FDA警告信：佛山市晉雄科技
Warning Letter320-18-60June 26, 2018
Mr. Eric Qiu,General Manager
Foshan Jinxiong Technology Co., Ltd.
佛山市晉雄科技有限公司
Lijia Development Zone, Shang An Community,Danzao Town, Nanhai District
Foshan City, Guangdong Province 528223China
中國廣東省佛山市南海區丹灶鎮上安社區李家開發區528223
Dear Mr. Qiu:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Foshan Jinxiong Technology Co., Ltd. at Foshan City, Guangdong Province from August 15–18, 2017.
美國FDA於2017年8月15-18檢查了你們位於的廣東省佛山市的晉雄科技有限公司生產場所。
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
本警告信總結了製劑生產嚴重違反CGMP要求。參見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 product is 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).
由於你們的製劑生產、加工、包裝或保存的方法、場所或控制不符合CGMP要求，你們的製劑根據FDCA的501(a)(2)(B)以及21U.S.C. 351(a)(2)(B)被認為是摻假藥品。
We reviewed your September 3, 2017, response in detail.
我們已詳細審核了你公司2017年9月3日的回復。
During our inspection, our investigator observed specific violations including, but not limited to, the following.
檢查期間，我們的調查人員發現的具體問題包括但不僅限於以下：
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 identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).你公司未能放行前對每批藥品進行適當的化驗室檢測以確定其符合最終質量標準，包括每種成分的鑒別和含量（21 CFR 211.165(a)）。
Your firm is a contract manufacturer of over-the-counter (OTC) drug products marketed to(b)(4). You released multiple lots of OTC drug product without data to support their conformance to specifications,including identity and strength.
你公司是銷往XX的OTC藥品合同生產商。你們放行了多批OTC藥品卻並無數據支持其符合質量標準，包括鑒別和劑量。
In your response, you acknowledged that the testing you perform on finished drug product does not include identity and strength of the active ingredient, and that your clients may do this testing after you release the drug product lots. You also stated that you will arrange to have your finished drug product tested for identity and strength by an external laboratory once a year.
在你們的回復中，你們承認對成品所執行的檢測不包括活性成分的鑒別和劑量，你們的客戶在你們放行此藥品批次後可能執行了該檢測。你們還說，你們將會安排由一個外部化驗室每年一次檢測你們的成品的鑒別和劑量。
Your response was inadequate because, although you updated the finished product specifications to include identity and strength of(b)(4), you did not include a testing requirement of each lot prior to distribution,for identity and strength as a condition of lot release. You also did not provide active ingredient identity and strength test results of retain samples to support the quality of the drugs you have distributed to the US.
你們的回復是不充分的，因為儘管你們更新了成品的質量標準以包括XX的鑒別和劑量，但你們並未包括要求每批在放行前進行鑒別和劑量檢測的規定，將其作為批放行條件。你們亦未提交留樣的活性成分鑒別和劑量檢測要求以支持你們已銷往美國的藥品的質量。
In response to this letter, provide the following:
在回復此函時，請提交以下信息：
all chemical and microbial test methods and specifications used to analyze each lot of your OTC drug products prior to a lot disposition decision; and
所有批處理決策前用於分析每批OTC藥品的化學和微生物檢測方法和質量標準，以及
a summary of test results obtained from testing retain samples of all OTC drug products within expiry that have been distributed in the United States. These test results should include identity and strength of active ingredients, and all other appropriate chemical and microbial quality attributes.
一份所有已銷往美國仍在效期內的OTC藥品留樣檢測結果匯總。這些檢測結果應包括有活性成分的鑒別和劑量，以及所有其它適當的化學和微生物質量屬性。
2. Your firm failed to conductat least one test to verify the identity of each component of a drug product.Your firm also failed to establish the reliability of component supplier analyses on which you rely in lieu of certain tests through appropriate validation of supplier』s test results at appropriate intervals (21 CFR211.84(d)(1) and (2)).你公司未能執行至少一項檢測以鑒定每種藥品里的每種成分。你公司亦未通過對供應商的檢測結果以適當的時間間隔進行驗證來建立組份供應商分析的可靠性，卻依賴他們替代特定檢測。（21 CFR 211.84(d)(1) & (2)）。
Your firm failed to adequately test incoming components, including(b)(4), for their identity. Instead, your firm relied on certificates of analysis (COA) from unqualified suppliers.
你們公司未能充分檢測進廠物料，包括XX，的鑒定。相反，你們公司依賴於未經確認的供應商的COA。
In your response, you acknowledged that you do not performidentity testing on your incoming components, including your active ingredient,(b)(4). You also stated that you will seek out a laboratory that can perform identity testing on each batch of your active ingredient.
在你們的回復中，你們承諾你們並未對進廠組份，包括你們的活性成分XX執行鑒別測試。你們還聲稱你們會尋找一個可以執行你們活性成分逐批鑒別檢測的化驗室。
Your response was inadequate because you failed to indicate testing plans for other components of the drug product and your timeline for initiating identity testing on all incoming component lots. Your response also failed to indicate how you intend to establish the reliability of your suppliers if you plan to use their COA to assess the adequacy of components.
你們的回復是不充分的，因為你們並未說明藥品中其它成分的檢測計劃，以及你們啟動對所有進廠成分批次進行鑒別檢測的時間計劃。你們的回復亦未說明如果你們計劃使用供應商的COA用以評估組份的充分性的話，將如何建立你們供應商的可靠性。
In response to this letter, provide the following:
在回復此函時，請提交以下信息：
quality control release specifications for all incoming components, and the tests you perform for each lot;
所有進廠組份的質量控制放行標準，以及你們會對每個批次執行的檢測；
a summary of test results obtained from full testing of all your incoming components to validate the COA from each raw material manufacturer;
一份對你們所有進廠組份進行全檢所得檢測結果的匯總，以驗證每個原料生產商的COA；
a summary of your procedures for qualifying and overseeing the adequacy of contract facilities that test the OTC drug products you manufacture; and
一份你們確認和監管檢測你們所生產的OTC藥品的合同場所充分性的程序摘要；
a comprehensive, independent review of your material system to determine whether all containers, closures, and ingredients from each supplier are adequately qualified, assigned appropriate expiration or retest dates, and incoming material lot controls are adequate to prevent use of unsuitable containers, closures, and components.
一份對你們原料系統的全面獨立審核，以確認是否來自每一個供應商的所有容器密閉器和成分均充分確認、給定了適當的有效期或復驗期，並且進廠物料批次控制足以防止使用不適當的容器密閉器和組份。
3. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testingto determine appropriate storage conditions and expiration dates (21 CFR211.166(a)).你公司未能建立並遵守足夠的書面檢測程序用以評估藥品的穩定性屬性，並使用此穩定性檢測結果來確定適當的存貯條件和有效期（21 CFR 211.166(a)）。
You did not have adequate stability data to demonstrate that the chemical and microbiological properties of your drug products remain acceptable throughout their labeled expiry period. You established a(b)(4)shelf life based on the stability data of(b)(4)batch stored for up to 12 months. You also did not analyze this lot for active ingredient content.
你們沒有足夠的穩定性數據來證明你們藥品的化學和微生物屬性在其所標示的有效期內均可接受。你們基於XX批存貯至12個月的穩定性數據建立了一個XX時長的貨架期。你們亦未分析該批次的活性成分含量。
In your response, you stated that you will test the stability samples of finished drug product up to 36 months, according to the requirements of your stability procedure. However, your response was inadequate because your procedure does not include chemical tests, including active ingredient content.
在你們的回復中，你們聲稱你們會依據你們的穩定性程序要求檢測成品直到36個月的穩定性樣品。但是，你們的回復是不充分的，因為你們的程序並未包括有化學檢測，包括活性成分含量。
In response to this letter, provide the following:
在回復此函時，請提交以下信息：
a revised ongoing stability SOP, including but not limited to adding a test for active ingredient content at each stability station; and
一份修訂後的持續穩定性SOP，包括但不僅限於在每個穩定性檢測時間點增加活性成分含量檢測；以及
stabilitytest results of all drug products distributed in the United States within expiry using stability-indicating methods to determine if results meet specifications. If you obtain out-of-specification results, indicate the corrective actions you will take.
使用穩定性指示性方法檢測所有銷往美國仍在效期內的藥品所得的穩定性檢測結果，以確定是否結果符合質量標準。如果你們得到OOS結果，則說明你們將採取的糾正措施。
4. 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).你公司未能制訂批生產和批檢驗記錄，具備所生產每批藥品的與生產和檢測有關的完整信息(21 CFR 211.188)。
You lacked complete information related to the production and control of each lot. For example, you failed to have specific identification for each lot of component, and production equipment, used in manufacturing. You also failed to have unique lot or control numbers for the distributed drug product. You provided our investigator with a list of more than(b)(4)batches manufactured in 2017 that lacked this basic information.
你們缺少與每個批次生產和檢測有關的完整信息。例如，你們對生產所用每批組份和生產設備並無特定的標示。你們對所銷售藥品亦無唯一的批號或控制號。你們向我們調查人員提交了一份清單列出了2017年生產的XX余批次，缺少此基本信息。
In your response, you described your new lot numbering system and how you revised your production records. You also provided a copy ofthe revised production record.
在你們的回復中，你們描述了你們新的批號編製系統，以及你們將如何修改你們的批生產記錄。你們還提交了一份修訂後的批生產記錄的副本。
Responsibilities as a Contractor作為合同生產商的職責
Drugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.
藥品的生產必須符合CGMP要求。FDA了解許多藥品生產商會使用獨立的合同生產商，如生產場所、檢測化驗室、包裝商和貼標商。FDA將合同生產商視為生產商的延伸。
You are responsible for the quality of drugs you produce asa contract facility, regardless of agreements in place with product owners. Youare required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, andpurity. See FDA』s guidance document,Contract Manufacturing Arrangementsfor Drugs: Quality Agreements, athttps://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf.
作為合同場所，即使與藥品所有者簽訂有協議，但你們仍為你們所生產的藥品承擔質量職責。你們需要確保藥品依照FDCA第501(a)(2)(B)部分生產，滿足其安全、鑒別、劑量、質量和純度要求。參見FDA指南文件：藥品委託生產安排。
Quality Systems Guidance質量體系指南
See FDA』s guidance document,Quality Systems Approach to Pharmaceutical CGMP Regulations, for help implementing modern qualitysystems and risk management approaches to meet the requirements of CGMP regulations (21 CFR, parts 210 and 211), athttps://www.fda.gov/downloads/Drugs/Guidances/UCM070337.pdf.
參見FDA指南文件：葯業CGMP法規質量體系方法。
CGMP Consultant RecommendedCGMP顧問建議
Based upon the nature of the violations we identified atyour firm, we strongly recommend engaging a consultant qualified as set forthin 21 CFR 211.34, to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm』s obligation to comply with CGMP. Your firm』s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
依據我們在你們工廠發現的違規情況，我們強烈建議你們使用一位有21 CFR211.34所述資質的顧問來協助你們公司符合CGMP要求。你們使用顧問並不解除你們公司符合CGMP的義務。你們公司的高級管理層仍負有義務全面解決所有缺陷，確保持續CGMP符合性。
Conclusion結論
Violations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations.
此函中所引用的違規並不是全部。你們有責任對這些偏差進行調查，確定原因，防止其再次發生，防止你們設施內其它偏差的發生。
FDA placed your firm on Import Alert on February 14, 2018.
FDA已於2018年2月14日將你公司放在了進口禁令清單中。
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
在貴公司未能完成所有偏差糾正並且由我們確認你們符合CGMP之前，FDA可能會擱置所有將你公司列為藥品生產的新申報和增補申報的批准。
Failure to correct these violations may also result in FDA continuing to refuse admission of articles manufactured at Foshan Jinxiong Technology Co., Ltd. at Lijia Development Zone, Shang An Community, Danzao Town, Nanhai District, Foshan City, Guangdong Province into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles maybe subject to refusal 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 FD&C Act, 21 U.S.C.351(a)(2)(B).
未能糾正這些偏差可能還會導致FDA依據FDCA第801(a)(3)條和21U.S.C. 381(a)(3)拒絕接受在上述地址生產的產品進入美國。
After you receive this letter, respond to this office inwriting within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons fordelay and your schedule for completion.
在收到此函後，請在15個工作日內回復至本辦公室。在回復中說明自從檢查後，你們做了哪些工作來糾正你們的偏差，防止其再次發生。如果不能在15個工作日內完成糾正措施，說明延遲的原因以及完成計劃。
Cesar E. Matto
Senior Policy Advisor
U.S. Food and Drug Administration
White Oak Building 51, Room 4235
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Sincerely,
/S/
Francis Godwin
Acting Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Townley Inc.
10 West 33rdStreet, Suite 418,
New York, New York 10001
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