小編按：本文是近期FDA發(fā)給捷克的API生產(chǎn)商VUAB的警告信，當(dāng)中有大量關(guān)于數(shù)據(jù)完整性的缺陷內(nèi)容，非常值得國(guó)內(nèi)的企業(yè)借鑒，而部分內(nèi)容也正對(duì)應(yīng)了CFDA近期出臺(tái)的《計(jì)算機(jī)化系統(tǒng)附錄》所提出的條款，可見(jiàn)全世界藥監(jiān)機(jī)構(gòu)對(duì)于計(jì)算機(jī)系統(tǒng)管理與數(shù)據(jù)完整性均持有一致的重視與要求！
| FDA Warning Letter on Data Integrity |
| FDA關(guān)于數(shù)據(jù)完整性的警告信 |
For authorities the integrity of data is an essential quality attribute in the manufacture of pharmaceutical products. After some serious deviations international authorities have moved the topic into the centre of their interest. In particular the US FDA issued serious violations in Warning Letters to the companies concerned.
對(duì)于藥監(jiān)當(dāng)局來(lái)說(shuō)，數(shù)據(jù)完整性是藥品生產(chǎn)中一個(gè)基本的質(zhì)量屬性。在發(fā)了一些嚴(yán)重的偏差后，國(guó)際藥監(jiān)當(dāng)局已經(jīng)將該問(wèn)題作為其關(guān)注的重點(diǎn)。尤其是美國(guó)FDA，他們?cè)诮o相關(guān)公司的警告信中指出了嚴(yán)重的違規(guī)情況。
In a current letter to the API manufacturer VUAB Pharma in the Czech Republic the inspector and the authority criticised multiple aspects with regard to "failure to prevent unauthorized access or change to data and to provide controls preventing data omissions":
在最近給捷克的API生產(chǎn)商VUAB的警告信中，檢查員和藥監(jiān)局批評(píng)了關(guān)于“未能阻止未經(jīng)授權(quán)的登錄和對(duì)數(shù)據(jù)的修改，未能防止數(shù)據(jù)丟失”的很多問(wèn)題：
The firm did not retain complete raw data from testing performed to assure the quality of API. The inspector revealed the firm did not properly maintain a back-up of HPLC chromatograms that form the basis of the product release decisions. The inspector revealed as well discrepancies between the printed chromatograms and the OQ protocol for the HPLC system, which is intended to demonstrate correct operation of the system (e.g. injection sequences and values to calculate relative standard deviation'
公司未能保持檢測(cè)過(guò)程中的完整原始數(shù)據(jù)來(lái)保證API的質(zhì)量。檢查員發(fā)現(xiàn)公司未能適當(dāng)維護(hù)HPLC色譜備份文件，使其成為產(chǎn)品放行決策的基礎(chǔ)。檢查員還發(fā)現(xiàn)打印出的色譜圖與HPLC系統(tǒng)的OQ方案不一致，該確認(rèn)是為了證明系統(tǒng)運(yùn)行的正確性（例如，進(jìn)樣序列和RSD計(jì)算值）
The quality unit was unable to retrieve the original electronic raw data because back-up discs were unreadable. The quality unit stated that back-up discs have been unreadable since at least 2013'
質(zhì)量部門(mén)未能恢復(fù)原始電子數(shù)據(jù)，因?yàn)閭浞荼P(pán)讀不出來(lái)。質(zhì)量部門(mén)說(shuō)備份盤(pán)至少2013年以來(lái)就讀不出來(lái)了
The inspector criticised that the firm does not have proper controls in place to prevent unauthorized manipulation of labs raw electronic data. The HPLC systems did not have access controls to prevent alteration or deletion of data. The HPLC software lacked an audit trail recording any changes to the data, including: previous entries, who made changes, and when changes were made'
檢查員批評(píng)了公司沒(méi)有設(shè)置適當(dāng)?shù)目刂苼?lái)防止未經(jīng)授權(quán)而對(duì)化驗(yàn)室原始電子數(shù)據(jù)進(jìn)行修改。HPLC系統(tǒng)沒(méi)有登錄權(quán)限控制來(lái)防止對(duì)數(shù)據(jù)的篡改和刪除。HPLC軟件缺乏審計(jì)追蹤來(lái)記錄所有對(duì)數(shù)據(jù)的修改，包括之前輸入、誰(shuí)做的修改、以及什么時(shí)間做的修改
The laboratory employees shared a common log-in and password to access the system'
化驗(yàn)室員工共用一個(gè)通用的用戶名和密碼來(lái)登錄系統(tǒng)
The firm response stated they are qualifying a new HPLC system which allows operator-specific passwords and has audit trail and back-up functions. The firm will implement as well a new electronic back-up system. FDA stated that the response lacks sufficient detail about systems and controls. Simply activating audit trail functions and instituting password controls is inadequate.'
公司回復(fù)說(shuō)他們對(duì)新的HPLC系統(tǒng)進(jìn)行了確認(rèn)，新的系統(tǒng)里不同操作員有不同的用戶名和密碼，有審計(jì)追蹤功能和備份功能。公司還將實(shí)施一個(gè)新的電子備份系統(tǒng)。FDA說(shuō)回復(fù)缺乏關(guān)于系統(tǒng)和控制的足夠的細(xì)節(jié)。只是激活審計(jì)追蹤功能和使用密碼控制是不足夠的
The firm failed to review historical data to ensure the quality of the products distributed to the US market'
公司未能對(duì)歷史數(shù)據(jù)進(jìn)行審核以保證在美國(guó)市場(chǎng)銷(xiāo)售的產(chǎn)品的質(zhì)量
In response to this list of deficiencies the FDA now expects the affected company to provide a comprehensive corrective action plan to the following points within 15 working days:
在在本缺陷清單 的回復(fù)中，F(xiàn)DA希望受影響的公司針對(duì)以下問(wèn)題點(diǎn)在15個(gè)工作日內(nèi)提供一份綜合的糾正措施計(jì)劃：
Information regarding changes in the reliability of the IT infrastructure, including improved IT systems, systems validation, revised procedures and retraining of employees'
關(guān)于IT設(shè)施的可靠性的變更的信息，包括改進(jìn)后的IT系統(tǒng)、系統(tǒng)驗(yàn)證、修訂后的程序和員工再培訓(xùn)
Procedures regarding passwords used to access the analytical instruments. All access levels for computerised systems should be clearly defined and documented in a written procedure'
關(guān)于用于登錄分析儀器的程序，計(jì)算機(jī)化系統(tǒng)的所有登錄級(jí)別均應(yīng)在書(shū)面程序中進(jìn)行清楚界定和記錄
A detailed summary of the steps taken to train the personnel on the proper use of computerised systems'
對(duì)人員恰當(dāng)使用計(jì)算機(jī)化系統(tǒng)的培訓(xùn)的步驟的詳細(xì)總結(jié)
來(lái)源：Julia/Candy，轉(zhuǎn)載請(qǐng)注明出處。免責(zé)聲明：編輯對(duì)上述內(nèi)容，對(duì)文中陳述、觀點(diǎn)判斷保持中立，不對(duì)所包含內(nèi)容的準(zhǔn)確性、可靠性或完整性提供任何明示或暗示的保證。僅作參考，并請(qǐng)各位自行承擔(dān)全部責(zé)任。
洛施德GMP咨詢
ID：soltoris
▲長(zhǎng)按識(shí)別二維碼關(guān)注
洛施德GMP咨詢于新加坡發(fā)展十多年，合作過(guò)眾多的跨國(guó)藥企，并在2012年于上海成立分公司，已為羅氏中國(guó)，齊魯制藥，華潤(rùn)三九，復(fù)星醫(yī)藥集團(tuán)，綠葉制藥，北大維信，協(xié)和發(fā)酵麒，威高集團(tuán)，香港澳美制藥等三十余家國(guó)內(nèi)外知名企業(yè)提供下列服務(wù)/產(chǎn)品:
GMP合規(guī)性咨詢
計(jì)算機(jī)系統(tǒng)驗(yàn)證
SISQP全面質(zhì)量管理系統(tǒng)
數(shù)據(jù)完整性審計(jì)
第三方GMP審計(jì)
企業(yè)GMP培訓(xùn)
洛施德GMP咨詢致力為客戶建設(shè)"合規(guī)，高效，可控"的質(zhì)量管理體系，協(xié)助客戶通過(guò)國(guó)內(nèi)外藥監(jiān)單位的GMP認(rèn)證。
