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).
本警告信概述了公司在成品药品生产中严重违反现行良好生产规范（CGMP）法规的情况。请参阅《联邦法规》第 21 篇第 210 部分和第 211 部分。
During our inspection, our investigators observed specific violations including, but not limited to, the following.
在检查期间，检查员观察到了特定的违规行为，包括但不限于以下内容。
1.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).
公司未能对任何批次或其任何成分未达到规格要求的不明差异或不合格情况进行彻底调查，无论该批次是否已分销（21 CFR 211.192）。
You manufacture over-the-counter (OTC) drug products, including (b)(4) medications. You failed to thoroughly investigate several out-of-specification (OOS) laboratory results from October 2024 to June 2025 and lacked corrective action and preventive action (CAPA). For example, (b)(4) tablets, lot (b)(4), and (b)(4) tablets, lot (b)(4), failed assay testing at the 9-month stability timepoint. Your retest using additional samples also produced failing results. Your laboratory investigations did not include sufficient details and lacked root causes for the failures. Furthermore, you did not notify your customers about the failing stability results for the distributed lots.
公司生产非处方 (OTC) 药品，包括(b)(4)药品。从2024年10月至2025年6月期间，未能对多个超出标准 (OOS) 的实验室检测结果进行彻底调查，并且缺乏纠正与预防措施 (CAPA)。例如，(b)(4)片剂，批次(b)(4)，和(b)(4)片剂，批次(b)(4)，在9个月的稳定性测试时间点上含量测定结果不合格。使用额外样品进行的复测也未通过。贵公司的实验室调查未包含充分的细节，也没有找出不合格的根本原因分析。此外，公司未将这些已分销批次的不合格稳定性结果告知客户。
In your response, you state that while the above investigations did not identify root causes, the OOS results are “representative of microscopic packaging defects” noted in a previous investigation and “are not formula stability related.” You acknowledge that you did not take market action for the failing batches, despite noting the possibility that the defects may impact drug product effectiveness.
贵司在回复中声明，虽然上述调查未确定根本原因，但OOS结果，是之前调查中提到的“微小包装缺陷”，并且“与配方稳定性无关”。公司尽管注意到缺陷可能会影响药品有效性，但并未对不合格批次采取市场行动。
Your response is inadequate because your investigation lacked sufficient rigor to show how your “packaging defects” led to a failure in product quality. Additionally, you failed to initiate a CAPA at the conclusion of the investigations. This was a repeat observation from FDA's 2021 inspection where you attributed the root cause of assay failures to packaging defects without providing supporting evidence of how these defects impact your analytical methodology and failed to implement appropriate CAPA.
公司的回复不充分，因为调查缺乏足够的严谨性，无法说明“包装缺陷”是如何导致产品质量不合格的。此外，公司在调查结束时未能启动CAPA。这是FDA在2021年检查中观察到的重复项，当时将含量测定失败的根本原因归咎于包装缺陷，但未提供这些缺陷如何影响分析方法的支持证据，并且未能实施适当的CAPA。
Inadequate investigations can lead to unidentified root causes, ineffective CAPA, and recurring problems that compromise the ability to manufacture safe and effective drug products.
调查不充分可能导致无法识别根本原因、CAPA无效以及问题反复出现，从而影响生产安全有效药品的能力。
2.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)).
公司未能建立实验室控制措施，其中包括科学合理且适当的可接受标准、对照品、取样方案和检验方法，以确保原料、药品包装容器、密封件、中间产品、标签及制剂符合相应的鉴别、规格、质量和纯度标准（21 CFR 211.160(b)）。
You failed to demonstrate that your sample preparation methods are suitable for testing drugs or to account for how these methods could affect test results. For example, you use (b)(4) to prepare samples of your (b)(4) tablets and (b)(4) tablets for high-performance liquid chromatography analysis. However, (b)(4), which can lead to inaccurate results showing OOS levels for (b)(4) content.
公司未能证明样品的制备方法适用于药品检测，未能解释这些方法如何影响检测结果。例如，使用(b)(4)来制备(b)(4)片剂和(b)(4)片剂的样品以用于高效液相色谱分析。然而，(b)(4)，这可能导致显示(b)(4)含量的检测结果不准确，显示为不合格水平。
In your response, you acknowledge that you did not fully meet the test method validation requirements, and that you will review and re-validate (b)(4) of your test methods assaying for (b)(4) in (b)(4) of your formulations. You commit to updating your analytical method validation master plan to incorporate all current test method validation requirements. You also commit to reviewing all other test methods used to assay your other OTC drug products.
在回复中，公司承认未完全满足检测方法验证的要求，并将审查和重新验证(b)(4)种用于测定(b)(4)种配方中(b)(4)含量的检测方法。公司承诺更新分析方法验证主计划，以纳入所有当前的检测方法验证要求。公司还承诺审查用于测定其他OTC药品的所有其他检测方法。
Your response is inadequate in that it did not fully evaluate the scope of this deficiency and the impact to product quality. You did not commit to a retrospective review and risk assessment for all test results generated using these methods. Additionally, you have not established interim controls to use during the review and validation of your test methods.
公司的回复不够充分，因为没有全面评估此缺陷的范围及其对产品质量的影响。公司也未承诺对使用这些方法产生的所有检测结果进行回顾性审查和风险评估。此外，公司未建立用于检测方法审查和验证期间的临时控制措施。
备注：(b)(4)为被检查企业的产品信息或其他敏感信息。
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