FDA警告信 | 扬州某企业数据造假与检验流于形式

FDA警告信

2025年3月25日，美国FDA公布了针对扬州某企业的警告信，指出其不符合现行药品生产质量管理规范（CGMP）的要求。此次检查于2024年9月23日至27日在中国江苏扬州进行，调查发现的违规行为涉及原材料检验、供应商管理、质量部门监督以及数据记录管理等多个关键环节。

据FDA信中披露，该企业未能对入场物料进行必要的鉴别、纯度、含量和质量的检验，尤其是未对高风险物料，如存在污染风险的物料，采取符合美国药典（USP）标准的鉴别与限度测试。这使得产品安全性存疑，因其曾引发全球范围内致命中毒事故。与此同时，质量部门未能有效履行监管职责，对活性成分含量、产品稳定性以及生产人员培训等方面的监督也存在严重疏漏，使得最终药品是否符合预定标准成为未知数。

更为严重的是，检查过程中发现实验室记录数据造假情况，原始记录与重写记录之间存在不一致，甚至出现使用修正液对纸质记录进行涂改的情况。这一系列问题严重影响了数据的真实性和完整性，也使得企业质量管理体系的有效性受到质疑。

FDA在信中明确要求该企业在短期内提交一系列整改措施，包括对高风险物料进行全面检验、实施严格的供应商资格确认程序、开展详细的风险评估和全面的CAPA计划，并对过去三年内运往美国市场的批次产品进行回顾性分析。信函还强调，若企业未能在规定时间内完成整改，产品可能继续面临进口警报和更严重的市场退出风险。

此次警告信不仅是对该企业内部管理漏洞的严正警告，更反映出在全球化供应链背景下，生产企业亟需重视质量管理和数据可靠性。

———————————

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou Sion Commodity Co., Ltd., FEI 3011346498, at No. 168 Longwang Road, Hangji Industrial Park, Yangzhou, Jiangsu, from September 23 to 27, 2024.

2024年9月23日至27日，美国食品药品监督管理局（FDA）检查了药品生产设施，Yangzhou Sion Commodity有限公司（FEI 3011346498），其地址为中国（略，见上）。

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).

本警告信总结了成品制剂现行药品生产质量管理规范（CGMP）法规的严重违规情况。请参阅联邦法规（CFR）第21篇第210和211部分（21CFR第210和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).

由于你们的生产、加工、包装或储存的方法、设施或控制措施不符合CGMP，因此根据FD＆C法案501(a)(2)(B)条、21 USC 351(a)(2)(B)的规定，你们的药品被认为是掺假。

We reviewed your October 18, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

我们详细审查了你们于2024年10月18日对我们的FDA 483表的回复，并确认已收到你们的后续函件。

CGMP Violations |CGMP违规行为

During our inspection, our investigators observed specific violations including, but not limited to, the following.

在检查过程中，我们的调查员发现的具体违规行为包括但不限于以下情况。

1

物料鉴别

1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

1.你们未能检验每种物料样品的鉴别以及是否符合所有适当的纯度、含量和质量的书面质量标准。你们也未能以适当的时间间隔验证和建立物料供应商检验分析的可靠性（21 CFR 211.84(d)(1)和211.84(d)(2)）。

You manufacture over-the-counter (OTC) drug products including(b)(4). Your firm failed to test incoming components used in manufacturing your finished OTC drug products to determine identity, purity, strength, and quality, and your firm did not establish a vendor qualification program for your raw material suppliers.

你们生产的非处方(OTC)药品包括(b)(4)。你们公司未能对生产你们OTC成品药品时使用的进场物料进行检验，以确定其鉴别、纯度、含量和质量，你们公司也未针对原材料供应商建立供应商资格确认计划。

Your firm used results from your suppliers’ certificates of analysis (COAs) without establishing the reliability of your suppliers’ analyses through appropriate validation and without conducting at least one specific identity test on each incoming lot of components. You may not rely on your suppliers’ COA to verify the identity of your components.

你们公司使用了供应商的分析证书(COA)中的结果，但未通过适当的验证确定供应商分析的可靠性，也未对每一批进场物料进行至少一个专属鉴别检验。你们不能依赖供应商的COA来确认物料鉴别。

In previous correspondence on September 28, 2023, associated with an FDA records request under section 704(a)(4) of the act, your firm committed to performing independent testing, to include identity testing for each shipment of high-risk component, as required by 21 CFR 211.84 (d)(1) & (2), using equivalent or better methods to those in the United States Pharmacopeia (USP).

此前，根据法案第704(a)(4)节FDA提出记录要求，你们在2023年9月28日与此相关的先前信函中，你们公司承诺将进行独立检验，包括对每批高风险物料进行鉴别检验，按照21 CFR 211.84 (d)(1)和(2)的要求，使用与美国药典标准相当或更优的方法。

However during the inspection, and contrary to previous commitments, your firm failed to demonstrate that you adequately tested each shipment of each lot of the incoming components at high-risk of(b)(4) contamination. These include, but are not limited to, testing of (b)(4) solution you used in manufacturing drug products to determine their appropriate identity. Identity testing for these and certain other high-risk drug components include a limit test in the USP to ensure that the component meets the relevant safety limits for levels of (b)(4). Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in manufacture of your drug products.

但在检查期间，与先前的承诺相反，你公司未能证明你对每一批入场的、存在(b)(4)污染高风险的物料进行了充分检验。这些检验包括但不限于，对你们在生产药品时使用的(b)(4)溶液进行检验以确定其适当鉴别。对这些和某些其他高风险药品物料鉴别检验包括USP中的限度检验，以确保该物料符合(b)(4)水平的相关安全限度。你们未使用可检验这些有害杂质的USP鉴别检验方法，对每一批每批货物进行鉴别检验，因此你们未能保证这些物料可用于生产你们的药品。

The use of ingredients contaminated with(b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4) to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for (b)(4) contamination at (b)(4).

使用受(b)(4)污染的物料已导致全球范围内发生多起致命中毒事件。请参阅FDA指导文件(b)(4)，帮助你们在(b)(4)生产含有高风险(b) (4)污染物料的药物时满足CGMP要求。

Additionally, you failed to perform identity testing on the component(b)(4) and lacked adequate impurities testing on (b)(4) before being used in manufacturing. Furthermore, (b)(4) was not adequately monitored for (b)(4).

此外，你们未对物料(b)(4)进行鉴别检验，在用于生产之前未对(b)(4)进行充分的杂质检验。此外，未对(b)(4)进行充分监控。

In your response on October 18, 2024, you indicate that you have updated your procedures to mandate the testing of identity and purity of active ingredients and the testing of identity of nonactive ingredients. Your response is inadequate because you did not address your plans for qualification of your component suppliers, did not address your previous commitments to perform identity testing on high-risk components, and failed to clarify whether your firm tested all lots of drug products that you distributed to the United States for risk of(b)(4). You also failed to adequately address quality attributes of your components.

在你们于2024年10月18日作出的回复中，你们表示已经更新了你们的程序，要求对活性成分的鉴别和纯度进行检验，并对非活性成分的鉴别进行检验。你们的回复是不充分的，因为你们没有说明对物料供应商进行资格确认的计划，没有说明你们之前对高风险物料进行鉴别检验的承诺，也没有说明你们公司是否对你们流通到美国的所有药品批次就(b)(4)风险进行了检验。你们也没有充分说明你们物料的质量属性。

In response to this letter, provide:

回复此函时，请提供：

A commitment to provide (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4).

承诺在自本函之日起30个日历日内，针对用于所有批次药品生产中高风险药物物料，提供(b)(4)检验结果。或者，如果没有某个物料批次的留样，则对所有可能受影响的成品制剂批次进行留样检验，以确定是否存在(b)(4)。

A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) contamination (including, but not limited to, (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective action and preventive action (CAPA) that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.

就含有任何有 (b)(4)污染风险的物料（包括但不限于(b)(4)）、且在效期内的药品，提供全面的风险评估。立即采取适当的措施，就任何可能含有(b)(4)的物料或相关药品批次，确定其安全性，包括通知客户和召回任何受污染批次的产品。确定其它适当的CAPA，以确保未来的供应链安全，包括但不限于：确保所有进场原料批次均来自有充分资质的生产商、且不含不安全的杂质。在你们对本函的回复中详细说明这些行动。

A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of (b)(4) and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.

说明如何检验每个批次，确定是否符合有关鉴别、含量、质量和纯度质量标准。如果你们打算接受供应商COA的结果，而不是检验每个物料批次的含量、质量和纯度，请说明如何进行初始验证和定期再验证，从而稳健地确定供应商结果的可靠性。此外，还应承诺：对于每个进场物料批次，至少进行一个专属鉴别检验。对于(b)(4)和某些其他高风险物料，我们注意到这包括美国药典(USP)专论A、B和C部分的性能表现。

The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.

你们用于检验每批高风险药品物料的化学质量控制标准，以确定其是否可接受用于生产。

A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.

对你们的物料系统进行全面、独立的审查，以确定所有物料、容器和密封件的供应商是否均有资质，并为物料指定了适当的有效期或复验日期。审查还应确定进场物料控制是否足以防止使用不合适的物料、容器和密封件。

A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your (b)(4) system consistently produces (b)(4) that meets (b)(4) USP monograph specifications and appropriate microbial limits.

一项程序，用于监管持续控制、维护和监测计划，以确保(b)(4)系统可以持续生产符合(b)(4) USP专论质量标准和适当微生物限度的(b)(4)。

2

质量部门未能履职

2. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

2.质量部门未能履行职责，以确保所生产的药品符合CGMP要求，并符合有关鉴别、含量、质量和纯度的既定质量标准(21 CFR 211.22)。

Your QU did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to:

你们的QU没有对你们药品的生产提供充分的监督。例如，你们的QU未能：

Perform assay testing for the strength of the active ingredient in (b)(4) drug products (21 CFR 211.165(b)).

对(b)(4)药品中活性成分的含量进行分析检验（21 CFR 211.165（b））。

Ensure an adequate stabilityprogram (including assessment of product potency over the shelf life) tosupport your claimed (b)(4) expiry for (b)(4) drug products (21 CFR 211.166).

确保有充分的稳定性计划（包括对效期内产品含量的评估），来支持你们声称的(b)(4)药品的(b)(4)有效期（21 CFR211.166）。

Ensure that personnel hadadequate training and experience for the production and analysis of (b)(4) drugproducts (21 CFR 211.25(a)).

确保人员接受过充分的培训，并具备(b)(4)药品生产和分析经验（21 CFR 211.25（a））。

Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished product specifications and are suitable for release to consumers.

对于确保你们生产的药品符合所有预定的质量属性，检验至关重要，这些属性适用于其预期用途。由于你们没有对每一批药品进行充分的检验，因此你们不知道它们是否符合所有适当的成品质量标准，是否适合向消费者发放。

You did not ensure that your QU implemented its basic functions. Your management should immediately and comprehensively assess your company’s manufacturing operations to ensure that your systems, processes, and products meet CGMP.

你们未能确保你们的质量部门履行其基本职能。你们的管理层应立即全面评估你们公司的生产运营，以确保你们的系统、流程和产品符合CGMP。

See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.

请参阅FDA的指南《药品CGMP法规质量体系方法》，以帮助实施质量体系和风险管理方法，满足CGMP法规21 CFR第210和211部分的要求，网址为(略，见上)。

In response to this letter, provide:

回复此函时，请提供：

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:

全面的评估和整改计划，以确保你们的质量部门获得有效运作的权限和资源。评估还应包括但不限于：

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

确定你们使用的程序是否可靠和适当。

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

在整个运营过程中质量部门进行监督的规定，以评估对相应规范的遵守情况。

A complete and final review of each batch and its related information before the QU disposition decision.

在质量部门决定处置之前，对每批产品及其相关信息进行完整和最终审查。

Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.

监督和批准调查以及履行所有其它质量部门职责，以确保所有产品的鉴别、含量、质量和纯度。

Performing a retrospective analysis of all batches shipped to the United States for the past 3 years to ensure product in U.S. commerce meets specifications for potency and purity. Your action plan to address any product quality or patient safety risks for batches of (b)(4) drug products in U.S. distribution, including potential customer notifications and recalls or market withdrawals.

对过去3年运往美国的所有批次进行回顾性分析，以确保美国商业批次产品符合含量和纯度质量标准。你们的行动计划，用于解决美国流通的(b)(4)药品批次的任何产品质量或患者安全风险，包括潜在客户通知和召回或市场撤回。

A copy of the quality agreement with the contract testing laboratories used for finished product testing. Indicate where in this agreement specifies potency testing and provide documentation supporting that potency testing occurs before release of your (b)(4) drug product.

与用于成品检验的合同检验实验室签订的质量协议副本。指出该协议中规定含量检验的地方，并提供文件，证明在放行你们的(b)(4)药品之前进行含量检验。

Justification for the potency discrepancy noted in your response pertaining to product retained testing. Your response demonstrated a (b)(4) potency specification (≤ (b)(4)%) for retained (b)(4) drug products as opposed to your label claim of (b)(4)% (b)(4).

就你们在回复中指出的与产品留样检验有关的含量差异，给出论证。你们的回复表明，留样的(b)(4)药品的(b)(4)含量质量标准(≤ (b)(4 ) %)与你们标签上声称的(b)(4)% (b)(4)不同。

3

数据可靠性

3.Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).

3.你们未能确保实验室记录包含所有检验的完整数据，以确保符合既定质量标准和标准(21 CFR 211.194(a))。

Your laboratory records lacked complete and original data to support the analyses performed. For example:

你们的实验室记录缺乏完整的原始数据，来支持所进行的分析。例如：

Your laboratory records included missing data. Furthermore, there were discrepancies between the original and re-written versions of testing records and COAs pertaining to active and non-active ingredients used in the manufacture of OTC drug products.

你们的实验室记录中缺少数据。此外，就OTC药品生产中使用的活性成分和非活性成分的检验记录和COA，在在原始和重写的版本之间，存在差异。

Your firm did not retain original data to support testing of components used to manufacture OTC drug products for the U.S. market. During our inspection, you confirmed that original data, including balance printout slips, (b)(4) times, (b)(4), sample preparations, and equipment logs were not maintained.

你们公司未保留原始数据，以支持对用于生产美国市场OTC药品的物料进行检验。在我们检查期间，你们确认未保留原始数据，包括天平打印单、(b)(4)时间、(b)(4)、样品制备和设备台账。

The use of correction fluid (white-out) was also observed to make corrections on paper records documenting microbial analyses of finished products and raw materials. These documentation practices raise concerns about the integrity, authenticity, and reliability of all your data, and quality of your drug products. Document control is essential to maintaining an adequate quality system.

我们还观察到，你们使用修正液（涂改液），对成品和原材料微生物分析的纸质记录进行修改。这些记录实践引起了对所有数据的完整性、真实性和可靠性以及药品质量的担忧。文件控制对于维持适当的质量体系至关重要。

In your response, you acknowledge that “QA management did not have a sound understanding of CGMP requirements.” You also commit to performing retrospective testing of “materials,” and state that you have updated procedures and re-trained personnel. Your response is inadequate, as you fail to fully consider comprehensive data integrity (DI) remediation to address the gaps and uncertainties caused by a significant adverse pattern of data that was discarded, lost, or not recorded contemporaneously. Additionally, your response did not consider plans to assess your manufacturing operation’s documentation system to determine where they are insufficient.

在你们的回复中，你们承认“QA管理层对CGMP要求没有充分理解”。你们还承诺对“物料”进行回顾性检验，并表示你们已经更新了程序、并重新培训了人员。你们的回复是不充分的，因为你们没有充分考虑全面的数据可靠性(DI)补救措施，来解决由丢弃、丢失或未同步记录的严重不利数据模式造成的差距和不确定性。此外，你们的回复没有考虑评估你们生产操作的文档系统，以确定其不足之处的计划。

Reliability of data is fundamentally compromised when there is a failure to record or maintain complete and accurate records of test results, or conditions associated with all tests. Furthermore, the lack of reliable data compromises the quality unit’s (QU) ability to exercise its function of ensuring compliance to applicable standards.

如果未能记录或保留完整准确的检验结果或与所有检验相关的条件，数据可靠性就会从根本上受到损害。此外，缺乏可靠的数据会损害质量部门(QU)履行确保符合适用标准的职能的能力。

4

数据可靠性修复

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance documentData Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant DI practices at https://www.fda.gov/media/119267/download.

你们的质量体系无法充分确保数据的准确性和可靠性，以支持你们生产的药品的安全性、有效性和质量。有关如何建立和遵循CGMP数据可靠性合规性实践的指南，请参阅FDA的指南《数据可靠性和药品CGMP合规性》，网址(略，见上)。

We acknowledge that you are using an independent third-party consultant to perform DI training. However, we strongly recommend that you retain an independent third-party qualified consultant to audit your operation and assist in your DI remediation to meet FDA requirements. In response to this letter, provide:

我们确认你们正在使用独立的第三方顾问进行数据可靠性培训。但是，我们强烈建议你们聘请独立的第三方有资质顾问来审核你们的运营，并协助你们进行数据可靠性补救，以满足FDA要求。

In response to this letter, provide:

回复此函时，请提供：

1、A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include：

对数据记录和报告中不准确的程度进行全面调查。你们的调查应包括：

A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.

详细的调查方案和方法；涵盖所有实验室、生产活动和系统的评估汇总；以及就拟议排除的运营部分，提供论证。

Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.

对现任和此前员工进行访谈，以确定数据不准确的性质、范围和根本原因。我们建议这些面谈由有资质的第三方进行。

An assessment of the extent of DI deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered DI lapses.

对你们设施中数据可靠性缺陷程度的评估。识别遗漏、更改、删除、记录销毁、非同步完成记录和其它缺陷。就你们发现数据可靠性缺陷，描述设施运营的所有方面。

A comprehensive retrospective evaluation of the nature of the testing DI deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all DI lapses.

对检验数据可靠性缺陷的性质进行全面回顾性评估。我们建议，由第三方评估所有数据可靠性缺陷，该第三方在识别出潜在违规的领域拥有特定的专业知识和资质。

2、A current risk assessment of the potential effects of the observed failures on the quality of your drugs.Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of DI and analyses of the risks posed by ongoing operations.

当前风险评估，评估观察到的失效对你们所检验药品质量的潜在影响。你们的评估应包括对因数据可靠性不合格而影响药品放行的患者风险的分析，以及对正在进行的运营带来的风险的分析。

3、A management strategy for your firm that includes the details of your global CAPA plan. Your strategy should include:

你们的管理策略，包括整体纠正和预防措施(CAPA)计划的详细信息。你们的策略应包括：

A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.

详细的纠正措施计划，描述你们打算如何确保你们生成的所有数据（包括分析数据、生产记录和提交给FDA的所有数据）的可靠性和完整性。

A comprehensive description of the root causes of your DI lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for DI lapses remain able to influence CGMP-related or drug application data at your firm.

全面描述数据可靠性缺陷的根本原因，就当前行动计划的范围和深度是否与调查和风险评估结果相称，提供证据。就数据完整性缺陷的负责人，说明其是否仍能影响CGMP或药物申请相关的数据。

Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.

临时措施，涉及你们已采取或将要采取的措施、以保护患者和确保药品质量，例如通知客户、进行额外检验、在稳定性计划中添加批次以确保稳定性、药品申请相关措施和加强投诉监控。

Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.

长期措施，描述所有整改和改进措施，涉及程序、工艺、方法、控制、系统、管理监督和人力资源（例如培训、人员配备改进），以确保数据可靠性。

A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your DI remediation protocol.

承诺在你们执行数据可靠性整改方案后，至少两年内让有资质的顾问进行深入的年度审计，以协助评估CAPA的有效性。

Inform FDA if you will be assigning DI oversight responsibility to an individual who is fully empowered to receive anonymous complaints from employees reporting DI concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).

如果你们计划指派某人负责数据可靠性监督，请告知FDA。该负责人应完全有权接收员工匿名举报的数据可靠性问题；此外，其还应具备确保任何潜在违规情况能够迅速接受调查的权限。调查应由独立的质量保证部门进行，并在必要时引入外部专家协助。

A status report for any of the above activities already underway or completed.

正在进行或完成的上述所有活动的状态报告。

5

结论

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

本函中提到的并非是你们设施中存在的违规情况的完整清单。你们有责任调查和确定所有违规情况的原因，并防止其再次发生或发生其它违规行为。

FDA placed products offered for import into the United States from your firm on Import Alert 66-40 on January 31, 2025.

2025年1月31日，FDA将你们公司拟进口到美国的产品列入进口警报66-40。

Correct any violations promptly. 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 any violations.

及时纠正所有违规情况。FDA可能会暂停批准将你们列为新药申请或补充申请的药品生产商，直到所有违规情况得到彻底解决、且我们知晓，你们遵守了法案。我们可能会再次检查，以确认你们是否已针对所有违规情况采取了纠正措施。

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Yangzhou Sion Commodity Co., Ltd., No. 168 Longwang Road, Hangji Industrial Park, Yangzhou, Jiangsu 225111, China, 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 [or misbranded] 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).

未能解决所有违规情况，这还可能导致FDA依据FD&C法案第801条（21 USC 381）继续拒绝你们生产的产品入境美国。根据该法规，视为掺假或标识错误的产品将被扣留或拒绝入境，因为其生产使用的方法与控制不符合CGMP，CGMP是在FD＆C法案(501)(a)(2)(B)条、21USC351(a)(2)(B)条中被要求的。

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 days. Specify what you have done to address any violations 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.

本信函通知你们我们的发现，并为你们提供解决上述缺陷的机会。收到本信函后，请在15个工作日内以书面形式回复本办公室。说明你们为解决所有偏差并防止其再次发生所做的工作。在回复本信函时，你们可以提供更多信息供我们考虑，因为我们将继续评估你们的活动和实践。如果你们无法在15个工作日内完成纠正措施，请说明延误原因和完成时间表。