FDA就β-内酰胺交叉污染等问题向百特Round Lake工厂发出警告信

2026年10月20日，FDA发布了Baxter International Inc.（NYSE: BAX）的警告信：信中指控该公司伊利诺伊州Round Lake无菌注射剂工厂存在严重cGMP违规，涉及头孢菌素类抗生素与其他无菌注射剂隔离不足、反复发生β-内酰胺交叉污染，无菌灌装线未经验证且常规生物指示剂失败，微粒检查缺陷，以及无菌检验失败被不当判定无效。FDA在信中警告：未解决的违规可能引发法律行动、扣留出口证书或阻止与该厂相关的新药申请获批。警告信公开当日，Baxter股价下跌4.84%，收报23.78美元。如下：

检查对象：Baxter Healthcare Corporation（百特医疗有限公司）

检查日期：2026 年 3 月 23 日 至 4 月 2 日

483回复提交时间：2026 年 4 月 23 日

FDA 警告信日期：2026 年 9 月 29 日

This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.

本警告函告知贵方，美国食品药品监督管理局（FDA）在对贵厂区开展检查期间发现了严重违规情形。请立即整改本函所述违规项，确保调配充足资源，彻底整改违规问题并防止问题再次发生。本函并未穷尽贵厂区存在的全部违规事项。贵公司有义务确保自身遵守联邦法律全部要求，包括FDA相关法规。若未能充分整改违规项，FDA可不经另行通知即采取监管措施或法律行动，包括但不限于查封以及禁令。

FDA Inspection

FDA检查

Violations were observed and documented during an inspection of your drug manufacturing facility, Baxter Healthcare Corporation, FDA Establishment Identifier (FEI) 1416980, at 25212 W Illinois Route 120, Round Lake, from March 23 to April 2, 2026. This inspection was conducted under FDA's statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.

FDA于2026年3月23日至4月2日，对位于朗莱克市伊利诺伊120号公路西段25212号的百特医疗药品生产厂区（FDA机构编号FEI：1416980）开展检查，检查期间发现并记录违规事项。本次检查依据FDA法定职权以及公共卫生职责开展，旨在保护公众远离不安全、无效以及质量低劣的药品。

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

本警告函汇总了成品药品现行良好生产规范（CGMP）法规方面的严重违规情况。详见《联邦法规汇编》第21篇第210和211部分（21 CFR 210、211部分）。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

由于贵方生产、加工、包装或储存所用的方法、设施或控制措施不符合CGMP要求，根据《联邦食品、药品和化妆品法案》（FD&C法案）第501(a)(2)(B)条，即《美国法典》第21编351(a)(2)(B)条的定义，贵公司药品属于掺假药品。

We reviewed your April 23, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

我方已详细审阅贵方2026年4月23日针对FDA 483表提交的答复，并确认收到贵方后续往来信函。

Violations of the Federal Food, Drug, and Cosmetic Act

《联邦食品、药品和化妆品法案》违规事项

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

以下为本次检查及审核过程中发现的违规项。特此提醒，本清单并未穷尽贵厂区全部违规问题。

1. Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(c)).

1. 贵公司未在划定的、面积充足的区域内开展生产操作，未设置独立或划定区域以及其他必要的控制系统，以防止污染或混淆（21 CFR 211.42(c)）。

You manufacture various injectable drugs products including cephalosporins (a beta-lactam drug product) and (b)(4) drug products at your facility. You failed to ensure complete and comprehensive separation of cephalosporin and (b)(4) drug products in this shared facility.

贵厂区生产多种注射剂，包括头孢类（β-内酰胺类药品）以及(b)(4)类药品。在该共用厂区内，贵方未能实现头孢类药品与(b)(4)类药品完全、充分隔离。

Lack of Complete and Comprehensive Separation

未实现完全、充分隔离

Your facilities and controls were inadequate to prevent the conditions that would allow for cephalosporin contamination of (b)(4) drugs.

贵方设施与控制措施存在不足，无法杜绝(b)(4)类药品被头孢类物质污染的风险。

Your building is divided into (b)(4) beta lactams, (b)(4) production. These building segments are separated by a physical wall that you consider to be fully sealed, along with dedicated HVAC units.

该厂房划分为(b)(4)β-内酰胺生产区域、(b)(4)生产区域。上述区域通过实体隔墙（贵方称该隔墙完全密封）以及独立暖通空调系统分隔。

However, since January 2025, your environmental monitoring (EM) program used to monitor containment of beta-lactam drug products has detected cephalosporin in several instances and in multiple areas of the (b)(4) side of the building.

但自2025年1月起，用于监控β-内酰胺类药品隔离管控效果的环境监测（EM）项目，已多次在厂房(b)(4)侧多个区域检出头孢类物质。

Inadequate Cephalosporin Monitoring

头孢类物质监测工作存在缺陷

While your monitoring program detected recurring cross-contamination, it was inadequate to promptly detect loss of containment and cephalosporin contamination in your facility. For example:

尽管监测项目多次检出交叉污染，但该监测体系不足以快速发现隔离失效以及厂区内的头孢污染问题，例如：

• EM sampling was insufficient in both number and location.
环境监测取样的点位数量与布设位置不足。

• Swab sampling qualification was inadequate to assure low-level recovery.
擦拭取样的方法学确认存在缺陷，无法保证低浓度水平的回收率。

• Samples were evaluated beyond established solution stability time allowances.
样品检测超出规定的溶液稳定时限。

These inadequacies create risk for underrepresentation of true contamination hazards throughout your facility, create potential for false negative results, and inhibit meaningful data collection upon which your quality unit (QU) can make sound risk-based decisions.

上述缺陷会导致无法如实反映厂区真实污染风险，存在假阴性结果风险，也不利于采集有效数据支撑质量部门（QU）做出可靠的基于风险的决策。

A rigorous monitoring program is essential for facility qualification, early detection of contamination hazards, and timely corrective action and preventive action (CAPA).

一套严谨的监测方案，对于设施确认、污染风险早期识别、及时实施纠正与预防措施（CAPA）至关重要。

In addition, your testing of (b)(4) drug products for potential contamination consisted of a single unit regardless of batch size. However, contamination is generally nonuniformly distributed. Results obtained from testing a small sample size are unlikely to detect contamination that may exist in a batch exposed to the contamination hazards identified at your firm. Consequently, substantial residual uncertainty remains regarding the actual variability of contamination that may exist in batches you produce.

此外，无论批量大小，贵方仅抽取1支(b)(4)类药品进行污染排查。但污染通常呈非均匀分布。小样本检测很难检出已暴露于贵方所识别污染风险中的批次里存在的污染。因此，贵方所生产批次中实际污染波动情况仍存在很大不确定性。

We also note that you mistakenly discarded multiple failing cephalosporin environmental samples before further analysis could be conducted.

我方同时注意到，贵方在开展进一步检测之前，误丢弃多份检出阳性的头孢环境样品。

In your response, you commit to strengthen investigations into positive cephalosporin findings, create a tracking form to help prevent missed samples, and improve low-level recovery. Your response also indicates that significant uncertainty remains regarding the causes of the recurring findings of facility contamination. You indicate that personnel movement was a weakness in your containment strategy while adding that personnel movement is likely not the sole contributing factor.

贵方在答复中承诺加强头孢阳性结果的调查工作，建立跟踪表单避免样品漏检，并优化低浓度回收率。答复同时说明，反复检出厂区污染的根本原因仍存在较大不确定性。贵方提出人员流动是隔离管控策略中的薄弱点，但同时表示人员流动大概率并非唯一诱因。

Your response is inadequate because it fails to adequately address how you will ensure complete and comprehensive separation. You also failed to thoroughly reevaluate your original risk management decisions, including supportive risk assessments and associated risk controls, to ensure prevention of beta-lactam cross-contamination. Although your cephalosporin and (b)(4) areas exist within the same external building structure that you claim is completely and comprehensively separated by a (b)(4), it is essential that your design completely precludes any potential for incidental air, personnel, materials, equipment, or other interaction that could be a vector of contamination. A rigorous quality risk management program should comprehensively assess the design and determine if it provides as much protection against cross-contamination as is achieved by manufacturing in a separate building.

贵方答复不充分，未能充分说明如何实现完全、充分隔离；也未全面重新评估原有风险管理结论，包括配套风险评估以及相关风险控制措施，以防范β-内酰胺交叉污染。头孢区域与(b)(4)区域处于同一栋主体厂房内，贵方称二者通过(b)(4)实现完全隔离，但设施设计必须杜绝空气、人员、物料、设备以及其他可作为污染媒介的交互风险。一套严谨的质量风险管理方案应当全面评估该设计，判断其防交叉污染能力是否等同于独立厂房生产模式。

We note that data shared during our recall discussions revealed additional cephalosporin contamination events in the (b)(4) area, including as recently as (b)(4).

我方注意到，在召回沟通会议中提供的数据显示，(b)(4)区域还发生过其他头孢污染事件，最近一次发生于(b)(4)。

Contamination of (b)(4) with beta-lactam drugs presents a serious risk to patient safety, including potential life-threatening (b)(4). (b)(4) responses can occur in susceptible patients exposed to (b)(4) beta-lactams. Therefore, no safe level of beta-lactam contamination has been determined to be a tolerable risk.

(b)(4)类药品被β-内酰胺药品污染将带来严重患者安全风险，包括可危及生命的(b)(4)。易感患者接触(b)(4)β-内酰胺物质后可发生(b)(4)反应。因此，目前不存在可接受的β-内酰胺污染安全阈值。

In response to this letter, provide:

请针对本函提交以下资料：

1. A comprehensive, independent evaluation of the sufficiency of facility modifications implemented in an attempt to achieve complete and comprehensive separation (e.g., physical wall, dedicated air handling) between cephalosporin and (b)(4) areas.
一份独立、全面评估报告，评估为实现头孢区域与(b)(4)区域完全隔离而实施的设施改造（例如实体隔墙、独立空气处理系统）是否充分有效。

2. An updated comprehensive, independent risk assessment of all beta-lactam contamination hazards with respect to your procedures, equipment, and facilities, including but not limited to:

一份更新后的独立、全面风险评估，覆盖与规程、设备、设施相关的全部β-内酰胺污染风险，包括但不限于：

identification of all contamination hazards (e.g., personnel, material, air systems, infrastructure vulnerabilities);

识别全部污染危害源（例如人员、物料、空气系统、基础设施薄弱点）；

hazard identification using formal hazard identification tools;

使用规范危害识别工具开展危害识别；

expanded risk-based EM including appropriate, scientifically justified, sampling methods, locations, and frequencies (e.g., inside production rooms, equipment surfaces, walls, contractor and operator garments, boots, shared forklifts trucks, shared lab cabinet, other potential cross-contamination locations), with consideration of all associated containment elements;

拓展基于风险的环境监测，配套科学合理、经过论证的取样方式、点位与频次（例如生产房间内部、设备表面、墙面、外包人员与操作人员工服、鞋靴、共用叉车、共用实验室柜以及其他潜在交叉污染点位），并考虑全部相关隔离要素；

more responsive systems to vigilantly respond to any contamination, including enhanced trending systems;

建立更灵敏的污染响应体系，包括强化趋势分析系统；

personnel flow and material flow (comprehensive mapping of all such potential interactions between all facilities that may introduce a potential hazard);

人员流向与物料流向（完整梳理所有厂区内可引入风险的交互路径）；

scientifically justified sampling of (b)(4) finished drug product batches;

对(b)(4)成品批次实施经过科学论证的取样方案；

specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment.
明确CAPA建议，全面整改风险评估识别出的设计与控制风险。

3. A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to design (e.g., facility changes) and explain how this CAPA plan will robustly remediate your deficiencies. Include a description of any residual risk that may remain following these remediations, and describe whether it enables risk acceptance. Also include a commitment to implement thorough change effectiveness activities and to revisit the risk assessment when necessary.

一份带时间节点的详细整改计划，落实污染风险评估发现项。说明具体可落地的设计优化方案（例如设施改造），解释该CAPA方案如何稳健整改缺陷。说明整改完成后仍可能存在的剩余风险，并说明该风险是否可接受。同时承诺开展充分的变更有效性评估，并在必要时重新开展风险评估。

4. A comprehensive assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm's documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous (ALCOA) records throughout your operation.
全面评估生产与实验室全流程文件体系，识别文件记录方面的缺陷。配套详细CAPA方案，全面整改文件管理，确保全流程记录满足可归属、清晰、完整、原始、准确、同步（ALCOA）原则。

5. Full investigations and data pertaining to any failing cephalosporin samples that were discarded since August 2024, including but not limited to sampling location, date, recovery amount, and any extra testing that was to be performed.
2024年8月以来所有被丢弃的头孢阳性样品的完整调查资料与原始数据，包括但不限于取样点位、取样日期、检出量、计划开展的附加检测项目。

2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)). Your firm also failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.42(c)(10)).

2. 贵公司未建立并执行合适的书面规程，用以防止标示无菌的药品受到微生物污染，规程应包含所有无菌工艺与灭菌工艺的验证（21 CFR 211.113(b)）。同时，无菌生产区域未在划定的、面积充足的区域内操作，未设置独立/划定区域或其他必要控制系统防止污染、混淆（21 CFR 211.42(c)(10)）。

You operate (b)(4) processing lines used to aseptically manufacture sterile injectable drug products for the U.S. market. Your (b)(4) were inadequately validated to ensure that they were capable of consistently (b)(4) interior surfaces of your (b)(4) lines in preparation for aseptic production. In addition, your aseptic process simulations did not sufficiently represent worst-case conditions, and you lacked adequate sampling of your ISO 5 (Grade A) area.

贵方运行(b)(4)生产线，为美国市场无菌注射剂开展无菌生产。贵方(b)(4)的验证不充分，无法保证其能够稳定对(b)(4)生产线内表面实施(b)(4)处理，为无菌生产做准备。此外，无菌工艺模拟试验未能充分代表最差条件，ISO 5（A级）区域取样不足。

Biological Indicator Recoveries and Inadequate (b)(4) Validation

生物指示剂检出阳性，(b)(4)验证存在缺陷

Inadequacies in your (b)(4) process were demonstrated through a trend of routine recoveries of biological indicator (BI) growth at the completion of (b)(4) cycle re-qualification (validation) runs since (b)(4).

自(b)(4)起，多次(b)(4)周期再确认（验证）结束后常规检出生物指示剂（BI）长菌，该趋势证明贵方(b)(4)工艺存在缺陷。

Notably, your acceptance criteria were inappropriate in that they allowed routine recovery of multiple BI survivors per re-qualification run. An adverse trend of numerous positive BIs were identified in multiple re-qualification cycles across multiple (b)(4) lines. For example, for line (b)(4), positive BIs occurred at numerous locations ((b)(4) of (b)(4) locations) and the positive findings included multiple replicates per location ((b)(4) recoveries of (b)(4) replicates). In addition, other lines had similar substantial findings of positive BIs. However, you considered all re-qualification studies to be acceptable and did not further evaluate the excessive variability of your (b)(4), including the potential impact to product. These significant recurring BI failures indicate poor (b)(4) method efficacy and require further investigation.

值得注意的是，贵方可接受标准设置不合理，允许单次再确认周期检出多处生物指示剂存活菌。多条(b)(4)生产线的多个再确认周期均出现大量BI阳性的不良趋势。例如(b)(4)号线，多个点位检出BI阳性（在(b)(4)个点位中占(b)(4)处），同一点位多个平行样阳性（(b)(4)份平行样检出(b)(4)份阳性）。其他产线同样存在大量BI阳性结果。但贵方判定全部再确认试验合格，未进一步评估(b)(4)工艺过大的波动，包括对产品的潜在影响。该反复出现的BI不合格问题说明(b)(4)工艺效果不佳，需要深入调查。

We also noted additional deficiencies in your (b)(4) reliability. For example:

我方还发现(b)(4)可靠性存在其他缺陷，例如：

• You lacked adequate scientific justification for BI locations.
生物指示剂放置点位缺乏充分科学论证。

• You allowed repetition of re-qualification cycles without proper investigation into observed BI growth.
检出BI长菌后，未开展适当调查即重复开展再确认周期。

• You did not align with technical references you cited in your procedures.
实际操作与规程中引用的技术参考资料不一致。

We note that you recovered (b)(4), from an (b)(4) inside your (b)(4) during production.

我方注意到，在生产期间，于(b)(4)内部的一处(b)(4)检出(b)(4)。

In your response, you commit to engaging a (b)(4) to help improve (b)(4), revising acceptance criteria to align with industry standards, and initiating non-conformance reports to investigate the observed BI growth. You also commit to evaluating alternative (b)(4) technology.

贵方答复承诺聘请(b)(4)协助优化(b)(4)，修订可接受标准使其符合行业标准，启动不符合项报告调查BI长菌情况；同时承诺评估替代(b)(4)技术。

Your response is inadequate in that it does not provide sufficient detail or supporting documentation to describe how adequate (b)(4) will be achieved during the interim period prior to completion of long-term remediation.

贵方答复不充分，未提供足够细节与佐证文件，说明在长期整改落地前的过渡期内如何保障(b)(4)效果达标。

Incomplete exposure of interior surfaces to (b)(4) compromises (b)(4) effectiveness and places your (b)(4) environment at risk. The (b)(4) (Grade A) area is critical because sterile products are exposed during aseptic production and therefore vulnerable to contamination if operations are not well designed and diligently controlled. Aseptic processing operations should be designed and executed to minimize exposure of sterile articles to potential contamination hazards in the manufacturing operation. Flaws in the design or control of cleanrooms and aseptic processing operations can enable entry of contaminants into the critical (b)(4) processing area and lead to product contamination.

内表面未能充分暴露于(b)(4)介质会降低(b)(4)效果，使(b)(4)环境面临污染风险。(b)(4)（A级）区域至关重要，无菌产品在无菌生产过程中暴露，若工艺设计不合理、管控不到位，极易受到污染。无菌工艺的设计与执行应尽量减少无菌物品在生产过程中接触潜在污染风险。洁净室与无菌工艺的设计、管控缺陷会造成污染物进入关键(b)(4)生产区域，引发产品污染。

Inadequate Aseptic Process Simulation

无菌工艺模拟试验缺陷

The intervention of (b)(4) was simulated approximately (b)(4) times during a media fill, but production records indicate a significantly higher occurrence of this intervention.

在培养基灌装试验中，(b)(4)干预操作仅模拟约(b)(4)次，但生产记录显示该类干预的实际发生频次远高于此。

In your response you commit to updating the minimum number of (b)(4) simulations to (b)(4) based on your 2026 retrospective review, which only covered approximately (b)(4). Your response is inadequate as it does not ensure worst-case production activities and conditions are challenged across all (b)(4) lines. If a media fill program fails to incorporate contamination risk factors and closely simulate actual drug production, the state of process control and assurance of sterility cannot be accurately assessed.

贵方答复承诺基于2026年回顾性评估，将(b)(4)模拟最低次数更新为(b)(4)，但该回顾评估仅覆盖约(b)(4)。答复不充分，无法保证全部(b)(4)产线都经过最差生产操作与条件的挑战。若培养基灌装方案未纳入污染风险因素、无法真实模拟实际药品生产，则无法准确评估工艺受控状态以及无菌保障水平。

Inadequate Environmental Monitoring

环境监测缺陷

Your (b)(4) processing lines include critical operational steps conducted in (b)(4). However, there was only a (b)(4) in one of these (b)(4). In addition, surfaces were not monitored for microbiological contamination.

贵方(b)(4)生产线包含在(b)(4)内开展的关键操作步骤，但其中一处(b)(4)内仅设置了(b)(4)；同时未进行表面微生物监测。

Vigilant and responsive environmental monitoring programs provide meaningful information on the state of control of the aseptic processing operation and enable an early warning system that identifies emerging contamination hazards before sterility is compromised.

灵敏、及时响应的环境监测体系，能够反馈无菌工艺的受控状态，形成预警机制，在无菌状态被破坏前识别新增污染风险。

Inadequate Airflow

气流存在缺陷

Although your (b)(4) configurations can vary (e.g., (b)(4) bag capacity, (b)(4) configuration), you lacked airflow visualization studies in (b)(4) of your (b)(4) lines. In addition, your airflow visualization studies were insufficient (e.g., worst-case (b)(4) conditions).

尽管(b)(4)形态存在差异（例如(b)(4)袋容量、(b)(4)构型），但贵方未对(b)(4)生产线的(b)(4)开展气流可视化研究；且已开展的气流可视化研究不充分，未覆盖最差(b)(4)工况。

We note that you have had a history of sporadic sterility test positives since 2013 (testing is routinely performed in a (b)(4)) and persistent particulate contamination issues.

我方注意到，自2013年起贵方就断续出现无菌检查阳性（常规在(b)(4)内开展无菌检测），且长期存在微粒污染问题。

Your airflow visualization studies also revealed substantial turbulence in your (b)(4), in which critical process steps are performed. Your firm acknowledged turbulent non-unidirectional airflow within your (b)(4), which houses processing equipment.

气流可视化试验同时显示，开展关键工艺步骤的(b)(4)内存在明显紊流。贵方承认放置生产设备的(b)(4)内部气流紊乱，非单向流。

Our overall findings indicate significant deficiencies in the design of your aseptic processing operation. Your current equipment, process, and airflow design pose excessive contamination risk.

综合检查发现，贵方无菌工艺设计存在严重缺陷。现有设备、工艺、气流设计带来过高污染风险。

Turbulent airflow may be appropriate for a (b)(4) that does not house aseptic processing equipment. In contrast, your firm uses (b)(4) that include processing line equipment.

紊流适用于未放置无菌生产设备的(b)(4)。但贵方所使用的(b)(4)内部放置生产线设备。

A strong quality system is essential to oversee design and construction of aseptic processing lines, cleanrooms, and supporting utilities, and to ensure ongoing proper operational control to safeguard against contamination hazards throughout the facility lifecycle.

完善的质量体系对于监督无菌生产线、洁净室以及配套公用工程的设计和建造至关重要，保障设施全生命周期内持续受控、防范污染风险。

Well-designed aseptic processing (b)(4) represent a significant technological advance over traditional operational designs. Because all technologies have failure modes, it is essential to implement a robust design and control program that enables an ongoing state of control.

设计良好的无菌(b)(4)相比传统操作模式属于重大技术升级。但任何技术都存在失效模式，因此必须建立稳健的设计与管控方案，维持持续受控状态。

See FDA's guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at

https://www.fda.gov/media/71026/download.

请参考FDA指南文件《无菌工艺生产的无菌药品——现行良好生产规范》，指导贵方在无菌药品生产中满足CGMP要求，文件链接：

https://www.fda.gov/media/71026/download。

In your response, you commit to improving your EM program and performing airflow visualization studies on all of your lines. You also state that you will use data from these studies to identify locations for BIs and EM.

贵方答复承诺优化环境监测方案，对全部产线开展气流可视化研究，并利用研究数据确定生物指示剂与环境监测点位。

Your response is inadequate as you lack a commitment to upgrade your manufacturing infrastructure, including equipment replacement, as part of your long-term remediation plan. In addition, the timeline for implementation of additional viable air monitoring in the (b)(4) is unclear.

贵方答复不充分，长期整改计划中未承诺升级生产基础设施（含设备更换）；同时，在(b)(4)内新增浮游菌监测的实施时间节点不明确。

In response to this letter, provide:

请针对本函提交以下资料：

1. A detailed program for designing, validating, maintaining, controlling and monitoring each of your (b)(4) that includes vigilant monitoring to ensure an ongoing state of control.
一套详细方案，覆盖每一台(b)(4)的设计、验证、维护、控制与监测，配套灵敏监测手段以维持持续受控状态。

2. A comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to:

一份独立、全面风险评估，覆盖无菌工艺、设备、设施相关全部污染风险，包括但不限于：

all human interactions within the (b)(4) area (e.g., risk reduction or elimination of manual interventions wherever possible);

(b)(4)区域内所有人为操作干预（例如尽可能降低或消除人工干预风险）；

equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficiency of space for operations;

设备适用性（可靠性、工艺能力、人机工程、摆放位置）以及操作空间充足性；

air quality in the (b)(4) area including, but not limited to, air unidirectionality;

(b)(4)区域空气质量，包括单向流状态；

facility layout;

设施布局；

personnel flow and material flow (movement throughout all rooms used to conduct and support sterile operations, and all material transfers);

人员流向与物料流向（所有用于无菌生产及配套支持的房间内的人员移动、全部物料转运）；

(b)(4) practices and procedures (e.g., (b)(4) efficacy, appropriate (b)(4) and configuration);

(b)(4)操作规程（例如(b)(4)效果、合适的(b)(4)及构型）；

specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment.
明确CAPA建议，全面整改风险评估识别的设计与控制风险。

3. A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe comprehensive improvements to be made to aseptic processing operation design and control at your facility and explain how this CAPA plan will systematically remediate your deficient sterile manufacturing operations. Include detailed changes to the design of both your aseptic processing lines and cleanrooms. Your action plan should include both an interim plan as well as long-term steps to fully remediate your facility, equipment, and process design.
一份带时间节点的详细整改计划，落实污染风险评估发现项。说明厂区无菌工艺设计与管控的全套优化方案，解释该CAPA如何系统性整改有缺陷的无菌生产活动，包含无菌生产线与洁净室设计的详细变更内容。行动计划应同时包含过渡期方案以及长期措施，彻底整改设施、设备与工艺设计缺陷。

4. An independent review, detailed report, CAPA, and timelines for remediation of your (b)(4) methods (e.g., (b)(4) parameters, optimized airflow, improved surface exposure). This comprehensive, independent analysis should incorporate any differences between the design and operation of each (b)(4) and its processing equipment (e.g., dimensions, orientation, (b)(4) design, air volume, (b)(4), (b)(4) bowls, bag capacity, etc.).
对(b)(4)工艺方法开展独立审核，提交详细报告、CAPA以及整改时限（例如(b)(4)参数、优化气流、提升表面暴露效果）。该独立全面分析需考虑每台(b)(4)及其配套生产设备在设计、运行上的差异（例如尺寸、摆放朝向、(b)(4)设计、风量、(b)(4)、(b)(4)槽体、袋容量等）。

5. An independent, comprehensive evaluation of airflow unidirectionality in your aseptic processing operations. Ensure smoke studies are conducted under dynamic conditions with thorough and complete assessments of aseptic processing line airflow unidirectionality, including the impact of aseptic interventions, worst-case (b)(4) pattern, and dynamic interactions with the surrounding cleanroom. Conduct these smoke studies after you remediate your aseptic operation and using proper practices (e.g., (b)(4) media) to appropriately visualize airflow.
独立全面评估无菌工艺的单向流状态。需在动态条件下开展烟雾试验，完整评估无菌生产线单向流，包含无菌干预操作、最差(b)(4)工况、与周边洁净室的动态交互带来的影响。烟雾试验应在无菌工艺整改完成后实施，使用合适介质（例如(b)(4)介质）实现气流可视化。

6. A comprehensive, independent review of your process simulation (e.g., media fill) program to ensure accurate simulations of commercial aseptic manufacturing operations, including, but not limited to, appropriate incorporation of worst-case conditions.
独立全面审核工艺模拟（培养基灌装）方案，确保可以真实模拟商业化无菌生产，包括合理纳入最差条件。

7. A summary table of all EM (includes surfaces, air, and (b)(4)) results within your (b)(4) lines that revealed microbial growth since January 1, 2023. Include line sample location, date, colony forming unit (CFU) count, microorganism identification, and any associated investigations.
汇总表格，列出自2023年1月1日起，(b)(4)生产线内所有检出微生物生长的环境监测（含表面、空气、(b)(4)）结果，包含产线、取样点位、日期、菌落数（CFU）、菌种鉴定结果以及对应的调查记录。

3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

3. 贵公司未建立实验室控制体系，该体系应包含经过科学论证、合适的质量标准、规范、取样方案以及检验规程，保证组分、药包容器、密封件、中间产品、标签以及成品符合鉴别、效价、质量、纯度相关标准（21 CFR 211.160(b)）。

Your manual visual inspection program was inadequate to reliably detect defects and ensure your sterile injectable drug products were essentially free of visible particulates.

人工灯检方案存在缺陷，无法稳定检出缺陷，无法保证无菌注射剂基本无可见微粒。

For example, operators performing (b)(4) visual inspection were not properly qualified, as evidenced by the following:

例如，开展(b)(4)灯检的操作人员资质确认不到位，证据如下：

• Operators were not appropriately challenged to ensure they were capable of reliably detecting particulates within the lower end of the visible spectrum.
未设置合适的考核样品以验证操作人员能够稳定检出可见粒径下限附近的微粒。

• Particulates in challenge kits were excessively large (e.g., greater than (b)(4) microns), approximately (b)(4) times larger than what operators should be capable of reliably detecting.
考核样品包内微粒尺寸过大（例如大于(b)(4)微米），约为操作人员应稳定检出粒径的(b)(4)倍。

• Operators' rate of inspection was excessively fast (e.g., (b)(4) per unit) and did not align with the standards referenced in your procedures.
操作人员检查速度过快（例如每支(b)(4)），与规程引用标准不符。

Notably, you also demonstrated poor detection rates when you used significantly longer inspection times during Acceptable Quality Limit (AQL) sampling.

值得注意的是，即使在可接收质量限（AQL）取样时大幅延长检查时长，检出率依旧偏低。

Your approach to identifying product defects compromises reliable detection and the quality of data inputs to support batch release and CAPA decisions made by your quality unit.

贵方的缺陷检出方式降低缺陷检出可靠性，影响质量部门用于批放行、CAPA决策的数据质量。

In addition, the significant particulate matter complaints received between 2023 to 2025 indicate an inadequate visual inspection program. For example, on May 9, 2025, after testing a returned cefazolin complainant sample you confirmed foreign particulate contamination was consistent with cardboard (approximately (b)(4) mm). Your investigation concluded that inadequacies of visual inspection were a contributing cause, but you did not implement sufficient CAPA to ensure remediation of your visual inspection program.

此外，2023至2025年间收到大量微粒相关投诉，证明目检方案存在缺陷。例如2025年5月9日，对退回的头孢唑林投诉样品检测后，确认外来微粒为纸板材质（约(b)(4)毫米）。贵方调查结论认定目检缺陷是诱因之一，但未落实充分CAPA整改目检体系。

Your investigation specifically cited potential for compromised product quality and potential patient safety risks, but stated that field action was not warranted. We acknowledge that on July 17, 2026, you agreed to voluntarily recall cefazolin, Lot LD175708, only after the Agency contacted you.

贵方调查报告明确提及产品质量受损、患者安全存在潜在风险，但判定无需采取市场处置措施。我方确认，直至FDA联系贵方之后，贵方才于2026年7月17日同意主动召回头孢唑林LD175708批次。

In your response you commit to enhancing your visual inspection program including performing probability of detection (PoD) studies using the (b)(4) per unit inspection duration.

贵方答复承诺优化目检方案，采用每支(b)(4)的检查时长开展检出概率（PoD）研究。

Your response is inadequate. You indicate that data from post-market complaint evaluations and retain sample reviews confirm that your controls remain effective. However, you have identified particulate matter in retain and complaint samples after product was released. In addition, your response does not adequately address the spike in particulate matter defects from 2024 ((b)(4) defects) to 2025 ((b)(4) defects). There remains a lack of assurance that your injectable drug products are essentially free from visible particulates while you work on long-term remediation.

贵方答复不充分。贵方称上市后投诉评估、留样复核数据证明现有控制措施持续有效，但产品放行后，留样与投诉样品中仍检出微粒。同时答复未充分说明2024年（(b)(4)起缺陷）至2025年（(b)(4)起缺陷）微粒缺陷数量激增的问题。在长期整改落地期间，依旧无法保证注射剂基本不含可见微粒。

Visual detection of particulates is a probabilistic process that depends on, among other things, ensuring that visible particulates can be reproducibly detected by trained personnel with appropriate visual acuity. At a minimum, personnel should reliably be capable of detecting particulates of (b)(4) microns or greater at a (b)(4)% probability of detection. It is important that any visible particulate contamination is appropriately evaluated and investigated. Particulates in injectable products should be avoided through appropriate preventive measures built into your design and production controls. When categorizing any visible particles, extrinsic or foreign matter should receive special attention, as it may indicate possible microbial contamination. Extrinsic or foreign particulate contamination should occur very infrequently and trigger a thorough investigation and appropriate CAPA.

微粒目视检出属于概率性事件，核心是经过培训、视力合格的人员能够稳定重现检出可见微粒。最低要求是操作人员能够以(b)(4)%的检出概率稳定检出(b)(4)微米及以上微粒。所有可见微粒污染均需要合理评估与调查。应当在设计与生产管控中设置预防性措施，避免注射剂出现微粒。对可见微粒分类时，外来异物需要重点关注，该类异物可能提示存在微生物污染。外来异物污染应极少发生，一旦出现必须启动全面调查并落实合适CAPA。

In response to this letter, provide:

请针对本函提交以下资料：

1.A comprehensive, independent assessment and remediation plan of your systems for the visual inspection of sterile injectable drugs for defects, including the presence of particulate matter. The assessment should include acceptance and rejection criteria, personnel training, supervision, equipment and personnel qualification, equipment maintenance, and process validation, and the procedures governing them. Also include product-specific knowledge, process experience (e.g., thorough assessment of the spike of (b)(4) particulate matter defects in 2025), deviation investigation analysis, and recall/complaint data. Provide your detailed remediation action plan that includes dates by which each remediation activity will be completed and a periodic independent reassessment of the plan's effectiveness. Include a summary of the review and recommendations made by your independent consultant.
独立全面评估无菌注射剂缺陷（含微粒）目视检查体系并配套整改计划。评估内容包含合格/不合格判定标准、人员培训、监督管理、设备与人员资质确认、设备维护、工艺验证以及对应的管理规程。同时结合产品特性、工艺经验（例如完整评估2025年(b)(4)类微粒缺陷突增问题）、偏差调查分析、召回与投诉数据。提交详细整改方案，列明每项整改的完成时限，配套定期独立再评估验证整改有效性，并附上独立顾问的审核摘要与建议。

2. A comprehensive, independent assessment of each lot of sterile injectable drugs distributed from your facility that remains within expiry to meet the requirement of being essentially free of visible particles. This comprehensive review should include a review of all relevant in-process and finished product data obtained by your firm including all batch records.
独立全面评估贵厂区已放行、尚在有效期内的所有无菌注射剂批次，确认是否满足基本无可见微粒的要求。该全面复核应覆盖贵方全部相关中间产品、成品数据，包含所有批记录。

3. An interim plan for risk mitigation while you perform broader studies to improve your visual inspection program. Provide a detailed list of your risk mitigations (e.g., sampling plans and methods for your proposed destructive testing).
在开展更大范围研究优化目检方案期间的过渡期风险降低方案，提供详细风险控制措施清单（例如拟实施破坏性检验的取样方案与方法）。

4. 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 (21 CFR 211.192).

4. 无论批次是否已经放行上市，贵公司均未对无法解释的偏差、批次或组分不符合质量标准的情况开展充分调查（21 CFR 211.192）。

There was a pattern of inadequate investigations into critical issues, including leaking drug products and sterility failures.

针对产品泄漏、无菌不合格等重大问题的调查普遍不充分。

Leaking Units

产品泄漏

Your investigations into the "systemic nature" of container-closure integrity failures lacked effective CAPA to address the significantly increased rate of leak defects in your injectable drug products. You did not implement sufficient CAPA to ensure remediation of your final inspection program. Further, since 2023, media fill units were found leaking during incubation and you have received numerous leak complaints for marketed products.

针对包装密封完整性失效的"系统性问题"开展的调查，缺少有效的CAPA来解决注射剂泄漏缺陷率显著上升的问题。贵方未落实充分CAPA整改终检方案。此外，自2023年起，培养基灌装样品在培养期间被发现泄漏，上市产品也收到大量泄漏投诉。

All sterile drugs must be packaged using container-closure systems with robust protection that prevents the ingress of microorganisms. A product's ability to maintain integrity throughout anticipated stresses and external factors during manufacture, storage, distribution, and consumer use is critical to ensure product quality and safety. Loss of container-closure integrity is a direct cause of non-sterility.

所有无菌药品的包装密封系统必须具备可靠防护能力，防止微生物侵入。产品在生产、储存、流通、患者使用全过程承受预期外力与外界影响时，维持包装完整性的能力，是保障产品质量与安全的关键。包装密封完整性丧失是导致非无菌的直接原因。

In your response, you acknowledge that strengthening your investigation system is warranted and you will evaluate whether (b)(4) container closure integrity testing (CCIT) could be an effective layered control. You also commit to a retrospective review of critical non-conformance reports (NCR) and laboratory investigations for the last year.

贵方答复承认有必要强化调查体系，并将评估(b)(4)包装密封完整性检测（CCIT）是否可作为有效的叠加控制手段；同时承诺回顾过去一年的重大不符合项报告（NCR）以及实验室调查记录。

Your response is inadequate. Limiting a retrospective review to (b)(4) lacks adequate scientific justification as your leak trending data illustrated the leak rate has consistently increased annually from 2023 to 2026. You also do not sufficiently address how a lack of highly capable leak detection systems impacts already produced products, or sufficiently detail improvements to your CAPA system. In addition, data from your firm indicates that although leak rate has increased, the number of NCRs opened has decreased.

贵方答复不充分。仅限定回顾(b)(4)的范围缺乏科学依据，泄漏趋势数据显示2023至2026年泄漏率逐年持续上升。答复也未充分说明高灵敏度泄漏检测手段缺失对已生产产品造成的影响，CAPA体系优化细节不足。同时贵方数据显示，泄漏率上升，但开立的不符合项报告数量反而下降。

Sterility Failure

无菌不合格

Your investigation into a 2025 sterility failure for cefazolin, lot (b)(4), assigned the root cause as a non-integral test container. Test records had been signed and dated indicating that container integrity was initially verified. However, after observing turbidity, you subsequently stated in your investigation that container integrity was not verified, classifying it as a "no-test." Without conducting a Phase II investigation, you concluded there was no risk to the manufacturing process or finished product. You invalidated the sterility result without adequate scientific justification and released this lot in July 2025.

贵方对2025年头孢唑林(b)(4)批次无菌不合格的调查，将根本原因判定为检测容器密封失效。检验记录已签字、标注日期，证明初始已确认容器完整性；但检出浑浊后，调查记录改口称未核查容器完整性，归类为"无效检测"。未开展II期调查即判定对生产工艺与成品无风险，在缺乏充分科学依据的前提下判定该无菌结果无效，并于2025年7月放行该批次。

Notably, the same container integrity problem had been observed in the sterility test of (b)(4), lot (b)(4), in (b)(4), which you rejected.

值得注意的是，(b)(4)年(b)(4)批次的无菌检查中，也曾出现相同的容器完整性问题，当时贵方判定该批次不合格。

In addition, a "no-test" designation was used for an (b)(4) cycle requalification attempt that resulted in numerous positive BIs.

此外，某(b)(4)周期性再确认也检出大量BI阳性，同样被标记为"无效检测"。

In your response, you state your belief that the laboratory error of incubating non-integral sterility test containers was the definitive root cause. Your response is inadequate as it fails to address why your lab records described the test container as integral. It also fails to thoroughly address the lack of contemporaneous documentation of any subsequent deviation that could have theoretically occurred. You also commit to implementing a closed membrane sterility testing system in the future, but your proposal does not ensure timely remediation.

贵方答复认为，将密封失效的无菌检查容器放入培养箱属于实验室差错，是确定根本原因。该答复不充分，无法解释为何原始实验室记录写明容器完好；也未充分说明，后续理论上发生的偏差没有同步记录。贵方承诺后续采用封闭薄膜无菌检测系统，但方案无法保障及时整改到位。

Product contamination may go undetected for substantial periods if your firm employs unreliable sterility testing practices. It should also be noted that any positive sterility test result represents a serious CGMP issue that requires a comprehensive investigation into the cause and extent of the problem, and a prompt review of the qualification status of the aseptic process.

若无菌检验操作不可靠，产品污染可能长期无法被检出。同时需要说明，任何无菌检查阳性结果都属于严重CGMP问题，必须全面调查原因与影响范围，并立刻复核无菌工艺确认状态。

Your firm's quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidance documents: Q8(R2) Pharmaceutical Development at

https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at

https://www.fda.gov/media/167721/download, and Q10 Pharmaceutical Quality System at

https://www.fda.gov/media/71553/download.

贵公司质量体系存在缺陷。关于建立并维持符合CGMP的质量体系，请参考FDA指南文件：Q8(R2)药物研发 https://www.fda.gov/media/71535/download；Q9(R1)质量风险管理 https://www.fda.gov/media/167721/download；Q10药物质量体系 https://www.fda.gov/media/71553/download。

In response to this letter, provide:

请针对本函提交以下资料：

1. A comprehensive assessment and remediation plan to ensure your QU is given the authority, independence, and resources to effectively function. The assessment should also include, but not be limited to:

全面评估并提交整改方案，保障质量部门（QU）拥有履职所需的权限、独立性与资源。评估包含但不限于：

a determination of whether procedures used by your firm are robust and appropriate;

判定贵方现行规程是否完善、适用；

provisions for independent QU oversight throughout your CGMP operations to ensure satisfactory procedures and adherence to appropriate practices;

质量部门独立监督全部CGMP活动，保障规程适用、操作合规；

a complete and final review of each batch and its related information before the QU disposition decision, including all investigations;

质量部门做出处置决定前，完整复核每一批次及相关资料，包含全部调查报告；

oversight and approval of discharging of all QU duties to ensure identity, strength, quality, and purity of all products;

监督、批准质量部门所有职责的落地，保障所有产品的鉴别、效价、质量、纯度；

also, describe how executive management supports robust quality assurance at your firm, including, but not limited to, timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control.
同时说明高管层如何支持完善质量保证体系，包括及时调配资源，主动识别、解决新出现的生产质量问题，维持持续受控状态。

2. A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit results, and failures. Provide a detailed action plan to remediate this system, encompassing:

独立全面评估偏差、异常、投诉、超标结果、超限结果、不合格项的整体调查体系。提交详细整改方案，包含：

staff competencies (including use of appropriate subject matter experts);

人员能力（合理使用行业专家）

written procedures;

书面规程

scientific rigor and foundation;

影响范围判定

scope determination;

科学严谨性与依据

root cause evaluations;

根本原因分析

CAPA effectiveness;

CAPA有效性

quality unit lead functional roles, and oversight to ensure all phases of investigations are appropriately conducted;

质量部门牵头职责与监督机制，保障调查全流程规范开展；

and, based on above, detailed systemic improvements to the investigation system.
并基于以上内容，制定调查体系系统性优化细则。

3. An independent third-party assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigation trends, improves the CAPA program when needed, implements final quality unit decisions, and is fully supported by executive management.
由独立第三方评估CAPA体系并出具整改方案，报告需评估CAPA体系是否包含有效的根本原因分析、能够保障CAPA落地有效、分析调查趋势、按需优化CAPA体系、落实质量部门最终决议，且获得高管层充分支持。

4. Provide a comprehensive, independent process capability assessment of your aseptic processing lines, with special emphasis on the capability of critical operational steps, including but not limited to, all container-closure integrity failure modes, and any related CAPA to be initiated in response to the capability assessment.
独立全面评估无菌生产线工艺能力，重点评估关键操作步骤的工艺能力，包含所有包装密封完整性失效模式，并配套基于本次能力评估结果启动的相关CAPA。

5. Perform a holistic assessment across your facilities for similar issues noted at this site and implement appropriate CAPA across your corporate network.
对集团全部厂区开展整体性排查，确认是否存在与本厂区同类问题，并在全集团范围内落实配套CAPA。

CGMP Consultant

CGMP顾问

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm's compliance status with FDA.

基于贵方违规问题的性质，贵方应聘请符合21 CFR 211.34资质要求的顾问，评估生产运营，协助贵方满足CGMP要求。该合格顾问还应对贵方全部运营活动开展六体系全面审计，核查CGMP合规性，并评估CAPA的完成情况与有效性，之后贵方方可向FDA申请解决合规状态。

Your use of a consultant does not relieve your firm's obligation to comply with CGMP.

聘请顾问并不能免除贵公司遵守CGMP的法定义务。

Repeat Observations at Multiple Sites

多厂区重复出现同类缺陷

In a previous regulatory meeting held on January 15, 2025, FDA discussed similar CGMP violations at this facility. You proposed specific remediations for these violations in your response.

在2025年1月15日的监管会议中，FDA已就本厂区同类CGMP违规事项进行沟通，贵方当时提交了针对性整改方案。

FDA also cited similar CGMP violations at other facilities in your company's network. These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate.

FDA在贵集团其他厂区也发现同类CGMP违规。多厂区反复发生同类问题，证明管理层对药品生产的监督管控不足。

Your firm's executive management remains responsible for fully resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance. You should immediately and comprehensively assess your company's global manufacturing operations to ensure that systems, processes, and the products manufactured conform to FDA requirements.

贵公司高管层负有全部责任，彻底解决所有缺陷与系统性漏洞，持续满足CGMP合规。贵方应立刻全面评估集团全球生产运营，保证体系、工艺、产品符合FDA要求。

Drug Recall

药品召回

On July 17, 2026, FDA held a teleconference with your firm and recommended that you voluntarily recall one lot of cefazolin and various (b)(4) drugs currently in distribution from the U.S. market, to which you agreed.

2026年7月17日，FDA与贵公司召开电话会议，建议贵方主动召回正在美国市场流通的一批头孢唑林以及多款(b)(4)药品，贵方予以同意。

The company announcement for the cardboard particulate recall was posted to the FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/baxter-issues-voluntary-nationwide-recall-cefazolin-dextrose-injection-usp-2g-100ml-20mg-ml-single

纸板微粒相关召回公告已发布于FDA官网：FDA召回公告页面。

Request for a Meeting with FDA

申请与FDA召开会议

After you submit your response to this warning letter, we recommend that you reach out to this office to arrange for a teleconference to discuss your corrective actions and preventive actions in detail. Direct your request to Kathryn Hall at [email protected].

在贵方提交本警告函的答复后，建议贵方联系本办公室安排电话会议，详细讨论纠正与预防措施。请将会议申请发送至Kathryn Hall，邮箱：[email protected]。

Conclusion

结论

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

贵方有责任调查并确定所有违规事项的根本原因，实施纠正与预防措施，确保未来持续合规，避免本次及其他违规事项再次发生。

Unresolved violations may prevent other Federal agencies from awarding contracts. Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

未解决的违规事项可能导致其他联邦机构不予授予合同。未整改违规事项还可能导致FDA暂停签发出口证书。在所有违规事项完全整改、且FDA确认贵方符合CGMP之前，FDA可能暂停批准以贵公司为生产企业的新申请或补充申请。FDA可能开展再次检查，核实贵方已完成违规事项的整改。

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER's Drug Shortages Staff immediately, at [email protected], so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356c(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

若贵方正在考虑采取可能导致本厂区药品供应中断的措施，FDA要求贵方立即联系CDER药品短缺工作组（邮箱：[email protected]），以便FDA与贵方共同探讨最有效的方式，使生产运营依法合规。联系药品短缺工作组也有助于贵方履行《美国法典》第21编356c(b)条规定的药品停产或中断报告义务。这也便于FDA尽快评估可能需要采取何种措施（如有）以避免药品短缺，保护依赖贵方产品的患者健康。

Request for a Meeting with FDA

申请与 FDA 召开会议

After you submit your response to this warning letter, we recommend that you reach out to this office to arrange for a teleconference to discuss your corrective actions and preventive actions in detail. Direct your request to Kathryn Hall at

[email protected].在贵方提交本警告函的答复后，建议贵方联系本办公室安排电话会议，详细讨论纠正与预防措施。请将会议申请发送至 Kathryn Hall，邮箱：

[email protected]。