ViaUPS Warning Letter 320-17-28
Return Receipt Requested
March 2, 2017
Mr. Deepak Rawat
Chief Executive Officer
Badrivishal Chemicals & Pharmaceuticals
Plot No. 13, Revenue Colony
Talegaon – Chakan Road
Talegaon Dabhade, Dist. Pune 410 507
Maharashtra
India
Dear Mr. Rawat:
The U.S. Food and Drug Administration (FDA)inspected your drug manufacturing facility, Badrivishal Chemicals &Pharmaceuticals at Gat No. 29, Village Jambwade (Induri), Post Sudumbre, TalukaMaval, Dist. Pune, Maharashtra, from August 16 to 19, 2016.
美國FDA於2016於8月16-19日檢查了貴公司位於馬哈拉施特拉的藥品生產場所。
This warning letter summarizes significant deviationsfrom current good manufacturing practice (CGMP) for active pharmaceuticalingredients (API).
本警告信總結了不符合原料藥（API）CGMP要求的嚴重違規情況。
Because your methods, facilities, or controls formanufacturing, processing, packing, or holding do not conform to CGMP, your APIare 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).
由於你們生產、加工、包裝和存貯藥品的方法、設施和控制不符合CGMP，根據FDAC501(a)(2)(B)和21U.S.C. 351(a)(2)(B) ，你們的藥品被認為是摻假藥。
We reviewed your September 8, 2016, response indetail.
我們詳細審核了你們於2016年9月8日所發的回覆。
During our inspection, our investigators observedspecific deviations including, but not limited to, the following.
在我們檢查期間，我們的調查人員發現具體違規情況包括但不僅限於以下：
1. Failure to validate and monitorthe water purification system to ensure that water is of appropriate qualityand suitable for its intended use.
未能驗證和監測水純化系統以確保水具有適當的質量並適合其既定用途。
During the inspection, our investigators found thatyour water purification system was not adequately monitored and controlled.Because you use water as a drug component and for cleaning your facility andequipment, these failures pose significant risk to the safety of your drugs.
在我們檢查期間，我們的調查人員發現你們的水純化系統並未進行充分監測和控制。由於你們使用了水作為藥品組分，並用於場所和設備清潔，這些問題對你們藥品的安全性具有重大風險。
Source water 源水
You failed to test the source water for your (b)(4)water system. The source water emanates from a nearby river and passes throughfarmland, where it is subject to agricultural runoff and animal waste, beforereaching your facility. Your firm stores the source water in an (b)(4)tank that has a large (b)(4)-facing hole that is open to theenvironment. Your storage method does not protect your water from dirt andother contaminants, or from the ingress and proliferation of pests andobjectionable organisms.
你們未檢查你們XX水系統的源水。源水來自附近的一條河，該河流經農地，在到達你們工廠之前受到農產徑流和動物廢物的汙染。你們公司將源水存貯於XX罐中，該罐有一個很大的XX洞，直接連通環境。你們的存貯方法無法保護你們的水不受到髒物和其它汙染物的影響，無法保護其不受到蟲害和有害生物的侵入和滋生。
Sanitization and validation 消毒和驗證
You did not follow your own sanitization proceduresfor your (b)(4) water system. Your procedures specify (b)(4) ofsanitization at (b)(4), yet our investigators identified instances whereyou sanitized for as little as 10 minutes without justification.
你們的XX水系統沒有遵守你們自己的消毒程序。你們的程序說XX應按YY周期進行消毒，但我們調查人員發現你們未經論證只消毒10分鐘的情況。
During the inspection, you stated that in March 2016you initiated, but have not yet completed, a performance qualification of the (b)(4)water system. Your firm has used this unqualified system routinely since itsinstallation in 2014, despite having no scientific evidence that the system iscapable of producing water of adequate quality.
在檢查期間，你們聲稱你們於2016年3月開始了XX水系統的性能確認，但尚未完成。你們公司自2014年安裝後即開始常規使用此未經確認的系統，而不管其實你們並沒有科學證據證明該系統具備產生足夠質量水的能力。
Testing 檢測
Our investigators found that you were aware that thetotal aerobic microbial counts (TAMC) for all in-process water samples (b)(4)had exceeded your limit of (b)(4) colony forming units (cfu)/mL formultiple months. You failed to investigate these deviations.
我們的調查人員發現你們知道所有中控水樣XX已經持續多月超出你們的總有氧菌計數（TAMC）微生物限度XXCFU/ml，而你們並沒有對這些偏差進行調查。
Furthermore, your firm did not demonstrate an adequateunderstanding of the process that your (b)(4) water system relies on tokill microorganisms. (b)(4) is typically (b)(4)sanitizationsteps. However, you only use (b)(4) to reduce TAMC to acceptable levelsin the (b)(4) water. This suggests that it is a critical step in yourprocess, but you did not consider operating parameters that affect performance,such as water flow rate, (b)(4), water (b)(4), and(b)(4)age. Additionally, your interpretation of your results is confounded bythe fact that your methods are not verified.
另外，你們公司並沒有證據證明你們對XX水系統所依賴的微生物殺滅系統有足夠的了解，證明其是常規的XX消毒步驟。你們僅僅使用了XX來降低XX水中TAMC至可接受水平。這表明其在你們水處理工藝中是一個關鍵的步驟，但你們未考慮其影響性能的操作參考，如水流速度、XX、水YY和ZZ使用時長。另外，你們對你們結果的解釋受到你們的方法未經確認的事實的影響。
In your response, you committed to testing your sourcewater for microbiological contamination. You indicated that you setmicrobial limits of (b)(4) cfu/mL for the source water, and that youremoved the microbial limits for the in-process samples of your (b)(4)water system.
在你們的回覆中，你們承諾將測試你們源水中微生物汙染。你們說你們設定了源水微生物限度為XX CFU/ml，你們刪除了你們XX水系統裡中控樣品的微生物限度。
Your response is inadequate. You failed to providesufficient detail about how you will remediate your (b)(4) water system.In response to this letter, provide:
你們的回覆是不充分的。你們未能提供如何彌補你們的XX水系統的足夠細節。在回復此函時，請提交：
a plan to address the open (b)(4) source-water storage tank
一份計劃，解決開放式XX源水貯罐
a status update of the performance qualification that you initiated in March 2016
你們於2016年3月開始的性能確認狀態更新
corrective and preventive actions if source water test results exceed the limits
如果源水檢測結果超出限度的CAPA
scientific rationale for setting microbial limits
設定微生物限度的科學合理性
Contaminated (b)(4) water has been the rootcause of multiple recalls by other drug manufacturers of non-sterile (b)(4)liquids, including instances of adulteration with Burkholderiacepacia,an opportunistic pathogen. Therefore, it is imperative that appropriate actionand alert limits be established based on validation data; these limits must below enough to signal significant changes from normal operating conditions.
在其它非無菌XX液體製劑生產商多起召回中，受到汙染的XX水是根本原因，其中包括洋蔥伯克霍爾德菌，一種機會性病原體。因此，根據驗證數據建立適當的行動限和警戒限是一種經驗方法，這些限度必須足夠低以在正常操作條件下區別重大變化。
ViaUPS Warning Letter 320-17-27
Return Receipt Requested
March 2, 2017
Ms. Jocelyn (Jun) Ning
Owner
Lumis Global Pharmaceuticals Co. Ltd.
Unit 305 Huishang Mansion Building A
2 Wudayuan Road Donghu New Technology Development Zone
Wuhan, Hubei, 430073
China
Dear Ms. Ning:
The U.S. Food and Drug Administration (FDA)inspected your drug manufacturing facility, Lumis Global Pharmaceuticals Co.Ltd. at Unit 305 Huishang Mansion Building A, 2 Wudayuan Road Donghu NewTechnology Development Zone, Wuhan, from September 26 to 28, 2016.
美國FDA於2016於9月26-28日檢查了貴公司位於武漢市東湖新技術開發區武大園路2號徽商大廈A-305的藥品生產場所簡德明康藥業（武漢）有限公司。
This warning letter summarizes significant deviationsfrom current good manufacturing practice (CGMP) for active pharmaceuticalingredients (API).
本警告信總結了不符合原料藥（API）CGMP要求的嚴重違規情況。
Because your methods, facilities, or controls formanufacturing, processing, packing, or holding do not conform to CGMP, your APIare 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).
由於你們生產、加工、包裝和存貯藥品的方法、設施和控制不符合CGMP，根據FDAC501(a)(2)(B)和21U.S.C. 351(a)(2)(B) ，你們的藥品被認為是摻假藥。
In addition, your gabapentin API is misbranded undersections 502(a) and 502(b)(1) of the FD&C Act, 21 U.S.C. 352(a) and352(b)(1).
另外，你們的加巴噴丁原料藥根據FDCA的502(a)和 502(b)(1) 部分和 21 U.S.C. 352(a)和352(b)(1)部分認定為冒牌藥。
We reviewed your November 9, 2016, response in detail.We note your response addressed some FDA observations, but did not address theissues noted below.
我們詳細審核了你們於2016年11月9日所發的回覆。我們注意到你們回覆中解決了一些FDA發現的缺陷，但並沒有解決以下問題：
During our inspection, our investigator observedspecific deviations including, but not limited to, the following.
在我們檢查期間，我們的調查人員發現具體違規情況包括但不僅限於以下：
CGMP Deviations CGMP問題
1. Failure totransfer all quality or regulatory information received from the APImanufacturer to your customers.
未能將所有從API生產商處收到的法規信息和質量信息轉達給你們客戶。
You omitted the name and address of the original APImanufacturers on the certificates of analysis (COA) you issued to yourcustomers, and did not include copies of the original batch certificate.
你們在你們籤發給客戶的COA上沒有寫上原始API生商的名稱和地址，也沒有附上原始的批分析報告副本。
For multiple API, you generated COA by copying andpasting analytical results from the original API manufacturers, replacing themanufacturers』 information with your letterhead, then issuing these COA to yourcustomers. You omitted critical information, including the originalmanufacturers』 names and addresses and the names, addresses, and telephonenumbers of laboratories that performed the testing.
你們通過複製粘貼原始API生產商分析結果的方式製作了多個API的COA，用你們的信箋抬頭替換掉了生產商的信息，然後將這些COA籤發給你們的客戶。你們沒有寫上關鍵信息，包括原始生產商的名稱和地址、實施檢測的化驗室的名稱、地址和電話號碼。
Customers and regulators rely on COA for information aboutthe quality and sourcing of drugs and their components. Omitting informationfrom COA compromises supply-chain accountability and traceability, and may putconsumers at risk.
客戶和法規人員依賴於COA來獲取藥品及其成分的質量和來源信息。在COA上不提供這些信息使得供應鏈可靠信和可追溯性受到損害，可能會將客戶置於風險之下。
2. Failure to controlthe API repackaging, relabeling, and holding operations in order to avoid mixups and loss of API identity.
未能控制API重新包裝、重新標籤和存貯操作以避免混淆和API識別性缺失。
Our FDA investigator documented unlabeled material inyour 「released for shipping」 area. You told the investigator that this materialwas not to be released to customers, but was in fact intended for destruction.
我們的FDA檢查人員記錄下了在你們「發貨放行」區的無標籤物料。你們告訴檢查人員說該物料並不是要放行給客戶，而是要進行銷毀的。
To avoid mix-ups between materials that can and cannotbe released, or between different API, you must repackage, relabel, and holdAPI under appropriate CGMP controls.
為了避免混淆可以放行和不可以放行的物料，避免混淆不同API，你們必須在恰當的CGMP控制下重新包裝、重新標籤以及存貯API。
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