人福医药子公司收FDA警告信，葛店人福或面临出口禁令风险

来源：市场资讯

项乾消息：近日，美国食品药品监督管理局（FDA）向人福医药（600079.SH）旗下核心原料药子公司——湖北葛店人福药业有限责任公司发出警告信，直指该公司在原料药（API）生产过程中存在两大缺陷。

警告信内容指出，FDA检查人员于2025年11月3日至7日对葛店人福位于湖北省鄂州市葛店经济开发区的生产基地进行了现场检查，发现该公司用于生产出口美国市场的原料药设备存在严重问题。检查人员观察到，多个API直接接触设备内壁出现大量划痕和不明污渍，设备盖子和边缘存在明显标记痕迹。

葛店人福在2025年11月28日的回复中表示，设备接触面材质与化学工艺（特别是特定溶剂和反应过程）之间存在"不兼容性"。工艺中使用的特定化学品会削弱设备内壁涂层，导致涂层脱落、变色及划痕。FDA明确指出，这些问题表明设备接触面完整性已受损，可能导致API受到颗粒物污染，或因化学浸出反应改变药品质量。

对此，FDA认定葛店人福的回复"不充分"，理由包括：未提供基于工艺化学的科学依据来支撑预防性维护频次；未评估整条设备生产线所有内壁与工艺的反应性；仅以检测结果合格为由，主观认定对产品质量风险较低。

FDA警告信还指出，葛店人福的质量部门（QU）未能履行其基本监管职责。具体表现为：未确保生产设施得到适当维护（如门窗周围存在缝隙）；未评估设备接触面材质与化学工艺的兼容性，以确保其适用于预期用途。

尽管葛店人福在回复中称已修订质量部门职责，增加现场抽查频率，但FDA认为其修订后的检查清单仅要求判断设备是否"处于正常工作状态"，表述过于模糊，无法有效识别变色、划痕、标记及生产区域结构问题。

FDA在警告信中指出："贵公司未按照CGMP要求运行有效的质量体系"，并明确要求公司高管层立即对全球生产运营进行全面评估。

警告信明确警告，若葛店人福未能及时纠正偏差，FDA可能依据《联邦食品、药品和化妆品法》第801(a)(3)条，拒绝该公司产品进入美国市场。这意味着葛店人福生产的原料药在美国海关可能面临扣留或拒绝入境。

葛店人福作为人福医药重要的原料药出口基地，其产品主要销往美国等规范市场。

此外，FDA在警告信中明确表示，"在偏差完全解决并确认符合CGMP之前，FDA可能拒绝批准将贵公司列为药品生产厂商的新申请或补充申请"。

FDA在警告信中要求葛店人福提交多项整改方案，包括：设备材质全面更换、批次回顾性审查、质量体系重建等。

根据FDA要求，葛店人福须在收到警告信后15个工作日内提交书面回复，详细说明已采取的纠正措施及预防再发的方案。若无法在期限内完成整改，需说明延迟原因及完成时间表。

值得注意的是，FDA在警告信末尾提及，根据仿制药用户付费法案（GDUFA）III承诺函，葛店人福可能有资格申请"警告信后会议"（Post-Warning Letter Meeting），以获得FDA对整改计划充分性和完整性的初步反馈。这为公司提供了与监管机构沟通的渠道，但能否有效利用仍取决于整改方案的质量。

人福医药集团成立于1993年，1997年在上海证券交易所上市，是国内麻醉镇痛药品领域的龙头企业。公司业务涵盖医药工业、医药商业及国际化业务，旗下拥有葛店人福、武汉人福、宜昌人福等多家核心子公司。

葛店人福作为集团重要的原料药生产基地，专注于甾体激素类、麻醉镇痛类等特色原料药的生产，产品出口欧美等市场。

警告信全文：

Warning Letter 320-26-93

June 3, 2026

Dear Dr. Chen:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Hubei Gedian Humanwell Pharmaceutical Co., Ltd., FEI 3004117486, located at No. 25 Juxian Road, Gedian Economic Development District, Ezhou City, Hubei Province, China, from November 3 to 7, 2025.

This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs 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).

We reviewed your November 28, 2025 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigator observed specific deviations including, but not limited to, the following.

1. Failure to clean equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the API beyond the official or other established specifications.

Your firm manufactures (b)(4) for the U.S. market. During the inspection, our investigator observed numerous scratches and (b)(4) stains on the interior API-contact surfaces of your (b)(4) vessels, as well as (b)(4) markings on the lid and rim of the (b)(4) of your (b)(4) vessel. These markings and discolored stains indicate that the integrity of the API-contact surfaces is being compromised which can lead to contamination of your API with particulate matter (e.g., (b)(4) particles) or alter the quality of the API via chemical leachable reactions.

In your response, you state that compatibility between the equipment product contact surface material of construction and the chemical process, specifically the (b)(4) and the (b)(4) process, is insufficient. You state that the (b)(4) chemicals used in the process weakens the (b)(4) on the (b)(4) surfaces which leads to (b)(4) manifested as (b)(4) stains/discoloration and scratches. You (b)(4) your (b)(4) and (b)(4) the interior walls and plan to perform preventive (b)(4) maintenance (b)(4). You (b)(4) the (b)(4) markings on the (b)(4) and lid and replaced the (b)(4) gasket sealing the (b)(4) lid.

Your response is inadequate because you do not support the frequency of your preventive (b)(4) maintenance schedule with scientific rationale based on your processes’ chemistry. Your response also did not evaluate the reactivity of all interior surfaces of the equipment train with your (b)(4) process. Furthermore, you rationalized that the risk to product quality risk is low based on results of release testing using a qualified method.

Your equipment materials of construction are inadequate because your product-contact surfaces may alter the quality of the product in that they were additive, absorptive, or reactive. Inadequately maintained manufacturing equipment can lead to potential contamination that could compromise the quality and safety of your APIs.

In response to this letter, provide:

• Your corrective action and preventive action (CAPA) plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.

• A retrospective, independent review of all batches within expiry that could have been affected by scratches and discoloration within the (b)(4) vessels introduced as a result of your manufacturing process, including an evaluation of retain samples for elements within your (b)(4) and/or impurities. Include a review of customer complaints for the last three years.

• A review of all your manufacturing processes to determine whether there is reactivity with all respective product-contact surfaces in your equipment.

• An evaluation of your process and equipment to determine whether changes will be implemented to remove the risk of foreign material introduced to APIs due to process design and inadequate product contact materials of construction. Include a list of all product contact surfaces exposed to varying chemical reactions in your facility, and supporting information regarding (b)(4) resistance against typical conditions in the vessels. Also include a plan, including timeline, for changing product contact surfaces to appropriate (b)(4) materials of construction given the inherent nature of the chemical processes utilized.

2. Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP.

Your quality unit (QU) was not exercising its basic responsibilities for oversight of the manufacture of your APIs. For example, your QU failed to ensure the following:

• Buildings and facilities used in the manufacture of APIs have been properly maintained (e.g., no gaps around windows and doors).

• You did not evaluate the compatibility between the equipment product contact surface material of construction and the chemical processes used in the manufacture of APIs to ensure suitability for its intended use.

In your response, you state that you revised the job responsibilities of the QU to increase the spot check frequency and to inspect the production floor equipment conditions. Your response is inadequate because the revised QU inspection duties checklist includes determining whether the equipment is “under normal working conditions.” This statement is vague and does not specify or provide appropriate guidance to identify discoloration, scratches, markings, and production room structural issues.

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

In response to this letter, provide:

• An assessment of each drug product process to ensure suitability of equipment for its intended use and sufficiency of detectability in your monitoring and testing systems.

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

  o A determination of whether procedures used by your firm are robust and appropriate

  o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices

API CGMP Guidance

FDA considers the expectations outlined in International Conference on Harmonization (ICH) Q7 when determining whether APIs and intermediates are manufactured in conformance with CGMP. See FDA’s guidance document Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients for guidance regarding CGMP for the manufacture of APIs at https://www.fda.gov/media/71518/download.

Conclusion

The deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.

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 drugshortages@fda.hhs.gov, 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.

Correct any deviations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any deviations.

Failure to address any deviations may also result in the FDA refusing admission of articles manufactured at Hubei Gedian Humanwell Pharmaceutical Co., Ltd., FEI 3004117486, located at No. 25 Juxian Road, Gedian Economic Development District, Ezhou City, Hubei Province, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any deviations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3004117486 and ATTN: Barbara Wilimczyk-Macri.

Sincerely,

/S/

Francis Godwin

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research

Cc: Registered U.S. Agent

Registrar Corp