摘 要 ▼
美國(guó)藥品評(píng)價(jià)和研究中心（CDER）于 2025 年 10 月 10 日給中國(guó)佛山某公司發(fā)送了一封警告信。信中指出該公司作為藥品制造商，向 FDA 提交的記錄顯示其生產(chǎn)過(guò)程嚴(yán)重違反CGMP，藥品被認(rèn)為摻假。信中列舉了多項(xiàng)違規(guī)行為，包括未對(duì)每批藥品進(jìn)行適當(dāng)?shù)膶?shí)驗(yàn)室檢測(cè)、未進(jìn)行穩(wěn)定性測(cè)試以確定有效期、未對(duì)原料進(jìn)行鑒別測(cè)試、未建立充分的生產(chǎn)和過(guò)程控制書(shū)面程序以及未準(zhǔn)備完整的批次生產(chǎn)和控制記錄等。FDA 已將該公司藥品列入進(jìn)口警報(bào)。
缺陷情況匯總?cè)缦拢?/span>
1、未進(jìn)行充分產(chǎn)品檢測(cè)：公司未對(duì)每批發(fā)往美國(guó)市場(chǎng)的非處方藥成品進(jìn)行足夠檢測(cè)，包括活性成分的鑒別和含量檢測(cè)，而檢測(cè)是確保藥品符合預(yù)定質(zhì)量屬性的關(guān)鍵環(huán)節(jié)，F(xiàn)DA認(rèn)為沒(méi)有充分的檢驗(yàn)，就沒(méi)有足夠的科學(xué)證據(jù)來(lái)保證藥品在放行前符合相應(yīng)的標(biāo)準(zhǔn)。
2、未確保藥品標(biāo)注的有效期得到適當(dāng)?shù)姆€(wěn)定性試驗(yàn)的支持：公司未進(jìn)行穩(wěn)定性測(cè)試，無(wú)法證明藥品活性成分在保質(zhì)期內(nèi)穩(wěn)定，也就難以保證藥品在整個(gè)保質(zhì)期內(nèi)符合既定的質(zhì)量標(biāo)準(zhǔn)。
3、未對(duì)藥品的每種組分進(jìn)行鑒別，也未確認(rèn)供應(yīng)商的檢驗(yàn)分析的可靠性：公司既未對(duì)藥品各成分進(jìn)行鑒別檢測(cè)，也未定期驗(yàn)證和確認(rèn)供應(yīng)商檢測(cè)分析的可靠性，缺乏對(duì)原料使用前符合規(guī)格的科學(xué)證據(jù)，可能導(dǎo)致使用受污染原料引發(fā)安全問(wèn)題。
4、未建立完善生產(chǎn)和工藝控制書(shū)面程序：公司未建立足夠的生產(chǎn)和過(guò)程控制書(shū)面程序，無(wú)法確保生產(chǎn)過(guò)程的可重復(fù)性和可控性，公司質(zhì)量部門(mén)未能確保產(chǎn)品銷(xiāo)售美國(guó)市場(chǎng)之前，生產(chǎn)工藝得到充分驗(yàn)證。
5、未準(zhǔn)備完整批生產(chǎn)和控制記錄：公司未記錄生產(chǎn)過(guò)程的所有重要步驟，無(wú)法證明生產(chǎn)過(guò)程的一致性和可追溯性，不利于對(duì)產(chǎn)品質(zhì)量問(wèn)題進(jìn)行調(diào)查。
【基礎(chǔ)信息】
Posted Date：2025.10.21
Letter lssue Date：2025.10.10
FEI：xxx
Firm name：xxx
Type establishment inspected：Drugs
Investigator：N/A
警告信正文 ▼
Your facility is registered with the United States Food and Drug Administration (FDA)as a manufacturer of over-the-counter (OTC)drug products.FDA has reviewed the records you submitted in response to our February 10,2025,request for records and other information pursuant to section 704(a)(4) of the Federal Food,Drug,and Cosmetic Act(FD&C Act) for your facility,XX Co.,Ltd,FEI 3017706051,at Industrial Building No.3,Ruichang Industrial Park,No.1,Honggang Section,Lishui Town,Nanhai District,Foshan,Guangdong,China.
你們公司作為非處方藥產(chǎn)品的生產(chǎn)商，已在美國(guó)食品藥品監(jiān)督管理局注冊(cè)。FDA已審閱了你們公司根據(jù)《聯(lián)邦食品、藥品和化妝品法案》第704(a)(4)條，針對(duì)我們于2025年2月10日要求的記錄和其他信息請(qǐng)求所提交的記錄及信息，涉及你們公司設(shè)施：×××。
This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals.See Title 21 Code of Federal Regulations,parts 210 and 211(21 CFR, parts 210 and 211).
本警告信概述了成品藥品現(xiàn)行生產(chǎn)質(zhì)量管理規(guī)范方面的重大違規(guī)行為。參見(jiàn)《聯(lián)邦法規(guī)匯編》第21篇第210和211部分。
Because your methods,facilities,or controls for manufacturing,processing,packing,or holding of drugs as described in your response to our 704(a)(4)request 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)).
由于你們公司在我們根據(jù)704(a)(4)條提出的要求的回復(fù)中描述的生產(chǎn)、加工、包裝或儲(chǔ)存藥品的方法、設(shè)施或控制不符合CGMP，因此你們的藥品依據(jù)《聯(lián)邦食品、藥品和化妝品法案》第501(a)(2)(B)條 [21 U.S.C. 351(a)(2)(B)] 的規(guī)定被視為摻假藥品。
Following review of records and other information provided pursuant to section 704(a)(4)of the FD&C Act,significant violations were observed including,but not limited to,the following:
根據(jù)對(duì)依據(jù)FD&C法案第704(a)(4)條提供的記錄和其他信息的審閱，發(fā)現(xiàn)了重大違規(guī)行為，包括但不限于以下方面：
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)).
你們公司未能對(duì)每批藥品在放行前進(jìn)行適當(dāng)?shù)膶?shí)驗(yàn)室檢測(cè)，以確定其符合藥品的最終質(zhì)量標(biāo)準(zhǔn)，包括每種活性成分的鑒別和含量（21 CFR 211.165(a））。
Your firm manufactures OTC drug products,including (b)(4).Your response to our request for records and other information under section 704(a)(4)indicated that you did not conduct adequate finished product testing on drug products shipped to the United States market.
你們公司生產(chǎn)非處方藥產(chǎn)品，包括(b)(4)。你們公司根據(jù)第704(a)(4)條對(duì)我們記錄和其他信息請(qǐng)求的回復(fù)表明，你們公司未對(duì)運(yùn)往美國(guó)市場(chǎng)的藥品進(jìn)行充分的成品檢驗(yàn)。
Testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use.Drug products must be tested for identity and strength of the active ingredient,prior to release and distribution.Without adequate testing,you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.
檢驗(yàn)是CGMP的重要組成部分，以確保你們生產(chǎn)的藥品符合所有適用于其預(yù)期用途的預(yù)定質(zhì)量屬性。藥品在放行和分銷(xiāo)前必須進(jìn)行活性成分鑒別和含量測(cè)定。沒(méi)有充分的檢驗(yàn)，你們就沒(méi)有足夠的科學(xué)證據(jù)來(lái)保證你們的藥品在放行前符合相應(yīng)的標(biāo)準(zhǔn)。
2.Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing(21 CFR 211.137(a)).
你們公司未能確保藥品標(biāo)注的有效期得到適當(dāng)?shù)姆€(wěn)定性試驗(yàn)的支持（21 CFR 211.137(a））。
Your response to our request for records and other information under section 704(a)(4)indicated that you did not perform stability testing.Therefore,you have not demonstrated that the active ingredient in your drug products is stable throughout its shelf life.
你們公司根據(jù)第704(a)(4)條對(duì)我們要求提供記錄和其他信息的回復(fù)表明，你們公司未進(jìn)行穩(wěn)定性試驗(yàn)。因此，你們未能證明藥品中的活性成分在其整個(gè)貨架期內(nèi)是穩(wěn)定的。
Without appropriate stability data,you cannot ensure your drug products meet established specifications and all pre- determined quality criteria throughout their assigned shelf-life.
沒(méi)有適當(dāng)?shù)姆€(wěn)定性數(shù)據(jù)，你們無(wú)法確保你們的藥品在其指定的貨架期內(nèi)符合既定的規(guī)格標(biāo)準(zhǔn)和所有預(yù)定的質(zhì)量標(biāo)準(zhǔn)。
3.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)).
你們公司未能對(duì)藥品的每種組分進(jìn)行至少一項(xiàng)測(cè)試來(lái)對(duì)其進(jìn)行鑒別。你們公司也未能定期驗(yàn)證和確認(rèn)你們組分供應(yīng)商的檢驗(yàn)分析的可靠性（21 CFR 211.84(d)(1) 和 211.84(d)(2））。
Your response to our request for records and other information under section 704(a)(4)indicated that you did not adequately test the identity of incoming components used in the manufacture of your drug products.You also did not demonstrate that you are testing your active ingredient (b)(4)for(b)(4).
你們公司根據(jù)第704(a)(4)條對(duì)我們記錄和其他信息請(qǐng)求的回復(fù)表明，你們公司未對(duì)用于生產(chǎn)藥品的進(jìn)廠物料進(jìn)行充分的鑒別檢測(cè)。你們也未能證明你們正在對(duì)活性成分(b)(4)進(jìn)行(b)(4)檢測(cè)。
Without adequate testing you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of your drug products.As a manufacturer,you have a responsibility to sample,test,and examine drug components before use in production to assure adequate quality,including testing for the presence of (b)(4) in (b)(4).
沒(méi)有充分的測(cè)試，你們就沒(méi)有科學(xué)證據(jù)表明你們的原材料在用于藥品生產(chǎn)前符合相應(yīng)的標(biāo)準(zhǔn)。作為生產(chǎn)商，你們有責(zé)任在生產(chǎn)使用前對(duì)藥品組分進(jìn)行取樣、測(cè)試和檢查，以確保足夠的質(zhì)量，包括檢測(cè)(b)(4)中是否存在(b)(4)。
The use of(b)(4) contaminated with(b)(4) has resulted in various lethal poisoning incidents in humans worldwide.See FDA's guidance document(b)(4).
使用被(b)(4)污染的(b)(4)已在全球范圍內(nèi)導(dǎo)致多起致命的人類(lèi)中毒事件。參見(jiàn)FDA的指導(dǎo)文件(b)(4)。
4.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)) .
你們公司未能建立充分的生產(chǎn)和工藝控制書(shū)面程序，以確保你們生產(chǎn)的藥品具有其聲稱或標(biāo)注的擁有的鑒別、含量、質(zhì)量和純度（21 CFR 211.100(a））。
Your response to our request for records and other information under section 704(a)(4)indicated that you did not ensure that your manufacturing processes are reproducible and controlled to yield a product of uniform character and quality.For example,we requested the manufacturing process validation reports for your drug products.In response,you stated you have not validated the manufacturing process for your drug products.In addition,you distributed your drug products to the U.S.market prior to performing process validations.
你們公司根據(jù)第704(a)(4)條對(duì)我們記錄和其他信息請(qǐng)求的回復(fù)表明，你們公司未能確保你們的生產(chǎn)工藝具有可重現(xiàn)性和可控性，以生產(chǎn)出具有一致特性和質(zhì)量的產(chǎn)品。例如，我們?cè)竽銈兲峁┧幤返墓に囼?yàn)證報(bào)告。作為回復(fù)，你們聲明尚未對(duì)藥品的生產(chǎn)工藝進(jìn)行驗(yàn)證。此外，你們?cè)谶M(jìn)行工藝驗(yàn)證之前就將藥品分銷(xiāo)到美國(guó)市場(chǎng)。
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 and assure the quality of raw material inputs, in-process materials,and finished drugs.Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to determine whether an initia)() state of control has been established.
工藝驗(yàn)證評(píng)估工藝在整個(gè)生命周期中設(shè)計(jì)的合理性及可控狀態(tài)。生產(chǎn)工藝的每個(gè)重要階段都必須經(jīng)過(guò)適當(dāng)設(shè)計(jì)，并保證原料投入、中間體和成品藥的質(zhì)量。工藝確認(rèn)研究包括在每個(gè)重要工藝階段進(jìn)行密集的監(jiān)控和測(cè)試，以表征批內(nèi)變異，并對(duì)批次進(jìn)行評(píng)估以確定是否已建立初始的受控狀態(tài)。
Successful process qualification studies are necessary before commercial distribution.Thereafter,ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.
在商業(yè)分銷(xiāo)之前必須完成成功的工藝確認(rèn)研究。此后，需要對(duì)工藝性能和產(chǎn)品質(zhì)量進(jìn)行持續(xù)嚴(yán)格的監(jiān)督，以確保你們?cè)诋a(chǎn)品整個(gè)生命周期內(nèi)保持穩(wěn)定的生產(chǎn)操作。
We also note that your quality unit did not ensure that your manufacturing processes were adequately validated and in a state of control before releasing your OTC products for distribution to the U.S.market.
我們還注意到，你們的質(zhì)量部門(mén)未能確保在將你們的非處方產(chǎn)品放行分銷(xiāo)至美國(guó)市場(chǎng)之前，你們的生產(chǎn)工藝得到充分驗(yàn)證并處于受控狀態(tài)。
5.Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).
你們公司未能編制包含所生產(chǎn)每批藥品的生產(chǎn)和控制相關(guān)完整信息的批生產(chǎn)和控制記錄（21 CFR 211.188）。
Your response to our request for records and other information under section 704(a)(4)indicated that you did not document all important steps in your manufacturing process.For example,in your response,you stated“...this site does not prepare batch production records for every batch of our listed drug...”.This documentation is necessary to establish that manufacturing processes were consistently followed and are reproducible.Lack of complete records also deprives you of traceability of actions necessary for investigational purposes of any quality signals related to your products.
你們公司根據(jù)第704(a)(4)條對(duì)我們記錄和其他信息請(qǐng)求的回復(fù)表明，你們公司未記錄制造工藝中的所有重要步驟。例如，在你們的回復(fù)中，你們聲明“……本場(chǎng)地并未為每一批我們列出的藥品編制批生產(chǎn)記錄……”。這些文件對(duì)于確定制造工藝被持續(xù)遵循且具有可重現(xiàn)性是必要的。缺乏完整的記錄也使你們無(wú)法追溯與產(chǎn)品相關(guān)的任何質(zhì)量信號(hào)的調(diào)查所需行動(dòng)。
CGMP Consultant Recommended
建議聘請(qǐng)CGMP顧問(wèn)
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 audit1 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.
基于我們?cè)谀銈児景l(fā)現(xiàn)的違規(guī)性質(zhì)，你們應(yīng)當(dāng)聘請(qǐng)符合21 CFR 211.34規(guī)定資格的顧問(wèn)，來(lái)評(píng)估你們的操作并協(xié)助你們公司滿足CGMP要求。在你們尋求解決你們公司與FDA的合規(guī)狀態(tài)之前，該合格顧問(wèn)還應(yīng)對(duì)你們的整個(gè)操作進(jìn)行全面的六大系統(tǒng)審計(jì)¹，以評(píng)估其是否符合CGMP，并評(píng)估你們糾正措施和預(yù)防措施的完成情況和有效性。
Conclusion
結(jié)論
The violations cited in this letter are not intended to be an allinclusive 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.
本信中引用的違規(guī)行為并非意在列出你們?cè)O(shè)施存在的所有違規(guī)行為。你們有責(zé)任調(diào)查和確定任何違規(guī)行為的原因，并防止其再次發(fā)生或其他違規(guī)行為的發(fā)生。
FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on August 27,2025.
FDA已于2025年8月27日將來(lái)自你們公司的所有進(jìn)口到美國(guó)的藥用物質(zhì)和藥品列入進(jìn)口警示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 inspect to verify that you have completed corrective actions to any violations.
請(qǐng)立即糾正所有違規(guī)行為。在所有違規(guī)行為得到徹底解決且我們確認(rèn)你們符合CGMP之前，F(xiàn)DA可能會(huì)暫不批準(zhǔn)將你們公司列為藥品生產(chǎn)商的新申請(qǐng)或補(bǔ)充申請(qǐng)。我們可能會(huì)進(jìn)行檢查以核實(shí)你們已完成對(duì)所有違規(guī)行為的糾正措施。
Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Foshan Yiying Hygiene Products Co.,Ltd.,Industrial Building No.3,Ruichang Industrial Park,No.1,Honggang Section, Lishui Town,Nanhai District,Foshan,Guangdong,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 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).
未能解決任何違規(guī)行為也可能導(dǎo)致FDA根據(jù)FD&C法案第801(a)(3)條 [21 U.S.C. 381(a)(3)]，繼續(xù)拒絕允許在×× ×生產(chǎn)的物品進(jìn)入美國(guó)。根據(jù)此權(quán)限，那些似乎屬于摻假的物品可能會(huì)被扣留或拒絕入境，因?yàn)槠渖a(chǎn)中使用的方法和控制不符合FD&C法案第501(a)(2)(B)條 [21 U.S.C. 351(a)(2)(B)] 含義內(nèi)的CGMP。
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.
本信告知了我們的發(fā)現(xiàn)，并為您提供了解決上述缺陷的機(jī)會(huì)。收到此信后，請(qǐng)?jiān)?5個(gè)工作日內(nèi)書(shū)面回復(fù)本辦公室。具體說(shuō)明你們已采取哪些措施來(lái)解決任何違規(guī)行為并防止其再次發(fā)生。在回復(fù)此信時(shí)，你們可以提供額外的信息供我們考慮，以繼續(xù)評(píng)估你們的活動(dòng)和實(shí)踐。如果你們無(wú)法在15個(gè)工作日內(nèi)完成糾正措施，請(qǐng)說(shuō)明延遲的原因和你們的完成時(shí)間表。
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