balances prior to use, do not bracket the amount being weighed. The balances are verified using a (b)(6) weight while the approximate mass of the items being weighed is approximately (b)(6) and (b)(6) (empty and filled vial). No manual weight checks are performed throughout filling. This system is used in the aseptic filling (b)(4) Injection.

A. （b)(4)车间：在使用前对（b)(4)天平执行的重量检查，未覆盖被称量物品的重量范围。天平使用（b)(6)砝码进行验证，而被称量物品的近似质量为约（b)(6)和（b)(6)（空瓶和满瓶）。整个灌装过程中未执行手动重量检查。该系统用于（b)(4) 注射剂 的无菌灌装。

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 (b)(4) 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 (b)(6) and that they (b)(4) to the designated overfill vial so the vials are (b)(4) obviously over and under filled during the functionality check performed in workshops (b)(4) and (b)(4) This affects (b)(4) injection (b)(4) and (b)(4)ng/vial and (b)(4) Injection, USP (b)(4)

B. 在开始生产前，未确认系统剔除超灌和欠灌西林瓶的能力。功能性检查（执行（b)(4)）中使用的西林瓶未进行称重，以确认在上下重量限度附近的剔除情况。验证经理确认，低重量瓶通过（b)(6)制造，且它们被（b)(4)到指定的超灌瓶，因此在（b)(4)和（b)(4)车间执行的功能性检查中，这些西林瓶明显超灌和欠灌。这影响（b)(4)注射剂（b)(4)和（b)(4)ng/瓶以及（b)(4) Injection, USP（b)(4)。

C. Although required by procedure, no (b)(4) checks have been performed on the (b)(4) balances used to perform (b)(4) weight checks in the (b)(4) workshop. No manual weight checks are performed during manufacturing.

C. 尽管程序有要求，但未对（b)(4)车间用于执行（b)(4)重量检查的（b)(4)天平执行（b)(4)检查。生产过程中未执行手动重量检查。

Observation 7

观察项 7

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.

未建立控制程序，以描述那些用于验证可能导致中间物料和药品特性波动的制造工艺性能的过程内控制。

A. Your firm failed to validate the in-process inspection method to evaluate (b)(4) of aseptically (b)(4) injection.

A. 贵公司未验证用于评估无菌（b)(4)注射剂的（b)(4)的中控检查方法。

(b)(4) (b)(4)

（b)(4)（b)(4)

- Currently you use (b)(4) (b)(4) (b)(4) but provided no documented evidence that this method has been validated for accuracy, precision, or reproducibility.

- 贵公司目前使用（b)(4)（b)(4)（b)(4)，但未提供书面证据证明该方法已就准确性、精密度或重现性进行验证。

- There is no documented acceptance criteria for (b)(4)

- 没有关于（b)(4)的书面验收标准。

- There is no documented training program for personnel performing (b)(4) inspections, including no visual training aids or competency assessments to ensure consistent (b)(4) technique.

- 没有针对执行（b)(4)检查人员的书面培训计划，包括没有目视培训辅助材料或能力评估，以确保一致的（b)(4)技术。

B. The method used to test the sterility of (b)(4) used during (b)(4) interventions, P-QS-MA-900017-A01 Operating Procedure for Inspection of (b)(4) has not been validated.

B. 用于检测（b)(4)干预期间所用（b)(4)的无菌性的方法 P-QS-MA-900017-A01《（b)(4)检查操作规程》未经验证。

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

C. 未对使用 OpemLab 2.4 软件生成的色谱图进行进样次数对账。

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Sandra A Boyd, Investigator

检查人员：Sandra A Boyd

Karen A Briggs, Investigator

检查人员：Karen A Briggs

4/24/2026

2026年4月24日