Shriram Institute for Industrial Research MARCS-CMS 597629 — April 15, 2020

 

Warning Letter 320-20-33

 

April 15, 2020

 

 Dear Dr. Chacko:

 

The U.S. Food and Drug Administration (FDA) inspected your contract testing laboratory, Shriram Institute for Industrial Research, FEI 3002808145, at 19 University Road, University Campus, Delhi, from October 15 to 22, 2019.

 

美國FDA于2019年10月15日至22日檢查了你們位于印度的Shriram Institute for Industrial Research生產(chǎn)場所。

 

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, 21 CFR parts 210 and 211, and significant deviations from CGMP for active pharmaceutical ingredients (API).

 

本警告信總結(jié)了制劑生產(chǎn)嚴(yán)重違反CGMP， 21CFR第210與211部分，以及原料藥生產(chǎn)嚴(yán)重違反CGMP的行為。

 

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drugs 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).

 

由于你們的生產(chǎn)、加工、包裝或保存的方法、場所或控制不符合CGMP要求，你們的藥品根據(jù)FDCA的501(a)(2)(B)以及21 U.S.C.351(a)(2)(B)被認(rèn)為是摻假藥品。

 

We reviewed your November 7, 2019, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

 

我們已詳細審核了你公司于2019年11月7日對FDA 483表格的回復(fù)，并此告知已收到后續(xù)通信。

 

During our inspection, our investigators observed specific violations and deviations including, but not limited to, the following.

 

檢查期間，我們的調(diào)查人員發(fā)現(xiàn)的具體問題包括但不僅限于以下：

 

Finished Drug Violations 制劑藥品違規(guī)

 

1. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(a)). 你公司未對計算機或相關(guān)系統(tǒng)實施適當(dāng)?shù)目刂疲_保只有經(jīng)過授權(quán)的人員才可修改主生產(chǎn)和檢測記錄，或其它記錄（21 CFR 211.68(a)）。

 

Your firm serves as a contract testing laboratory analyzing both API and drug products. Your firm had not enabled the audit trail function on high-performance liquid chromatography (HPLC) units until on orabout October 11, 2019, when this FDA inspection was announced. Your analyst acknowledged during the inspection that the audit trail function on the HPLCs units was not enabled until October 2019. This was a repeat observation of your August 2016 FDA inspection.

 

你公司是一個合同檢測實驗室，分析API和制劑。你公司在2019年10月11日收到本次FDA檢查通知以前均未激活HPLC上的審計追蹤功能。你們的化驗員在檢查中承認(rèn)在2019年10月之前HPLC上審計追蹤功能未激活。這是2016年8月FDA檢查中的重復(fù)缺陷。

 

Despite written commitments after that inspection to install audit trails, you failed to enable audit trail functions on multiple analytical instruments, including your HPLC units.

 

雖然在檢查之后你們書面承諾要安裝審計追蹤，但你們有多臺分析儀器（包括HPLC單元上）并未激活審計追蹤功能。

 

Customers rely on the integrity of the laboratory data that you generate to make decisions regarding drug quality. It is important to maintain strict control over CGMP electronic data to ensure that all additions, deletions, or modifications of information in your electronic records are authorized and appropriately documented.

 

客戶依賴于你們產(chǎn)生的實驗室數(shù)據(jù)的完整性來做出藥品質(zhì)量方面的決策。為確保你們電子記錄中所有信息增加、刪除或修改均經(jīng)過批準(zhǔn)并有適當(dāng)記錄，保持對CGMP電子數(shù)據(jù)進行嚴(yán)格控制是很重要的。

 

In your response, your only corrective action was to designate an instrument engineer “to perform the routine inspection to proper performance of the equipment.” Your response is inadequate because it failed to describe specific controls you will implement to ensure audit trails remain enabled and the integrity of your data is not compromised.

 

在你們的回復(fù)中，你們僅有的糾正措施是指定一位儀器工程師“日常檢查儀器是否工作正常”。你們的回復(fù)是不充分的，因為其中未說明你們?yōu)榇_保審計追蹤保持激活，以及你們的數(shù)據(jù)完整性不受破壞而準(zhǔn)備實施的具體控制措施。

 

In response to this letter, provide: 在回復(fù)本函時請?zhí)峤?/span>

 

•      A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

 

•      一份對你們實驗室規(guī)范、程序、方法、設(shè)備、文件記錄和化驗員能力的全面獨立評估。根據(jù)該評估，提交一份詳細的補救計劃，并評估你們實驗室系統(tǒng)的有效性。

 

2. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures (21 CFR 211.22(d)). 你公司未能制訂并遵守書面的質(zhì)量部門適用職責(zé)與程序（21 CFR 211.22 (d)）。

 

Your Quality Unit (QU) failed to ensure that your laboratory personnel follow written procedures. For example, our investigators observed at least (b)(4) samples tested between March 2019 and September 2019 in which out-of-specification (OOS) results were not investigated as required in your procedures. Your head of Quality Assurance informed our investigator during the inspection that failures are investigated only upon customer request. Additionally, our investigators observed procedures not followed for review of analytical logbooks and results.

 

你們的質(zhì)量部門（QU）未能確保你們實驗室人員遵守書面程序。例如，我們的檢查員發(fā)現(xiàn)在2019年3月至2019年9月之間的檢測中至少有XX個樣品為OOS結(jié)果，但未按你們的程序要求進行調(diào)查。你們的QA領(lǐng)導(dǎo)在檢查期間告訴我們檢查員只有在客戶要求時才會對失敗進行調(diào)查。另外，我們檢查員發(fā)現(xiàn)你們亦未按程序要求對分析日志和結(jié)果進行審核。

 

These observations included: 這些缺陷包括：

 

•      Documentation errors covered by adhering new paper over the original value.

 

•      文件錯誤時在上面貼一張新紙蓋住原始值

 

•      Tests not recorded contemporaneously.

 

•      未同步記錄檢測情況

 

•      Sample identification not entered into your “Sample Record Register.”

 

•      樣品編號未錄入你們的“樣品記錄登記本”

 

•      Electronic data supporting analytical laboratory packets were not reviewed before you released final laboratory results.

 

•      在最終放行實驗室結(jié)果之前未審核支持分析實驗室包的電子數(shù)據(jù)

 

In your response, you stated that the procedure for OOS was not followed, but going forward all OOS results will be investigated to identify root causes. Additionally, you committed to conduct further CGMP documentation practice training for your analysts. Your response is inadequate because you failed to perform a risk assessment of your lack of following OOS procedures and poor documentation practices on products you tested for commercial release.

 

在你們的回復(fù)中，你們聲稱未執(zhí)行OOS程序，但將來會對所有OOS結(jié)果進行調(diào)查，找出根本原因。另外，你們承諾會對你們的化驗員進行深入CGMP文件規(guī)范培訓(xùn)。你們的回復(fù)是不充分的，因為你們未對不遵守OOS程序和商業(yè)產(chǎn)品檢測放行中不良文件規(guī)范進行風(fēng)險評估。

 

In response to this letter, provide: 在回復(fù)本函時請?zhí)峤?/span>

 

•      A retrospective, independent risk assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Includea detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, and contemporaneousrecords throughout your operation. Specify actions you will take in response tothe risk assessment, such as customer notifications.

 

•      一份對你們生產(chǎn)和實驗室操作所用文件記錄系統(tǒng)的回顧性獨立風(fēng)險評估，以確定哪些文件規(guī)范是不足的。要包括一份詳細的CAPA計劃，全面補救你公司的文件規(guī)范，確保你們會保存可追溯的、清晰的、完整的、原始的、準(zhǔn)確的和同步的所有操作記錄。說明你們對風(fēng)險評估結(jié)果準(zhǔn)備采取的措施，如通知客戶。

 

•      A retrospective, independent review of all OOS results for all tests. Identify any products which may be intended for the United States for the last three years from the initial date of inspection and a report summarizing the findings of the analysis, including the following for each OOS:

 

•      一份對所有OOS檢測結(jié)果的回顧性獨立審核報告。找出所有在檢查開始日之前三年內(nèi)可能銷售給美國的所有藥品，匯總分析發(fā)現(xiàn)的問題，包括每個OOS的以下內(nèi)容：

 

For all OOS results found by the retrospective review, identify any potential root cause and indicate if your customer was notified of the failure. Include the original test, date of test, testing result, customer, and reason for initiating an investigation.

 

對于回顧性審核中發(fā)現(xiàn)的所有OOS結(jié)果，找出所有潛在根本原因，說明是否將失敗情況通知你們客戶。要包括原始的檢測信息、檢測日期、檢測結(jié)果、客戶，以及啟動調(diào)查的原因。

 

•      The written response from your customers when notified of the testing failure(s).

 

•      在告訴你們客戶檢測不合格時，客戶的書面回復(fù)

 

•      A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function.The assessment should also include, but not be limited to:

 

•      一份全面的評估和補救計劃，確保你們QU被授予權(quán)力和資源可有效運作。評估亦應(yīng)包括但不僅限于以下：

 

A determination of whether procedures used by your firm are robust and appropriate

 

確定你公司所用程序是否穩(wěn)健恰當(dāng)

 

Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices

 

QU對整體操作進行監(jiān)管以評估是否遵守適當(dāng)規(guī)范的條款

 

A complete and final review of each batch and its related information before the QU disposition decision

 

QU在批處置決策前對每個批次及其相關(guān)信息進行全面最終審核

 

Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products

 

監(jiān)管和批準(zhǔn)調(diào)查，履行所有其它QU義務(wù)以確保所有產(chǎn)品的鑒別、含量、質(zhì)量和純度

 

Test Results Out-of-Specification 檢測結(jié)果OOS

 

For more information about handling failing, out-of-specification, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/media/71001/download.

 

關(guān)于失敗、OOS、OOT或其它計劃外結(jié)果處理和你們調(diào)查的文件記錄更多信息，參見FDA指南文件“藥品生產(chǎn)中OOS結(jié)果調(diào)查”。

 

Quality Systems 質(zhì)量體系

 

Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help in implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and211 at https://www.fda.gov/media/71023/download.

 

你公司的質(zhì)量體系是不充分的。參見FDA指南文件“藥物CGMP法規(guī)的質(zhì)量體系方法”，幫助你們實施質(zhì)量體系和風(fēng)險管理方法，從而符合21CFR第210和211的CGMP規(guī)范要求。

 

API Deviations API偏差

 

3. Failure to ensure that all test procedures are scientifically sound and appropriate to ensure that your raw materials and API conform to established standards of quality and/or purity. 未能確保所有檢測方法均科學(xué)合理恰當(dāng)，能確保你們的原料和API符合既定質(zhì)量標(biāo)準(zhǔn)和/或純度要求。

 

Our investigators observed many examples of United States Pharmacopeia (USP) labeled material which were tested on your analytical instruments without the completion of system suitability testing prior to analysis. For example, a sample of (b)(4) USP, batch (b)(4), was tested using an atomic absorption spectrometer on January 15, 2019, without confirming system suitability testing. This was a repeat observation from the August 2016 FDA inspection.

 

我們的檢查員發(fā)現(xiàn)許多標(biāo)有USP的物料在你們分析儀器上檢測時未完成系統(tǒng)適用性測試就開始進樣。例如，一個XX USP樣品批號為XX，在2019年1月15日采用原子吸收光譜進行檢測，檢測前未進行系統(tǒng)適用性測試。這是2016年8月FDA檢測中發(fā)現(xiàn)的重復(fù)缺陷。

 

After the previous inspection, your firm committed to performing system suitability testing on all analytical instruments “wherever required, prior to analysis” of USP tests. Additionally, your firm failed to document the testing method within laboratory records before issuing a certificate of analysis. You lacked adequate documentation to support that the USP labeled drug products were tested with USP methods.

 

上次檢查后，你公司承諾會在所有儀器上在USP檢測“需要時在分析之前”進行系統(tǒng)適用性測試。另外，你公司未在實驗室記錄中記錄檢驗方法就簽發(fā)了COA。你們沒有足夠的文件記錄支持標(biāo)示為USP的該藥品是采用USP方法檢測的。

 

System suitability testing determines whether requirements for precision are satisfied and ensures that the analytical instrument is fit for the intended testing before analyzing samples. It is critical that your system be demonstrated as suitable for use to avoid the possibility of samples erroneously passing when an instrument is not working properly.

 

系統(tǒng)適用性測試決定系統(tǒng)是否滿足精密度要求，在分析樣品之前確保分析儀器適合于檢測目的。證明你們的系統(tǒng)適合其用途，對于儀器工作不正常時避免樣品被錯判合格是非常關(guān)鍵的。

 

Customers rely on your laboratory data for critical information about the quality of drugs and their components. Thus, it is important that your analytical instruments are suitable for their intended use,and that you use appropriate test methods to enable your customers to make proper decisions (e.g., batch disposition).

 

客戶依賴于你們的實驗室數(shù)據(jù)中關(guān)于藥品及其成分的關(guān)鍵質(zhì)量信息。因此讓你們的分析儀器適合其既定用途，并且使用適當(dāng)?shù)臋z測方法讓你們的客戶做出正確決策（例如批處置）是非常重要的。

 

In your response, you committed to perform system suitability testing on your laboratory equipment prior to analysis. Additionally, you committed to inform your clients of the need to performmethod verification before conducting analysis. Your response lacked sufficient interim measures to ensure equipment is suitable and methods are robust while you continue to test drug products. Additionally, you did not conduct a risk assessment for USP tests performed without system suitability testing.

 

在你們的回復(fù)中，你們承諾要在分析之前對你們的實驗室儀器進行系統(tǒng)適用性檢測。另外，你們承諾會告知你們客戶在分析之前需要對方法進行確認(rèn)。你們的回復(fù)中沒有足夠的臨時措施確保你們繼續(xù)檢測藥品時設(shè)備是適用的，方法是穩(wěn)健的。還有你們未對無系統(tǒng)適用性的USP檢測進行風(fēng)險評估。

 

In response to this letter, provide: 在回復(fù)本函時請?zhí)峤?/span>

 

•      A retrospective, independent risk assessment addressing the hazards posed by providing USP test results of active pharmaceutical ingredients and drug products to clients without documenting the test method or performing system suitability testing on analytical instruments prior to testing. Specify actions you will take in response to the risk assessment, such as customer notifications.

 

•      一份回顧性獨立風(fēng)險評估，說明向客戶提供API和制劑的USP檢測結(jié)果卻沒有記錄檢測方法或檢測前在儀器上執(zhí)行系統(tǒng)適用性測試的危害。說明你們應(yīng)對風(fēng)險評估結(jié)果準(zhǔn)備采取的措施，如通知客戶。

 

•      A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system. This assessment should include, but not be limited to:

 

•      一份對你們實驗室規(guī)范、程序、方法、設(shè)備、文件記錄和化驗員能力的全面獨立評估。根據(jù)此次審核，提交一份詳細的補救計劃，同時評估你們實驗室系統(tǒng)的有效性。該評估應(yīng)包括但不僅限于

 

Your procedure for carrying out system suitability testing prior to analysis on your laboratory equipment

 

你們分析前在你們實驗室儀器上執(zhí)行系統(tǒng)適用性測試的程序

 

Your procedure for method verification for current and new methods performed within your laboratory

 

你們在你們實驗室對現(xiàn)有和新方法執(zhí)行方法確認(rèn)的程序

 

Your procedure for establishing responsibility for performing method verification between you and your clients

 

劃分你們和客戶之間方法確認(rèn)職責(zé)的程序

 

Repeat Observations at Facility 工廠重復(fù)缺陷

 

In a previous inspection, dated August 2-5, 2016, FDA cited similar CGMP observations. You proposed specific remediation for these observations in your response.

 

在之前20160802--20160805檢查中，F(xiàn)DA引用了類似的CGMP違規(guī)。在你們回程中，你們提出了對這些違規(guī)的具體補救方法。

 

Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.

 

重復(fù)失敗證明你們的執(zhí)行管理監(jiān)管和對藥品生產(chǎn)的控制是不充分的。

 

CGMP Consultant Recommended CGMP顧問建議

 

Based upon the nature of the violations and deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations as set forth in 21 CFR 211.34to assist your firm in meeting CGMP requirements.

 

鑒于我們在你公司所發(fā)現(xiàn)的違規(guī)情況，我們強烈建議你們使用一位有21 CFR 211.34所述資質(zhì)的顧問來協(xié)助你們公司符合CGMP要求。

 

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.

 

你們使用顧問并不能解除你們公司符合CGMP的義務(wù)。你們公司的高級管理層仍負有義務(wù)全面解決所有缺陷，確保持續(xù)CGMP符合性。

 

Data Integrity Remediation 數(shù)據(jù)完整性補救措施

 

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

 

你們的質(zhì)量體系不能充分確保數(shù)據(jù)的準(zhǔn)確性和完整性，無法支持你們生產(chǎn)的藥品的安全性、有效性和質(zhì)量。參見FDA指南文件“數(shù)據(jù)完整性和藥品GMP合規(guī)”指導(dǎo)建立和遵守CGMP合格數(shù)據(jù)完整性規(guī)范。

 

We strongly recommend that you retain a qualified consultant to assist in your remediation. In response to this letter, provide the following:

 

我們強烈建議你們聘用顧問對你們的操作進行審計并協(xié)助你們符合FDA要求。在回復(fù)此函時請?zhí)峤灰韵滦畔ⅲ?/span>

 

A.   A comprehensive investigation into the extent of theinaccuracies in data records and reporting. Your investigation should include: 一份對數(shù)據(jù)記錄和報告不準(zhǔn)確性程度的全面調(diào)查。你們的調(diào)查應(yīng)包括

 

l  A detailed investigation protocol and methodology; a summary of alll aboratories and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.

 

l  詳細的調(diào)查方案和方法學(xué)，所有實驗室、生產(chǎn)操作和評估所覆蓋的系統(tǒng)的總結(jié)，如有除外部分請論證

 

l  Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.

 

l  對現(xiàn)有和已離職員工進行面談，找出數(shù)據(jù)不準(zhǔn)確的程度、范圍和根本原因。我們建議這些面談由有資質(zhì)的第三方進行。

 

l  An assessment of the extent of data integrity deficiencies at yourfacility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe allparts of your facility’s operations in which you discovered data integrity lapses.

 

l  你們工廠數(shù)據(jù)完整性缺陷的程度的評估。識別出省略、修改、刪除、記錄銷毀、不同步記錄填寫和其它缺陷。說明你們已發(fā)現(xiàn)的數(shù)據(jù)完整性問題所涉及的工廠操作。

 

l  A comprehensive retrospective evaluation of the nature of the testing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluateall data integrity lapses.

 

l  一份對檢測和生產(chǎn)數(shù)據(jù)完整性缺陷情況的全面回顧性評估。我們建議由具備在已發(fā)現(xiàn)可能有問題的領(lǐng)域的專業(yè)能力的有資質(zhì)的第三方對所有數(shù)據(jù)完整性問題進行評估。

 

B.   A current risk assessment of the potential effects of the observed failures on the quality of drugs you tested for commercial release. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.

 

你們藥品質(zhì)量中所發(fā)現(xiàn)的不合格情況的潛在影響的當(dāng)前風(fēng)險評估。你們的評估應(yīng)包括由于受到數(shù)據(jù)完整性問題影響的藥品放行導(dǎo)致的患者風(fēng)險的分析，以及持續(xù)運營所具有的風(fēng)險。

 

C.  A management strategy for your firm that includesthe details of your global corrective action and preventive action plan. Your strategy should include: 你們公司的管理策略，包括你們?nèi)駽APA計劃詳細情況。你們的策略應(yīng)包括：

 

l  A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, and all data submitted to FDA.

 

l  詳細的CA計劃，描述你們準(zhǔn)備如何確保你們生成的所有數(shù)據(jù)的可靠性和完整性，包括分析數(shù)據(jù)、生產(chǎn)記錄和所有提交給FDA的數(shù)據(jù)。

 

l  A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action planis commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related data at your firm.

 

l  一份對你們數(shù)據(jù)完整性問題根本原因的全面描述，包括當(dāng)前行動計劃的范圍和深度與調(diào)查和風(fēng)險評估發(fā)現(xiàn)相稱的證據(jù)。說明負責(zé)數(shù)據(jù)完整性的人員是否還有能力影響你公司與CGMP有關(guān)或藥品申報數(shù)據(jù)。

 

l  Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of drugs, such as notifying your customers and conducting additional testing.

 

l  臨時措施，描述你們已采取或?qū)⒉扇∮脕肀Ｗo患者和確保你們藥品質(zhì)量的措施，如通知你們的客戶、執(zhí)行額外檢測。

 

l  Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.

 

l  長期措施，其中描述所有對用以確保你們公司數(shù)據(jù)完整性的程序、流程、方法、控制、系統(tǒng)、管理監(jiān)管和人力資源（例如培訓(xùn)、員工提高）的彌補和提升。

 

l  A status report for any of the above activities already underway or completed.

 

l  對上述活動已開展或已經(jīng)完成的狀態(tài)報告。

 

Conclusion 結(jié)論

 

The violations and deviations cited in this letterare not intended to be an all-inclusive list of violations and deviations that exist at your facility. You are responsible for investigating and determining the causes of these violations and deviations and for preventing their recurrence or the occurrence of other violations and deviations.

 

此函中所引用的違規(guī)并不是全部。你們有責(zé)任對這些偏差進行調(diào)查，確定原因，防止其再次發(fā)生，防止你們設(shè)施內(nèi)其它偏差的發(fā)生。

 

Until you correct all violations and deviations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new drug applications or supplements listing your firm as a contract testing laboratory.

 

在貴公司未能完成所有偏差糾正并且由我們確認(rèn)你們符合CGMP之前，F(xiàn)DA可能會擱置所有將你公司列為藥品生產(chǎn)的新申報和增補申報的批準(zhǔn)。

 

Failure to correct these violations and deviationsmay also result in the FDA refusing admission of articles manufactured by your clients and tested at Shriram Institute for Industrial Research, 19 University Road, University Campus, Delhi 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).

 

未能糾正這些偏差可能還會導(dǎo)致FDA依據(jù)FDCA第801(a)(3)條和21 U.S.C. 381(a)(3)拒絕接受在上述地址生產(chǎn)的產(chǎn)品進入美國。

 

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 deviations 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.

 

在收到此函后，請在15個工作日內(nèi)回復(fù)至本辦公室。在回復(fù)中說明自從檢查后，你們做了哪些工作來糾正你們的偏差，防止其再次發(fā)生。如果不能在15個工作日內(nèi)完成糾正措施，說明延遲的原因以及完成計劃。

 

Send your electronic reply toCDER-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 3002808145.

 

Sincerely,

/S/

 

Francis Godwin

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research