FDA公布Tailstorm Health 483缺陷报告，涉无菌灌装动态确认、灭菌柜监测与天平砝码点超差

2026年9月29日，FDA公布一则483缺陷报告。

检查对象：Tailstorm Health, Inc

检查日期：2026年8月17日-8月28日

检查员：Nicholas L Hunt、Ronda R Loyd Jones

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:
在对贵公司开展检查期间，我方发现如下问题：

OBSERVATION 1

Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.
用于防止污染或混淆的独立/划定区域，在药品无菌加工相关操作方面存在缺陷。

Specifically, (b)(4) operational/dynamic certification of the (b)(4) Vial Filling, Stoppering and Sealing Machine, ISO 5 (b)(4) Filling Line, cleanroom suite does not represent routine production operations. For example, ISO 5 Filling Line (b)(4) was not fully assembled or in-operation, and there was one cleanroom technician outside the (b)(4) during dynamic nonviable particulate (NVP) monitoring. We observed up to (b)(4) technicians inside the ISO 7 buffer room for the ISO 5 (b)(4) during filling of Lidocaine 2% Injection, 10 mL vial, batch 2608002. Records reviewed included: Project AZ-MVDT261801C-1, (b)(4) Cleanroom Testing and Certification, dated April 2026; and Project AZ-MVDT251301C-1, Cleanroom Suite Certification, dated October 2025. All sterile drugs are manufactured on ISO 5 Filling Line (b)(4). The personnel, line setup, and production operations inside the ISO 5 (b)(4) are the same for aseptically filled and (b)(4) sterilized drugs. Examples of aseptically filled drugs include Lorazepam Injection USP, 2 mg/mL, lot 2510002; and Lorazepam Injection USP, 2 mg/mL, lot 2511001.
具体如下：(b)(4) 小瓶灌装、压塞、轧盖设备（ISO5级(b)(4)灌装线）洁净区的(b)(4)动态确认，无法反映常规生产操作。例如，开展动态非活性粒子（NVP）监测时，ISO5灌装线(b)(4)未完全组装到位、未处于运行状态，且仅有一名洁净室技术员在(b)(4)外部。在2%盐酸利多卡因注射液，10mL西林瓶，批号2608002灌装期间，我方观察到ISO5(b)(4)对应的ISO7缓冲间内最多有(b)(4)名技术员。审阅记录包括：项目AZ-MVDT261801C-1，(b)(4)洁净室测试与确认报告，2026年4月；项目AZ-MVDT251301C-1，洁净区确认报告，2025年10月。所有无菌药品均在ISO5灌装线(b)(4)生产。ISO5(b)(4)内的人员、生产线布置、生产操作，对于无菌灌装产品和(b)(4)灭菌产品均一致。无菌灌装药品示例包括：USP劳拉西泮注射液，2mg/mL，批号2510002；USP劳拉西泮注射液，2mg/mL，批号2511001。

OBSERVATION 2

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written and followed.
用于防止标示为无菌药品发生微生物污染的规程，未建立、未书面化且未得到遵守。

Specifically,
具体如下：

Autoclave

灭菌柜

Qualification and routine monitoring of the (b)(4) equipment ID #PE001, is deficient.
设备编号PE001的(b)(4)灭菌柜，其确认与日常监测存在缺陷。

A. There is inadequate written justification to place (b)(4) in the (b)(4) of the (b)(4) as the only process verification for routine sterilization loads. The rationale for the location of the (b)(4) within the (b)(4) is inadequate.
A. 将(b)(4)放置于(b)(4)的(b)(4)位置，作为常规灭菌装载的唯一工艺验证手段，书面论证依据不充分。对于(b)(4)在(b)(4)内部放置位置的合理性论证不足。

B. Operators do not use Biological Indicators (BIs) (b)(4) sterilization (b)(4). The approved procedures only require BIs during (b)(4) qualification of (b)(4) loads. The most recent (b)(4) qualification is documented in (b)(4).PQ.0004, Performance Qualification. (b)(4) Report, (b)(4) PE001, report approved 06/19/26.
B. 操作人员未在(b)(4)灭菌(b)(4)环节使用生物指示剂（BI）。批准的规程仅要求在(b)(4)装载的(b)(4)确认阶段使用生物指示剂。最近一次(b)(4)确认记录于(b)(4).PQ.0004，性能确认(b)(4)报告，设备(b)(4) PE001，报告批准日期2026年06月19日。

C. Your procedures only require a (b)(4) air removal test during (b)(4) qualification of the (b)(4). Technicians do not perform (b)(4) tests before any routine (b)(4) cycles. There is inadequate written justification for the frequency of air removal tests.
C. 贵公司规程仅要求在(b)(4)的(b)(4)确认阶段开展(b)(4)排气试验。技术员在每一次常规(b)(4)循环前，均不开展(b)(4)试验。对于排气试验的测试频次，书面论证依据不足。

Technicians use (b)(4) PE001 to (b)(4) sterilize finished drug products and sterilize reusable product-contact parts, (b)(4) tubing, (b)(4), utensils, and other items used during production of all commercial sterile drugs on ISO 5 Filling Line (b)(4). Examples of drugs manufactured with product-contact equipment sterilized in PE001 include: Ketamine 10% USP, 100 mg/mL, 5 mL, SDV, lot 2602003; Lidocaine HCl 1%/Epinephrine Bitartrate 10 mcg/mL Injection USP, 10 mL, SDV, lot 2603001; Albuterol Sulfate 0.5%, 10 mL, lot 2512002; and Bupivacaine Hydrochloride 0.5%/Epinephrine Bitartrate 5 mcg/mL Injection, 10 mL vial, lot 2608001.
技术员使用(b)(4) PE001对成品药品，以及ISO5灌装线(b)(4)上所有商业化无菌药品生产所用的可重复使用产品接触部件、(b)(4)软管、(b)(4)、器具和其他物品进行(b)(4)灭菌。使用PE001灭菌产品接触部件所生产药品示例包括：USP 10%氯胺酮，100mg/mL，5mL单剂量西林瓶，批号2602003；USP 1%盐酸利多卡因/10mcg/mL重酒石酸肾上腺素注射液，10mL单剂量西林瓶，批号2603001；0.5%硫酸沙丁胺醇，10mL，批号2512002；0.5%盐酸布比卡因/5mcg/mL重酒石酸肾上腺素注射液，10mL西林瓶，批号2608001。

Media Fill

培养基模拟灌装

D. Operators do not verify the (b)(4) of prepared (b)(4) culture medium used in aseptic process simulation media fills on ISO 5 Filling Line (b)(4). There is inadequate assurance that the (b)(4) is suitable to validate the aseptic filling process for Lorazepam Injection. We reviewed the batch record for Media Fill, batch CHMF/26/001, completed (b)(4), approved 06/11/26.
D. 操作人员未对ISO5灌装线(b)(4)无菌工艺模拟灌装所用的配制好的(b)(4)培养基的(b)(4)进行确认。无法充分保证该(b)(4)适用于劳拉西泮注射液无菌灌装工艺验证。我方审阅了培养基模拟灌装批记录，批号CHMF/26/001，完成于(b)(4)，批准日期2026年06月11日。

E. Technicians do not use BIs for routine or periodic monitoring of the (b)(4) cycle used for (b)(4) of ISO 5 Filling Line (b)(4) and the ISO 7 buffer room before filling.
E. 在灌装前，技术员未使用生物指示剂对ISO5灌装线(b)(4)及ISO7缓冲间的(b)(4)循环开展常规或周期性监测。

F. The (b)(4) surface remains folded inside the open (b)(4) pouch during the (b)(4) cycle for ISO 5 Filling Line (b)(4) and the ISO 7 buffer room. There are no BIs (b)(4) placed inside the partially open pouches to demonstrate the (b)(4) adequately (b)(4) the (b)(4) that are exposed to the environment during installation of the (b)(4) in (b)(4).
F. 在ISO5灌装线(b)(4)和ISO7缓冲间的(b)(4)循环过程中，(b)(4)表面仍折叠放置于开口的(b)(4)包装袋内。未在半开口包装袋内部放置生物指示剂(b)(4)，无法证明在(b)(4)内安装(b)(4)时，(b)(4)可以充分对暴露于环境的(b)(4)进行(b)(4)。

Personnel Monitoring

人员监测

G. Personnel monitoring specifications for (b)(4) hands, forearms, chest, and forehead are not scientifically justified. Your firm uses the ISO 7 microbial monitoring limits (b)(4) CFU/plate alert and (b)(4) CFU/plate action to evaluate samples from operators that use (b)(4) to perform closed-door interventions in the ISO 5 Filling Line (b)(4). Samples collected from operators after open-door interventions are the only personnel samples held to the ISO 5 microbial limits (b)(4) CFU/plate.
G. (b)(4)手部、前臂、胸部、前额的人员监测标准，缺乏科学依据。贵公司采用ISO7微生物警戒限(b)(4)CFU/平皿与行动限(b)(4)CFU/平皿，评估使用(b)(4)在ISO5灌装线(b)(4)内执行闭门干预操作的操作人员样品。仅对开门干预后采集的操作人员人员样品，采用ISO5微生物限度(b)(4)CFU/平皿进行判定。

OBSERVATION 3

Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use and cleaning and maintenance.
药品生产、加工、包装或存放所用设备设计不合理，不利于预期操作、清洁与维护。

Specifically,
具体如下：

(b)(4) System

(b)(4)系统

A. We observed a leaking diaphragm valve after the final (b)(4) step on the (b)(4) skid used to supply (b)(4) for all sterile injectable drugs that contain (b)(4). Examples of drugs that contain (b)(4) from this system include:
A. 我方观察到，为所有含(b)(4)无菌注射药品供给(b)(4)的(b)(4)橇装系统，在最终(b)(4)工序之后有一处隔膜阀泄漏。使用该系统供给(b)(4)所生产含(b)(4)药品示例包括：

• Ketamine 10% USP, 100 mg/mL, 5 mL, SDV, lot 2602003
USP 10%氯胺酮，100mg/mL，5mL单剂量西林瓶，批号2602003

• Lidocaine HCl 1%/Epinephrine Bitartrate 10 mcg/mL Injection USP, 10 mL, SDV, lot 2603001
USP 1%盐酸利多卡因/10mcg/mL重酒石酸肾上腺素注射液，10mL单剂量西林瓶，批号2603001

• Albuterol Sulfate 0.5%, 10 mL, lot 2512002
0.5%硫酸沙丁胺醇，10mL，批号2512002

• Bupivacaine Hydrochloride 0.5%/Epinephrine Bitartrate 5 mcg/mL Injection, 10 mL vial, lot 2608001
0.5%盐酸布比卡因/5mcg/mL重酒石酸肾上腺素注射液，10mL西林瓶，批号2608001

B. There is an approximately one-foot-long (b)(4) connected to the (b)(4) for the (b)(4) on the (b)(4) System.
B. 在(b)(4)系统上，(b)(4)的(b)(4)连接了一根约1英尺长的(b)(4)。

(b)(4) contains a (b)(4) (b)(4) near the middle that leads to a closed (b)(4) on the (b)(4) from the (b)(4) System.
(b)(4)中部带有一个(b)(4)(b)(4)，通向(b)(4)系统(b)(4)上的一处封闭(b)(4)。

(b)(4) System

(b)(4)系统

We observed numerous deficiencies with the design, use, testing, and maintenance of the ambient temperature, (b)(4) construction (b)(4) System dedicated to supply (b)(4) to the (b)(4) equipment ID #PE001, inside the Line (b)(4) Cleanroom suite. Operators use (b)(4) PE001 to sterilize all reusable product-contact parts and (b)(4) sterilize injectable drugs on ISO 5 Filling Line (b)(4).
我方发现，专门用于向灌装线(b)(4)洁净区内设备编号PE001的(b)(4)供给(b)(4)的常温(b)(4)结构(b)(4)系统，在设计、使用、测试和维护方面存在多项缺陷。操作人员使用(b)(4) PE001对所有可重复使用产品接触部件进行灭菌，并在ISO5灌装线(b)(4)对注射药品进行(b)(4)灭菌。

System flow: (b)(4)
系统流程：(b)(4)

C. The (b)(4) System is not sampled or tested for conformance with any written specifications for chemical, microbiological, or physical attributes.
C. 未对(b)(4)系统取样，未检测其化学、微生物、物理属性是否符合书面质量标准。

D. The (b)(4) after the final (b)(4) step which was the beginning of the distribution line is closed. (b)(4) remains stagnant in the (b)(4) System, ambient temperature (b)(4) distribution line, flexible hose connection to the (b)(4) and (b)(4) tank inside the (b)(4) for more than (b)(4) when there is no production scheduled. There was no written justification for the start-up procedure for the (b)(4) System or (b)(4) PE001.
D. 最终(b)(4)工序之后（即分配管线起点）的(b)(4)处于关闭状态。在无生产计划期间，(b)(4)在(b)(4)系统、常温(b)(4)分配管线、连接至(b)(4)和(b)(4)罐的软管内滞留超过(b)(4)时长。针对(b)(4)系统或(b)(4) PE001的启动程序，无书面论证依据。

E. The (b)(4) System includes numerous sanitary threaded connections, hose clamp connections, and (b)(4). This includes (b)(4) hose clamp connections after the final (b)(4) step.
E. (b)(4)系统包含多处卫生级螺纹连接、喉箍软管连接以及(b)(4)，其中包括最终(b)(4)工序之后的(b)(4)喉箍软管连接。

F. The (b)(4) System is not sanitized periodically and there is no written requirement.
F. (b)(4)系统未定期进行消毒，且无书面规程要求。

G. There was unknown brown residue throughout the inside of the (b)(4) housing for the (b)(4).
G. 在(b)(4)的(b)(4)壳体内部，发现不明褐色残留物。

H. The (b)(4) was closed on the approximately 8-inch section of pipe that supplies approximately 20 feet of pipe for the backup filling supply for the (b)(4) System break tank. The 8-inch section of pipe leading from the main (b)(4) flow line to the closed (b)(4) was functionally a (b)(4). The unused about 20 feet of (b)(4) (b)(4) was a (b)(4).
H. (b)(4)系统缓冲罐备用灌装供给管线约20英尺管路，其前端约8英寸管段上的(b)(4)处于关闭状态。从主(b)(4)输送管线通向该关闭(b)(4)的8英寸管段，在功能上属于盲管(b)(4)；闲置的约20英尺(b)(4)(b)(4)属于盲管(b)(4)。

I. The (b)(4) for the drain line was open. The flexible hose connected to the drain line was inserted approximately six inches down through a hole in the floor drain cover plate. Drain from the (b)(4) system was emptying into the drain and contacting the open drain hose for the (b)(4) System. This potentially allows (b)(4) to (b)(4) into the hose under specific conditions.
I. 排放管线的(b)(4)处于开启状态。连接排放管线的软管穿过地漏盖板孔洞，向下插入约6英寸。(b)(4)系统的排放物流入地漏，并接触(b)(4)系统的开放排放软管。在特定条件下，存在(b)(4)通过软管(b)(4)的潜在风险。

Examples of drugs manufactured with product-contact equipment sterilized in (b)(4) PE001 with (b)(4) from the (b)(4) System include: Ketamine 10% USP, 100 mg/mL, 5 mL, SDV, lot 2602003; Lidocaine HCl 1%/Epinephrine Bitartrate 10 mcg/mL Injection USP, 10 mL, SDV, lot 2603001; Albuterol Sulfate 0.5%, 10 mL, lot 2512002; and Bupivacaine Hydrochloride 0.5%/Epinephrine Bitartrate 5 mcg/mL Injection, 10 mL vial, lot 2608001.
使用(b)(4)系统提供(b)(4)、并在(b)(4) PE001灭菌产品接触部件所生产药品示例包括：USP 10%氯胺酮，100mg/mL，5mL单剂量西林瓶，批号2602003；USP 1%盐酸利多卡因/10mcg/mL重酒石酸肾上腺素注射液，10mL单剂量西林瓶，批号2603001；0.5%硫酸沙丁胺醇，10mL，批号2512002；0.5%盐酸布比卡因/5mcg/mL重酒石酸肾上腺素注射液，10mL西林瓶，批号2608001。

There are inadequate written controls for (b)(4) (b)(4) testing and replacement frequency. Technicians use (b)(4) attached to ISO 5 Filling Line (b)(4) to produce all (b)(4) sterilized and aseptically filled drugs.
针对(b)(4)(b)(4)的测试与更换频次，书面管控要求不足。技术员使用安装在ISO5灌装线(b)(4)上的(b)(4)，生产所有(b)(4)灭菌及无菌灌装药品。

J. There is no validation data to support the (b)(4) submersion test that production operators use to test the (b)(4) of (b)(4) after they remove them from ISO 5 Filling Line (b)(4). Operators wipe the (b)(4) with sporicidal, remove them from the (b)(4) after (b)(4) perform (b)(4) tests, (b)(4) sterilize the individually wrapped (b)(4) and then install them on the (b)(4) before the (b)(4) cycle for each (b)(4) sterilized or aseptically filled batch.
J. 生产操作人员从ISO5灌装线(b)(4)取下(b)(4)后，使用(b)(4)浸没试验检测(b)(4)的(b)(4)，该浸没试验无验证数据支持。操作人员使用杀孢子剂擦拭(b)(4)，在(b)(4)之后将其从(b)(4)取下，开展(b)(4)测试；对独立包装的(b)(4)进行(b)(4)灭菌，之后在每一批(b)(4)灭菌或无菌灌装批次的(b)(4)循环前，将其安装至(b)(4)。

K. There is no validation data to support unlimited (b)(4) sterilization cycles of (b)(4) before replacement. (b)(4) are not individually identified. The number of uses and sterilization cycles are not tracked.
K. 无验证数据支持(b)(4)可在更换前不限次数进行(b)(4)灭菌循环。(b)(4)无单独标识，使用次数与灭菌循环次数未进行追踪。

OBSERVATION 4

Written records are not always made of investigations into unexplained discrepancies.
对于无法解释的偏差，并非均开展调查并形成书面记录。

Specifically,
具体如下：

Particulate Matter

可见异物

A. Production processes, procedures, and equipment do not adequately exclude particulates and other potential contaminants from sterile injectable and oral inhalation drug product vials. I reviewed the two most recent (b)(4) reports for Trending of Visible Particle at Visual Inspection. The trend reports include results from 100% visual inspection and AQL inspection of finished sterile drug vials.
A. 生产工艺、规程与设备，无法充分将可见异物及其他潜在污染物排除在无菌注射药品与口服吸入药品西林瓶之外。我方审阅了最新两份目检可见异物趋势(b)(4)报告。趋势报告包含成品无菌西林瓶100%目检及AQL检验结果。

a. PROT.GSP.0025, Visible Particle Trending August-Dec 2025, approved 02/03/26, documents personnel found visible particulates in multiple vials from all (b)(4) batches manufactured and inspected during the review period. The number of vials rejected for particulate matter ranged from (b)(4) (0.03%) to (b)(4) (0.46%) vials in batches that were released.
a. PROT.GSP.0025《可见异物趋势报告 2025年8月-12月》，批准日期2026年02月03日，记录显示：在审阅周期内，所有(b)(4)个生产并检验批次均有多支西林瓶检出可见异物。放行批次中，因可见异物拒收的西林瓶数量占比范围为(b)(4)（0.03%）至(b)(4)（0.46%）。

b. PROT.GSP.0035, Visible Particle Trending January 2026-June 2026, approved 08/18/26, documents personnel found visible particulates in at least one vial from all (b)(4) batches manufactured and inspected during the review period. The number of vials rejected for particulate matter ranged from (b)(4) (<0.01%) to (b)(4) (0.16%) vials.
b. PROT.GSP.0035《可见异物趋势报告 2026年1月-6月》，批准日期2026年08月18日，记录显示：审阅周期内所有(b)(4)个生产并检验批次，至少有一支西林瓶检出可见异物。因可见异物拒收的西林瓶数量占比范围为(b)(4)（<0.01%）至(b)(4)（0.16%）。

B. There is no written investigation of how extrinsic controlled particulates such as non-shedding cleanroom wipes, cleanroom (b)(4), and goggles material routinely enter vials during filling.
B. 对于非掉屑洁净抹布、洁净室(b)(4)、护目镜材料这类外源性可控异物，在灌装过程中持续进入西林瓶的原因，未开展书面调查。

C. There is inadequate scientific justification for the (b)(4) Reject Acceptance Rate Limit for critical defects per batch.
C. 每一批次关键缺陷(b)(4)拒收合格率限值，缺乏充分科学依据。

Balances

天平

D. Dispensing room Balance PE026 was found out-of-tolerance at the (b)(4) and (b)(4) weights during the 10/08/25 calibration. Balance PE026 was found out-of-tolerance at the (b)(4) weight during the 04/15/25 calibration. There was no investigation documented.
D. 配料间天平PE026，在2025年10月08日校准时，(b)(4)和(b)(4)砝码点超差；2025年04月15日校准时，该天平在(b)(4)砝码点超差。未记录相关调查。

E. Dispensing room Balance PE027 was found out-of-tolerance at the (b)(4) and (b)(4) weights during the 10/08/25 calibration. Balance PE027 was found out-of-tolerance at the (b)(4), and (b)(4) weights during the 04/15/25 calibration. There was no investigation documented.
E. 配料间天平PE027，在2025年10月08日校准时，(b)(4)和(b)(4)砝码点超差；2025年04月15日校准时，该天平在(b)(4)、(b)(4)砝码点超差。未记录相关调查。

Warehousing

仓储

F. The (b)(4) Environmental Monitoring Trend Report for the Raw Material (b)(4) storage area (May 1-31, 2026) documents the temperature readings from sensors (b)(4) and (b)(4) exceeded the High Warning Limit of (b)(4) on multiple occasions throughout the month of May 2026. Maximum temperature readings on both sensors approached or reached the High Alarm Limit of (b)(4) during the same period. Quality management stated they notified the engineering department but did not document the excursion or initiate an investigation. Your firm does not have an SOP that addresses maintaining adequate storage conditions, and temperature controls, for raw materials and finished goods stored in the warehouse with instructions on documenting and investigating high warning or high alarm temperature limits excursions.
F. 《原料(b)(4)储存区域(b)(4)环境监测趋势报告（2026年5月1日-31日）》记录：2026年5月整月期间，传感器(b)(4)与(b)(4)的温度读数多次超出(b)(4)高警戒限。同一时段内两个传感器最高温度读数接近或达到(b)(4)高报警限。质量管理人员称已通知工程部，但未记录该偏差，也未启动调查。贵公司无SOP规范仓库内原料与成品的适宜储存条件、温度管控，以及高警戒限/高报警限温度超标的记录与调查要求。

OBSERVATION 5

Laboratory controls do not include the establishment of scientifically sound and appropriate specifications, standards, sampling plans and test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity.
实验室管控未建立科学合理的质量标准、规范、取样方案与检验规程，无法保证辅料与药品符合鉴别、含量、质量与纯度相关标准。

Specifically,
具体如下：

Growth Media

培养基

A. QC microbiology personnel use Standard Methods (b)(4) (Plate Count (b)(4)) for all (b)(4) bioburden samples. There is inadequate justification to use this high (b)(4) (b)(4) instead of (b)(4) designed to recover microorganisms from low (b)(4) (b)(4) systems. Growth promotion on the manufacturer COA for Plate Count (b)(4) only lists Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. It does not include waterborne pathogenic microorganisms of interest such as B. cepacia or P. aeruginosa that are known to colonize high purity (b)(4) systems.
A. QC微生物人员对所有(b)(4)生物负载样品均采用标准方法(b)(4)（平板计数(b)(4)）。采用该高(b)(4)(b)(4)，而非采用适用于低(b)(4)(b)(4)体系微生物回收的(b)(4)，论证依据不足。平板计数(b)(4)厂家COA中的促生长试验仅列出金黄色葡萄球菌、大肠埃希菌、粪肠球菌，未包含洋葱伯克霍尔德菌、铜绿假单胞菌这类可在高纯度(b)(4)系统定植的水生目标致病菌。

B. The firm accepts Plate Count (b)(4) plates based on manufacturer COA and does not perform growth promotion before use.
B. 公司仅依据厂家COA接收平板计数(b)(4)平板，使用前不开展促生长试验。

Nitrogen

氮气

Your firm uses nitrogen for pre-gassing vials and blanketing drug product solution in all lots of Lidocaine/Epinephrine Injection, Bupivacaine/Epinephrine Injection, and Lorazepam Injection. We observed multiple apparent deficiencies related to nitrogen.
贵公司在所有批次利多卡因/肾上腺素注射液、布比卡因/肾上腺素注射液、劳拉西泮注射液生产中，使用氮气对西林瓶预充气并对药液进行氮封。我方发现氮气相关多项明显缺陷。

C. There was inadequate written justification to confirm that (b)(4) testing of the nitrogen generated in-house ensured the nitrogen met all applicable standards each time it was used as a product-contact gas in sterile injectable and oral inhalation drugs. Drugs that require a nitrogen overlay include all lots of Lidocaine/Epinephrine Injection, Bupivacaine/Epinephrine Injection, and Lorazepam Injection. Examples of drugs manufactured with nitrogen generated in-house are Lidocaine HCl 1%/Epinephrine Bitartrate 10 mcg/mL Injection USP, 10 mL, SDV, lot 2603001; and Lorazepam Injection USP, 2 mg/mL, lot 2510002.
C. 自产氮气的(b)(4)检测，无法证实每次将氮气作为无菌注射药品、口服吸入药品的产品接触气体使用时，氮气均满足全部适用标准，相关书面论证依据不足。需要氮封保护的药品包括所有批次利多卡因/肾上腺素注射液、布比卡因/肾上腺素注射液、劳拉西泮注射液。使用自产氮气生产药品示例：USP 1%盐酸利多卡因/10mcg/mL重酒石酸肾上腺素注射液，10mL单剂量西林瓶，批号2603001；USP劳拉西泮注射液，2mg/mL，批号2510002。

D. Manufacturing personnel do not (b)(4) test the (b)(4) attached to ISO 5 Filling Line (b)(4). There is no scientific justification for the (b)(4) replacement interval for this point-of-use nitrogen (b)(4).
D. 生产人员未对安装在ISO5灌装线(b)(4)的(b)(4)开展(b)(4)测试。该终端氮气(b)(4)的更换周期无科学依据。

E. The firm did not conduct ID tests or any other analyses on Ultra High Purity (UHP) Nitrogen, lot (b)(4), that was accepted based on supplier COA. This is a product-contact gas used during production of Bupivacaine Hydrochloride 0.5%/Epinephrine Bitartrate 5 mcg/mL Injection, 10 mL vials, lot 2608001.
E. 公司仅依据供应商COA接收超高纯氮气（UHP）批号(b)(4)，未开展鉴别试验或其他分析检测。该氮气为生产0.5%盐酸布比卡因/5mcg/mL重酒石酸肾上腺素注射液，10mL西林瓶，批号2608001所用的产品接触气体。

F. Operators confirmed the (b)(4) of the (b)(4) they attach to the connection point for UHP Nitrogen cylinders in February 2026. Engineering technicians remove the (b)(4) when not in-use and install it when requested by production personnel. Technicians used the (b)(4) in August 2026 without performing a (b)(4) test. There is no written justification for the (b)(4) test interval. Operators (b)(4) gas from UHP Nitrogen cylinder, lot (b)(4) (b)(4), during production of Bupivacaine Hydrochloride 0.5%/Epinephrine Bitartrate 5 mcg/mL Injection, 10 mL vials, lot 2608001.
F. 操作人员确认，2026年2月将(b)(4)安装至超高纯氮气钢瓶接口处。工程技术员在不使用时拆下(b)(4)，生产需要时再进行安装。2026年8月技术员使用该(b)(4)前未开展(b)(4)测试。(b)(4)测试周期无书面论证依据。操作人员在生产0.5%盐酸布比卡因/5mcg/mL重酒石酸肾上腺素注射液，10mL西林瓶，批号2608001期间，从超高纯氮气钢瓶（批号(b)(4)(b)(4)）取用(b)(4)气体。

Ethylene Glycol and Diethylene Glycol (b)(4) Testing

乙二醇与二甘醇(b)(4)检测

G. Your firm did not perform all specific identity tests for Propylene Glycol, lot (b)(4) and Polyethylene Glycol 400, lot (b)(4). Also, your SOP titled (b)(4).LAB.0025-Sample Pooling Strategy for Diethylene Glycol and Ethylene Glycol (DEG/EG), effective 21 Oct 2025, instructs personnel to pool (b)(4) for testing of high-risk drug components. These high-risk components were used in the manufacturing of Lorazepam Injection USP, 2 mg/mL, lot 2510001 (first distribution 12/02/25), lot 2510002 (first distribution 12/01/25), and 2511001 (first distribution 05/11/26).
G. 贵公司未对丙二醇批号(b)(4)、聚乙二醇400批号(b)(4)完成全部专属鉴别试验。此外，贵公司SOP编号(b)(4).LAB.0025《二甘醇与乙二醇（DEG/EG）样品合并检测策略》，生效日期2025年10月21日，规程要求人员对高风险药品辅料合并(b)(4)样品开展检测。这些高风险辅料用于生产USP劳拉西泮注射液2mg/mL，批号2510001（首次分销：2025年12月02日）、批号2510002（首次分销：2025年12月01日）、批号2511001（首次分销：2026年05月11日）。