Warning Letter 320-26-54
[中譯] 警告信 320-26-54

March 18, 2026
[中譯] 2026年3月18日

Dear Mr. Gao: The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou H&R Plastic Daily Chemical Co., Ltd., FEI 3014543859, at 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, from October 21 to 24, 2025.
[中譯] 高先生您好：美國食品藥物管理局（FDA）於2025年10月21日至24日查核了您的藥品製造廠（揚州H&R塑膠日化有限公司，FEI 3014543859，位於江蘇省揚州市廣陵區杭集鎮星園路188號）。

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). 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).
[中譯] 本警告信總結了製劑藥品在現行優良製造規範（CGMP）法規上的重大違規事項。請參閱聯邦法規第21篇（CFR）第210與211部分。由於貴公司在製造、加工、包裝或儲存的各種方法、設施或管制措施不符合CGMP，依據聯邦食品、藥品和化妝品法案（FD&C Act）第501(a)(2)(B)條（21 U.S.C. 351(a)(2)(B)），您的藥品被視為劣藥（adulterated）。

We have not received a response from your firm stating your actions to address the deficiencies identified during the inspection and cited on our Form FDA 483. We note that you continue to ship drug products to the United States. During our inspection, our investigator observed specific violations including, but not limited to, the following.
[中譯] 我們尚未收到貴公司針對查廠期間發現並列於FDA 483表上的缺失提出改善行動回覆。我們注意到您仍持續將藥品運往美國。在查核期間，我們的查核員觀察到了具體的違規事項，包含但不限於以下內容。

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
[中譯] 1. 貴公司未能針對每一批次的藥品，在放行前透過適當的實驗室檢驗來判定其是否符合最終規格，其中包含每項主成分的鑑別與含量（21 CFR 211.165(a)）。

Your firm contract manufactures an over-the-counter (b)(4) drug product. You failed to adequately test batches of your finished drug product for the identity and strength of your active ingredient (e.g. (b)(4)) before release and distribution. Your specification procedures only discuss appearance, color, and weight checks prior to batch release. Full release testing, which includes strength and identity testing of the active ingredient, must be performed before drug product batch release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that drug product batches conform to appropriate specifications before release.
[中譯] 貴公司代工製造一款非處方（b)(4)藥品。您未能在放行與運銷前，對成品批次的主成分（例如(b)(4)）的鑑別與含量進行充分檢驗。您的規格程序僅探討批次放行前的外觀、顏色及重量檢查。在藥品批次放行與運銷前，必須執行包含主成分含量與鑑別試驗的完整放行檢驗。若無適當檢驗，您即缺乏充分的科學證據來確保藥品批次在放行前符合適當規格。

In response to this letter, provide:
[中譯] 作為對本信函的回覆，請提供：

• A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies.
  [中譯] 一份針對貴公司實驗室實務、程序、方法、設備、文件化及分析員能力之全面且獨立的評估。
• Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
  [中譯] 基於此審查結果，提供一份詳細計畫以改善並評估您實驗室系統的有效性。
• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
  [中譯] 一份化學與微生物規格清單（包含檢驗方法），用於在批次處置決定前分析您各批藥品。
• An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  [中譯] 一份行動計畫與時間表，針對截至本信函日期仍在有效期限內且已運銷至美國的所有藥品批次，執行留樣的完整化學與微生物檢驗，以判定其品質。
• A summary of all results obtained from testing retain samples from each batch.
  [中譯] 每一批次留樣檢驗結果的總結報告。

If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
[中譯] 若此類檢驗顯示藥品品質不合格，請採取快速的矯正措施，例如通知客戶與啟動產品回收。

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. 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)).
[中譯] 2. 貴公司未能執行至少一項檢驗來確認藥品中各項組成原料的鑑別。貴公司亦未能在適當的週期內進行確效並建立供應商檢驗分析的可靠性（21 CFR 211.84(d)(1) 與 211.84(d)(2)）。

Your firm failed to conduct adequate identity testing on incoming components, including active pharmaceutical ingredients, used in the manufacturing of your drug products. Additionally, you relied on your suppliers’ certificates of analyses (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals. Without adequate testing and confirmation of reliability of supplier test results, you lack scientific evidence that the components conform to appropriate specifications prior to use in the drugs products you manufacture.
[中譯] 貴公司未能對用於製造藥品的進料原物料（包含原料藥 API）執行充分的鑑別試驗。此外，您依賴供應商的檢驗分析證明（COA），卻未在適當週期建立各供應商分析結果的可靠性。若缺乏適當檢驗與供應商檢驗結果可靠性的確認，您即缺乏科學證據證明原物料在用於製造藥品前符合適當規格。

In response to this letter, provide:
[中譯] 作為對本信函的回覆，請提供：

• A comprehensive, independent review of your material system, including but not limited to: evaluating all suppliers of materials (components, containers, and closures) to determine if they are reliable and appropriately qualified; an assessment of all materials to determine whether they are consistently of acceptable quality; a review to ensure assigned expiration or retest dates are appropriate (supported by data); adequacy of the supplier qualification program, and its selection, qualification, and disqualification provisions.
  [中譯] 一份針對貴公司物料系統全面且獨立的審查，包含但不限於：評估所有物料（原料、容器與封裝材）供應商以決定其是否可靠且具備適當資格；評估所有物料以決定其是否具備一致的可接受品質；審查以確保指定的有效期限或複驗日期是適當的（需有數據支持）；供應商資格認證計畫的充分性，及其選擇、資格確認與取消資格的規定。
• Based on a thorough review, provide a summary of your systems corrective actions and preventive actions to remediate the vendor qualification program and prevent use of unsuitable components, containers and closures.
  [中譯] 基於徹底的審查，提供一份貴公司系統矯正與預防措施（CAPA）總結，以改善供應商資格認證計畫並防止使用不合適的原料、容器與封裝材。
• The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.
  [中譯] 您用於檢驗並放行每一批次進料原物料以供製造使用的化學與微生物品質管制規格。
• A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity.
  [中譯] 描述您將如何檢驗每一原物料批次，以使其符合所有適當的鑑別、含量、品質與純度規格。
• 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 re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
  [中譯] 如果您打算接受供應商COA上的任何結果，而不是親自檢驗每一原物料批次的含量、品質與純度，請具體說明您將如何透過初始確效以及定期的再確效，穩健地建立供應商結果的可靠性。此外，請包含一項承諾，保證永遠對每一進料批次執行至少一項特定的鑑別試驗。
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.
  [中譯] 一份透過檢驗所有原物料以評估各製造商COA可靠性的結果總結。請附上描述此COA確效計畫的標準作業程序（SOP）。
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
  [中譯] 一份關於您用來確認並監督測試您所製造藥品之外包合約設施的計畫總結。

3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
[中譯] 3. 貴公司未能針對生產與製程管制建立充分的書面程序，以確保您所製造的藥品具備其所宣稱或聲稱的鑑別、含量、品質與純度（21 CFR 211.100(a)）。

Your firm failed to adequately qualify the equipment and validate the processes used to manufacture your (b)(4) drug product. You have not performed process performance qualification (PPQ) studies, nor do you have a meaningful ongoing program for monitoring process control, to ensure stable manufacturing operations and consistent drug quality. Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately to ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality are necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.
[中譯] 貴公司未能針對用於製造您(b)(4)藥品的設備進行適當的確認（Qualification）與製程確效。您尚未執行製程效能確認（PPQ）研究，亦缺乏實質有意義的持續性製程管制監控計畫，以確保穩定的製造操作與一致的藥品品質。製程確效旨在評估製程在整個生命週期中設計的健全性與管制狀態。製造製程的每個關鍵階段都必須有適當的設計，以確保原料投入、半成品及成品的品質。製程確認研究可判定是否已建立初始的管制狀態。在商業運銷前，必須完成成功的製程確認研究。此後，必須對製程效能與產品品質進行持續且嚴密的監督，以確保您在整個產品生命週期中維持穩定的製造營運。

See FDA’s guidance document for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.
[中譯] 請參閱 FDA 指引文件，以了解 FDA 認為適當的製程確效要素的一般原則與方法，網址：https://www.fda.gov/media/71021/download。

In response to this letter, provide:
[中譯] 作為對本信函的回覆，請提供：

• A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures.
  [中譯] 一份確保在整個產品生命週期維持管制狀態之確效計畫的詳細總結，以及相關程序。
• Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.
  [中譯] 描述您用於製程效能確認的計畫，以及對批次內與批次間變異的持續監控，以確保持續的管制狀態。
• A timeline for performing appropriate PPQ for each of your marketed drug products.
  [中譯] 為您每一款上市藥品執行適當 PPQ 的時間表。
• Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.
  [中譯] 同時提供風險評估，以及針對未執行任何製程確效研究即生產並運銷的藥品將採取之任何後續行動。
• Process performance protocol(s), and written procedures for qualification of equipment and facilities.
  [中譯] 製程效能計畫書，以及設備與廠房確認的書面程序。
• A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.
  [中譯] 一份用於設計、確效、維護、管制並監控您每一項製造製程的詳細計畫，該計畫應包含對批次內與批次間變異的嚴密監控，以確保持續的管制狀態。同時，請附上您設備與廠房的確認計畫。

4. 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).
[中譯] 4. 貴公司的品質管制單位未能履行其職責，以確保所製造的藥品符合CGMP，並滿足已建立的鑑別、含量、品質與純度規格（21 CFR 211.22）。

Your firm failed to establish an adequate quality unit (QU) with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure: Adherence to an adequate stability program (21 CFR 211.166(a)); Consistent and complete batch records (21 CFR 211.188); Appropriate examination of labeling and packaging materials for correctness, including but not limited to sufficiently accounting for all ingredients used in manufacturing, prior to packaging operations (21 CFR 211.130(d)).
[中譯] 貴公司未能建立一個具備監督藥品製造之職責與權力的適當品質單位（QU）。舉例來說，您未能確保：遵守適當的安定性試驗計畫（21 CFR 211.166(a)）；具備一致且完整的批次紀錄（21 CFR 211.188）；在包裝作業前，對標籤與包裝材料的正確性進行適當檢查，包含但不限於充分清點製造中所使用的所有物料（21 CFR 211.130(d)）。

There was a fundamental failure of production management to effectively oversee the procedures, practices, and suitability of the manufacturing operations. In addition, even when a QU consists of one or only a few, those persons are still accountable for overseeing ongoing effectiveness of all systems and procedures, and review of the results of manufacture to ensure state of control and adherence to all quality standards.
[中譯] 生產管理階層在有效監督製造作業的程序、實務操作與適宜性方面，存在根本性的缺失。此外，即使品質單位（QU）僅由一人或少數幾人組成，這些人員仍需負責監督所有系統與程序的持續有效性，並審查製造結果以確保管制狀態與符合所有品質標準。

In response to this letter, provide:
[中譯] 作為對本信函的回覆，請提供：

• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function.
  [中譯] 一份全面評估與改善計畫，以確保您的品質單位被賦予有效運作所需的權力與資源。
• The assessment should also include, but not be limited to: A determination of whether procedures used by your firm are robust and appropriate; Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices; A complete and final review of each batch and its related information before the QU disposition decision; Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.
  [中譯] 該評估亦應包含但不限於：判定貴公司所用程序是否穩健且適當；在整個營運過程中品質單位的監督條款，以評估是否遵守適當的實務操作；在品質單位做出處置決定前，對每一批次及其相關資訊進行完整且最終的審查；對各項調查的監督與核准，以及履行品質單位所有其他職責，以確保所有產品的鑑別、含量、品質與純度。

Quality Systems
[中譯] 品質系統

Your firm’s quality systems are inadequate. See FDA’s guidance document ICH Q10 Pharmaceutical Quality System, as well as Quality 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/71553/download and https://www.fda.gov/media/71023/download, respectively.
[中譯] 貴公司的品質系統並不充分。請參閱FDA指引文件「ICH Q10 製藥品質系統」，以及「製藥CGMP法規的品質系統方法」，以協助實施品質系統與風險管理方法，從而符合CGMP法規21 CFR第210與211部分的規定，網址分別為 https://www.fda.gov/media/71553/download 與 https://www.fda.gov/media/71023/download。

CGMP Consultant Recommended
[中譯] 建議聘請 CGMP 顧問

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 if your firm intends to resume manufacturing drugs for the U.S. market. 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. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
[中譯] 基於我們在貴公司發現的違規性質，若貴公司有意恢復為美國市場製造藥品，您應依據21 CFR 211.34的規定，聘請具備資格的顧問來評估您的營運，並協助貴公司符合CGMP要求。該合格顧問亦應對您整體的營運進行全面的六大系統（six-system audit）CGMP合規性稽核，並在您尋求解決與FDA合規狀態的問題之前，評估您矯正與預防措施（CAPA）的完成度與有效性。您使用顧問服務並不能免除貴公司遵守CGMP的義務。貴公司的高階管理層仍需負責解決所有缺失與系統性缺陷，以確保持續的CGMP合規性。

Conclusion
[中譯] 結論

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.
[中譯] 本信函中所引述的違規事項，並非旨在成為存在於貴廠的所有違規事項的完整清單。您有責任調查並確定任何違規事項的根本原因，並防止其再次發生或發生其他違規事項。

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on February 13, 2026. 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.
[中譯] FDA已於2026年2月13日將貴公司欲出口至美國的所有藥物與藥品列入進口警報 66-40（Import Alert 66-40）。請迅速改正任何違規事項。在所有違規事項完全解決且我們確認您符合CGMP之前，FDA可能會拒絕核准將貴公司列為藥品製造商的新藥申請或補充申請。我們可能會進行重新查廠，以確認您已完成針對任何違規事項的矯正措施。

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, 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).
[中譯] 未能解決任何違規事項，亦可能導致FDA依據FD&C法案第801(a)(3)條（21 U.S.C. 381(a)(3)），持續拒絕在江蘇省揚州市廣陵區杭集鎮星園路188號製造的物品進入美國。依據此權限，若物品看起來有劣藥嫌疑，其製造方法與管制措施似乎不符合FD&C法案第501(a)(2)(B)條（21 U.S.C. 351(a)(2)(B)）所定義的CGMP，則可予以扣留或拒絕進口。

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.
[中譯] 本信函通知您我們的發現，並提供您解決上述缺失的機會。在您收到本信函後，請於15個工作日內以書面形式回覆本辦公室。請具體說明您已採取了哪些措施來解決任何違規事項並防止其再次發生。作為對本信函的回覆，您可以提供額外資訊供我們在持續評估您的活動與實務操作時納入考量。若您無法在15個工作日內完成矯正措施，請說明延遲的原因與完成的時程表。

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3014543859 and ATTN: Philip Kreiter.
[中譯] 請將您的電子回覆寄至：CDER-OC-OMQ-Communications@fda.hhs.gov。請在您的回覆中註明FEI 3014543859 以及收件人：Philip Kreiter。

Sincerely, /S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
[中譯] 誠摯地, /S/
Francis Godwin
製造品質辦公室 主任
合規辦公室
藥品評估與研究中心

Source: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/yangzhou-hr-plastic-daily-chemical-co-ltd-722736-03182026
[中譯] 資料來源：https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/yangzhou-hr-plastic-daily-chemical-co-ltd-722736-03182026