又一中國藥企被FDA掛網警告
來源：藥智網|一個桃子
據藥智新聞記者獲悉河南康迪藥械有限公司在2019年12月3日收到了FDA的警告信，河南康迪藥械有限公司是一家專做膏藥、貼劑等藥械類產品的生產廠家。信中指出該公司在美國銷售的關節止痛膏（Capsicum Plaster HOT）和利多卡因貼（1st Medx-Patch With 4% Lidocaine.）未經過FDA批准，並且對生產藥品的原料監管不嚴。近日FDA官網掛出了警告信全文。
FDA官網掛出的警告信具體內容如下：
December 3, 2019
Warning Letter 320-20-09
Dear Mr. Qi Lei:
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Henan Kangdi Medical Devices Co. Ltd., 3009271465, at SME Pioneer Park, No. 4, 2nd Area, Zhoukou, Henan, from March 4 to 7, 2019.
美國食品藥品監督管理局（FDA）於2019年3月4日至7日檢查了河南康迪藥械有限公司。
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
本警告函匯總了成品藥CGMP法規的重大違規。詳見美國聯邦法規第21卷，第210和211章。
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).
因為你們的方法、設施、生產工藝、包裝或者儲存的方式不符合CGMP法規，你們的藥品根據《聯邦食品、藥品和化妝品法》（FD&C）第501(a)(2)(B)章節，《美國法典》第21卷第351(a)(2)(B)節被認定為違規。
Your firm manufactures "Capsicum Plaster HOT" and " 1st Medx-Patch With 4% Lidocaine." These products are unapproved new drugs in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d). These violations are described in more detail below.
貴公司生產的關節止痛膏和利多卡因貼。這些產品是未經批准的新藥，違反了FD&C法案。根據法典，禁止將此類產品引入美國市場。下面將更詳細地描述這些違規行為。
We reviewed your March 22, 2019, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.
我們詳細審查了你們於2019年5月22日對FDA 483文件的回覆，並確認收到你們之後的回覆。
During our inspection, our investigator observed specific violations including, but not limited to, the following.
在檢查期間，我們的檢查員發現的具體違規包括但不限於如下。
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 the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
你們公司未能對每批藥品在出廠前進行適當的實驗室測定，以確定其是否符合藥品的最終規格，包括每種活性成分的特性和強度。
Your firm manufactures and distributes various over-the-counter (OTC) transdermal patch drug products such as "Capsicum Plaster HOT" pain relieving and " (b)(4) for the United States market. Our inspection found that you did not test your finished drug products to determine whether each batch met identity and strength specifications before being released to the U.S. market. Complete testing of each batch before release is an essential part of determining if a drug product batch meets its specifications.
貴你們公司為美國市場生產和銷售各種非處方（OTC）透皮貼劑，如關節止痛膏等一些產品。FDA檢查發現，在投放到美國市場之前，公司沒有對藥品成品進行檢驗，以確定每批產品是否符合特性和強度規格。每批藥品在放行前的完整測試是確定一批藥品是否符合規格的重要步驟。
The quality unit must be empowered to make final quality decisions. It is essential that the quality unit be enabled to provide timely oversight of all laboratory and manufacturing data that could impact product quality, whether or not lots have already been distributed. When making batch disposition decisions, the quality unit must be provided with all batch production and control records, including all deviations and test data, to enable a fully informed and appropriate decision regarding suitability for distribution. The quality unit must assure that drug products are fully tested for all critical attributes prior to release.
質量部門必須有權做出最終的質量決定。無論批次是否已經銷售，質量部門必須能及時監督所有可能影響產品質量的實驗室和生產數據。在做出批量處理決定時，質量部門必須提供所有批次生產和控制記錄，包括所有偏差和試驗數據，以便就是否適合銷售作出充分知情和適當的決定。質量部門必須確保藥品在出廠前經過所有關鍵屬性的全面測試。
In your response, you stated that you will search for a third-party testing laboratory with adequate capabilities. Additionally, you committed to test for the active ingredient in each batch of finished drug products sold within the U.S. market to ensure product specifications are met.
在你們的答覆中，表示將尋找一個有足夠能力的第三方檢測實驗室。此外，還承諾檢測在美國市場銷售的每批產品中的有效成分，以確保產品符合規範。
Your response is inadequate because you did not include information about your third-party testing laboratory including name and location, methods, or a detailed description of the tests they will conduct (e.g., identity, strength and purity). Furthermore, you did not provide how you will evaluate the capability of your third party to perform the intended tests. Additionally, you provided no testing documentation for finished drug product batches currently in the U.S. market.
你們的回覆是不充分的，因為沒有提供第三方檢測實驗室的信息，包括名稱和位置、檢測方法，或他們將進行的檢測的詳細描述（例如特性、強度和純度）。此外，也沒有提供如何評估第三方實驗室執行測試的能力和目前在美國市場上的產品批次的測試文件。
In response to this letter, provide:
針對本函，請提供：
A comprehensive and independent review of your laboratory practices, procedures, methods, equipment, and analyst competencies. Based on this review, provide a detailed corrective action and preventive action (CAPA) plan to fully remediate your laboratory system. Your plan should also include the procedures you will use to evaluate the effectiveness of the implemented CAP A plan.
對實驗室測試、程序、方法、設備和分析能力進行全面和獨立的審查。在此審查的基礎上，提供詳細的修正措施和預防措施（CAPA）計劃，以完全糾正實驗室測試系統。計劃還應包括將用於評估已實施的CAP A計劃的有效性的程序。
A list of all analytical test methods and specifications used to analyze each batch of your drug products before making the batch disposition decision. Include associated written procedures.
所有分析測試方法和規格的列表，用於在作出批次處理決定之前分析每批藥品。包括相關的書面程序。
A summary of test results obtained from retrospective testing of retain samples of all drug product batches currently in distribution in the U.S. Include test results for identity and strength of active ingredients, and all other appropriate chemical and microbial quality attributes. If you released any batch that was out of specification, indicate the corrective actions you will take, such as customer notifications and product recalls. Provide a timeline for completing this testing expeditiously.
對目前在美國銷售的所有藥品批次的保留樣品進行回顧性測試，包括活性成分的特性和強度的測試結果，以及所有其他適當的化學和微生物質量屬性。如果銷售了任何超出規格的批次，請說明將採取的糾正措施，如客戶通知和產品召回。提供快速完成測試的時間表。
A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture. Your summary should include, but not be limited to, your procedure to ensure that any test methods performed by a contract testing laboratory on your behalf are properly validated prior to use for batch analysis. Additionally, include the procedure to evaluate the capability of your third party to accomplish the testing they are contracted to perform.
一個計劃摘要，用於鑑定和監督測試你生產藥品的實驗室設施。摘要應包括但不限於以確保合作測試實驗室代表康迪執行的任何測試方法在用於批量分析之前得到正確驗證的資料。此外，還應包括評估第三方完成合同規定的測試能力的資料。
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 (2)).
康迪未能進行至少一次檢驗以驗證藥品的每一種成分的屬性。也未能在適當的時間間隔內驗證和確定原料供應商測試分析的可靠性。
You failed to test incoming active pharmaceutical ingredients (API) and other raw materials (e.g., (b)(4)) used to manufacture your drug products to determine their identity, purity, strength, and other appropriate quality attributes. Instead, our investigator observed your firm released API and other materials for use in manufacturing based solely on a visual inspection of the contents of material containers and a review of component suppliers analyses reports. You did not retain these suppliers' analysis reports, but discarded them after review. Additionally, you did not establish the reliability of your suppliers' analyses through appropriate validation. Your firm did not ensure that at least one specific identify test was conducted for each lot of your incoming materials. This violation was also observed during the December 2016 inspection, after which you committed to test incoming raw material.
你們未能測試用於生產藥品的原料藥（API）和其他原材料以確定其特性、純度、強度和其他適當的質量屬性。相反，FDA調查員觀察到貴公司發布的原料藥和其他用於製造的材料報告，僅僅是基於對材料容器內容物的目視檢查和對部分供應商的審查分析，且沒有保留這些供應商的分析報告，在審查後將其丟棄。此外，公司也沒有通過適當的驗證來確定供應商分析的可靠性，沒有保證每批來料都至少進行一次鑑定試驗。在2016年12月的檢查中也發現了這一違規行為，之後承諾對來料進行測試。
In your response, you stated your intent is to find a qualified third-party testing laboratory, revise your procedure for incoming material, and send to the third-party laboratory each lot of active ingredient used in drug products for U.S. supply.
在你們的回覆中，聲明你們想找到一個合格的第三方檢測實驗室，改正來料手續，並將用於美國供應的藥品中的每批活性成分提供給第三方實驗室。
Your response is inadequate because you did not commit to cease manufacturing drugs until the required testing of drug components is in place, and you did not conduct a risk assessment for products already in distribution in the United States. Furthermore, your response did not include the testing of raw materials, other than active ingredients, used in your finished drug products. Additionally, you failed to address how you will establish the reliability of your suppliers' analyses, and provided no documentation to support your CAPA plan.
對此你們的回覆是不充分的，因為回覆中沒有承諾在藥物成分的必要檢測到位之前停止生產藥物，而且沒有對已經在美國銷售的產品進行風險評估。此外，回復還不包括對成品藥中使用的原料藥（活性成分除外）的檢測。此外，也沒有說明如何建立供應商分析的可靠性，也沒有提供支持CAPA計劃的資料。
In response to this letter, provide:
針對本函，請提供：
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 have incoming material controls adequate to prevent use of unsuitable components, containers, and closures.
對原材料進行全面、獨立的審查，以確定每個供應商的所有容器、密封件和成分是否充分合格，是否指定了適當的有效期或重新測試日期，以及是否有足夠的來料控制措施，以防止使用不合適的組件、容器和密封件。
The chemical and microbiological quality control specifications you will use to determine disposition of each incoming lot of components before use in manufacturing.
將使用的化學和微生物質量控制規範來確定每批來料在製造前的存放。
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 testing results on your suppliers' certificates of analysis (COA) in lieu of testing each component
lot for purity, strength, and quality, specify how you will first establish the reliability and consistency of your suppliers' test results for these attributes 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.
描述如何測試每批原料是否符合所有適當的特性、強度、質量和純度規範。如果您打算接受供應商分析證書（COA）上的任何測試結果，而不是測試每批原料的純度、強度和質量，指定如何通過初始驗證和定期重新驗證，首先應建立供應商對這些屬性的測試結果的可靠性和一致性。此外，還應承諾始終對每批進廠原料進行至少一次特定的測試。
A summary of test results obtained from full testing of all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.
對所有原料進行全面測試，以評估各原料供應商提供的COA可靠性的測試結果匯總。包括描述COA驗證程序的標準操作程序。
3. 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)).
康迪未能保證該藥品的有效期是通過適當的穩定性試驗而確定的。
Your firm has not established an adequate stability program to support the (b)(4) expiration date assigned to your drug products. You lack sufficient data to demonstrate that the chemical and microbiological properties of your drug products will remain acceptable throughout their labeled expiry period.
康迪尚未制定足夠的穩定性計劃來支持貴公司給藥品指定的有效期。缺乏足夠的數據證明你方藥品的化學和微生物特性在標籤有效期內是有效的。
In your response, you committed to conduct stability testing on your drug products under accelerated conditions, and to ensure such testing are on samples held under appropriate temperature and humidity control.
在你們的回覆中，承諾加速對藥品進行穩定性測試，並確保在適當的溫度和溼度控制下對樣品進行此類測試。
Your response is inadequate because you failed to provide stability protocols, including all relevant quality attributes and acceptance criteria, and you did not provide assurance that your test methods will be adequate to assess drug stability. In addition, you did not clarify whether your stability testing will be conducted under real time conditions to support your OTC drug product expiry. Furthermore, you did not indicate any actions to ensure that all distributed drug product batches maintain their quality attributes through their labeled expiry.
對此回復是不充分的，因為沒有提供穩定性方案，包括所有相關的質量屬性和驗收標準，並且沒有提供保證測試方法將足以評估藥物穩定性。此外，沒有說明是否會在實時條件下進行穩定性測試，以支持非處方藥產品的有效期，也沒有指出任何措施來確保所有銷售的藥品批次在其標記的有效期內保持其有效性。
Based upon the lack of material testing, finished testing, and stability testing, there is minimal assurance that your drug manufacturing operations are capable of operating in a state of control.
由於缺乏原材料測試、成品測試和穩定性測試，因此無法保證藥品生產操作在受控狀態下運行。
In response to this letter, provide:
針對本函，請提供：
A comprehensive, independent assessment and CAP A plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:
全面、獨立的評估和CAPA計劃，以確保穩定計劃的充分性。補救計劃應包括但不限於：
o Stability indicating methods
o Stability studies for each drug product in its marketed container-closure system before distribution is permitted
o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid
o Detailed definition of the specific attributes to be tested at each station (timepoint)
穩定性指示方法。
允許銷售前每種藥品在市場上的容器密封系統中的穩定性研究。
每年將每種產品的代表性批次添加到計劃中，以確定保質期索賠是否有效。
每個時間點要測試的特定屬性的詳細定義。
All procedures that describe these and other elements of your remediated stability program.
描述這些和修正穩定性計劃的其他要求的所有過程。
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.
一份詳細的步驟，用於設計、驗證、維護、控制和監控每個製造過程，包括對批次內和批次間變化的警惕性監控，以確保持續的控制狀態。另外，包括設備和設施的鑑定計劃。
A description how top management will support quality control, quality assurance, and reliable operations, including but not limited to timely provision of oversight and resources to proactively address deficiencies in laboratories and manufacturing in order to support robust operations.
說明管理層將如何支持質量控制、質量保證和可靠運營，包括但不限於及時提供監督和資源，以主動解決實驗室和製造業的缺陷，從而支持穩健運營。
Quality Unit Authority質量主管部門
Significant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. See FDA's guidance document 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/71023/download.
本函中的重大發現表明康迪的質量部門未充分行使其權力和職責。康迪公司必須為質量部門提供適當的權力和充足的資源，以履行其職責，並始終如一地確保藥品質量。參見FDA的指導文件《藥品CGMP法規的質量體系方法》，以幫助實施質量體系和風險管理方法，以滿足CGMP法規要求。
Repeat Observations at Facility設施重複觀測
In a previous inspection, dated December 12 to 14, 2016, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.
在2016年12月12日至14日的前一次檢查中，FDA發現了類似的觀察結果。康迪在答覆中對這些意見提出了具體的補救措施。屢次失敗的結果表明，康迪對藥品生產的行政管理監督和控制是不夠的。
Use of Contract Manufacturers使用合同製造商
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.
藥品必須按照CGMP生產。FDA知道許多藥品製造商使用獨立的承包商，如生產設施、測試實驗室、包裝商和貼標商。FDA認為承包商是製造商的延伸。
You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA's guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.
無論與製造商達成什麼協議，康迪都要對藥品質量負責。必須確保藥品是按照FD&C法案生產的，以確保安全、特性、強度、質量和純度。參見FDA的指導文件《藥品合同製造安排：質量協議》
CGMP Consultant Recommended CGMP顧問推薦
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and that the consultant evaluates the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm's compliance status with FDA.
根據我們在康迪公司發現的違法行為的性質，如果康迪打算恢復為美國市場生產藥品，FDA強烈建議聘請一名符合要求的顧問，協助康迪滿足CGMP的要求。FDA還建議合格的顧問對CGMP合規性的整個操作進行全面審計，並建議顧問在尋求解決康迪合規狀況之前，評估糾正措施和預防措施的完成情況和有效性。
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.
使用顧問並不代表不用遵守CGMP的義務。康迪的執行管理層仍然負責解決所有缺陷和系統缺陷，以確保持續的CGMP合規性。
Unapproved New Drug Charges未經批准的新藥
"Capsicum Plaster HOT" and "1st Medx-Patch With Lidocaine 4%"
"Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" are drugs as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or as defined by section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are intended for use as external analgesics.
關節止痛膏和利多卡因貼是FD&C法案內定義的藥物，它們用於診斷、治療、緩解、治療或預防疾病，和/或《美國法典》內定義的藥物，它們意在影響身體的結構或任何功能。具體來說，這些產品是作為外部鎮痛劑使用的。
Examples of claims observed on the product labeling that establish the intended uses (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:
在產品標籤上觀察到的確定產品預期用途的示例包括但不限於：
"Capsicum Plaster HOT" Label Claims
"For long lasting relief of Rheumatism, Lumbago, Notalgia, and Sciatica, Arthralgia, Stiff Shoulder and Muscle Pain."
關節止痛膏標籤聲稱
用於長期緩解風溼、腰痛、痛、坐骨神經痛、關節痛、肩關節僵硬和肌肉疼痛
"1st Medx-Patch With Lidocaine 4%" Labeling Claims
"For the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, sprains, muscle soreness and stiffness."
利多卡因貼標籤聲稱
暫時緩解與關節炎、單純背痛、勞損、扭傷、肌肉酸痛和僵硬有關的肌肉和關節的輕微疼痛
OTC drug products such as "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" that are intended for external analgesic indications such as the relief of pain are being evaluated as part of the OTC Drug Review. They have been proposed to be classified as generally recognized as safe and effective and not misbranded under the Tentative Final Monograph (TFM) for External Analgesic Drug Products for Over-The-Counter Human Use (48 FR 5852, February 8, 1983). Pending the promulgation of a final rule, FDA generally does not intend to pursue regulatory action against products marketed in accordance with the conditions proposed in the TFM and each general condition in 21 CFR 330.1 unless a particular product poses a public health concern. Such marketing, however, is subject to the risk that a final rule may require reformulation and/or relabeling or FDA approval through the "new drug" procedures of the FD&C Act (section 505). However, "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" do not meet these conditions for the reasons explained below.
非處方藥產品，如關節止痛膏和利多卡因貼，用於止痛等外部適應症，正在作為非處方藥審查的一部分進行評估。根據用於非處方人類使用的外部止痛藥物的暫定定論（TFM），這些藥物被認為是公認的安全有效的，並且沒有品牌錯誤。在最終條例頒布之前，FDA一般不打算對根據TFM中提出的條件和每個一般條件銷售的產品採取監管行動，除非特定產品引起公眾健康問題。然而，此類營銷可能會面臨這樣的風險，即最終規定可能需要通過FD&C法案的「新藥」程序重新制定、重新標記或FD A批准。然而，關節止痛膏和利多卡因貼不符合這些條件，原因如下。
The formulation for "Capsicum Plaster HOT" includes capsicum in a concentration that exceeds what has been proposed in the External Analgesic TFM (see 48 FR 5852 at 5868, February 8, 1983). "Capsicum Plaster HOT" is labeled to contain Capsicum Extract 2.89%, while the External Analgesic TFM allows Capsicum in a concentration of 0.025% to 0.25%. Additionally, the product label for "Capsicum Plaster HOT" includes indications such as "long lasting relief of rheumatism, lumbago, notalgia, and sciatica" that are not proposed under this rulemaking or any rulemaking being considered under the OTC Drug Review.
關節止痛膏的配方包括濃度超過外部鎮痛劑TFM中提議的濃度，關節止痛膏標示含有2.89%的辣椒提取物，而外部鎮痛劑TFM允許濃度在0.025%到0.25%的濃度範圍內。此外，關節止痛膏的產品標籤包括本規則制定或OTC藥物審查中考慮的任何規則制定中未提出的「風溼、腰痛、痛和坐骨神經痛的長期緩解」等適應症。
The formulation for "1st Medx-Patch With Lidocaine 4%" includes lidocaine but this product is considered a counterirritant under the External Analgesic TFM because it is labeled for the temporary relief of minor aches and pains of muscles and joints. Lidocaine is not proposed as a counterirritant active ingredient in the External Analgesic TFM nor does the TFM propose the combination of anesthetic ingredients, such as lidocaine, with counterirritant ingredients (48 FR 5852 at 5868, February 8, 1983).
利多卡因貼的配方中包括利多卡因，但該產品被視為外部鎮痛劑中的一種抗刺激劑，因為它被標記為用於暫時緩解肌肉和關節的輕微疼痛。利多卡因不作為外部鎮痛劑中的抗刺激活性成分，TFM也不建議麻醉成分（如利多卡因）與抗刺激成分的組合。
Furthermore, we are not aware of any adequate and well controlled clinical trials in the published literature that support a determination that "Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" are generally recognized as safe and effective for their labeled indications. Additionally, we are not aware of similar OTC products as formulated and labeled that were available in the United States market on or before the inception of the OTC Drug Review.
此外，FDA還不知道在已發表的文獻中有任何充分且控制良好的臨床試驗支持關節止痛膏和利多卡因貼對於其標記適應症通常被認為是安全和有效的。此外，FDA不知道在非處方藥審查開始時或之前在美國市場上有類似的處方和標籤的非處方藥產品。
"Capsicum Plaster HOT" and "1st Medx-Patch With Lidocaine 4%," as labeled, are therefore new drugs within the meaning of section 201 (p) of the FD&C Act because they are not generally recognized among scientific experts as safe and effective for the drug uses described in its labeling. "New drugs" may not be introduced or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug.
關節止痛膏和利多卡因貼因此屬於FD&C法案所指的新藥，因為它們在科學專家中並不被公認為對其標籤中所述的藥物用途安全有效除非根據FD&C法案FDA批准的申請對新藥有效，否則新藥不得引入或交付用於美國貿易。
"Capsicum Plaster HOT" and " 1st Medx-Patch With Lidocaine 4%" are not the subject of approved new drug applications; therefore, marketing these products in the United States is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d) and violates section 505 of the FD&C Act.
關節止痛膏和利多卡因貼不屬於批准的新藥申請；因此，根據《聯邦食品藥品監督管理法》、《美國法典》禁止在美國銷售這些產品，並違反了《聯邦食品藥品監督管理法》第505條。
Conclusion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 these violations and for preventing their recurrence or the occurrence of other violations.
這封信中列舉的在康迪工廠內的違規行為並不止一個。您負責調查和確定這些違規行為的原因，並防止其再次發生或發生其他違規行為。
FDA placed your firm on Import Alert 66-40 on October 25; 2019.
食品和藥物管理局於2019年10月25日將貴公司置於進口警報66-40。
Until you correct all violations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new drug applications or supplements listing your firm as a drug manufacturer.
在康迪完全糾正所有違規行為並且FDA確認康迪遵守CGMP之前，FDA可能會拒絕批准任何新的藥物申請或將您的公司列為藥物製造商的補充廠商。
Failure to correct these violations may also result in the FDA continuing to refuse admission of articles manufactured at Henan Kangdi Medical Devices Co. Ltd., SME Pioneer Park, No. 4, 2nd Area, Zhoukou, Henan 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 may be subject to refusal of 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).
如果不糾正這些違規行為，FDA可能會繼續拒絕河南康迪醫療器械有限公司生產的藥品進入美國。本授權藥品可能會被拒絕入境，因為其製造過程中使用的方法和控制措施不符合CGMP。
After you receive this letter, respond to this office in writing 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 for delay and your schedule for completion.
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:
Joseph Lambert, Pharm.D.
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51 , Room 4235
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Please identify your response with FEI 3009271465.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research