Warning letter 案例分析 (320-24-51) part 2

WARNING LETTER Jiangsu Hengrui Pharmaceuticals Co., Ltd. MARCS-CMS 679790 — July 11, 2024

此案一共有8條觀察事項，最後查廠結果被判定OAI並收到了警告信(Warning Letter)，承續 part1，這次討論江蘇恆瑞483缺失#4，對應到Warning Letter 第一條(如下)

Your firms quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality and purity (21 CFR 211.22)

Observation 4

The quality control unit lacks responsibility to approve all procedures or specifications impacting on the identity, strength, quality and purity of drug products, Specifically, 

品質單位沒有責任核准所有會對藥品特性，劑量，品質及純度產生影響的程序或規格，例如，

A).       The Quality Unit lacks adequate control over the issuance of controlled documents, such as production batch records, validation protocols and reports, change controls, and standard operating procedures. During the walkthrough of our inspection on 01/08/2024, we observed original executed pages of batch records, validation reports, change controls which had been discarded in a waste bin. When these original records found in the waste bin were compared to the archived official records, the information, such as production data did not always match.

品質單位並沒有充分控管管制文件的發放，例如生產批次文件，確效計畫書及其報告，變更管制及標準程序書。在2024/01/08日巡察時，觀察到原始執行的批次紀錄，確效報告及變更管制被丟棄在垃圾桶。這些被丟棄的文件跟已經被收錄的正式文件相比對，如生產數據的資料，並沒有一致。

B).       The Quality Unit lacks adequate control over the issuance of master production batch records purported to be controlled under your procedures PR-416 titled “Preparation of Batch Records, Issuing, Review and Filling Management Program”, effective date 06/20/2023 and QS-001 titled “Controlled Documents Management (DMS System) effective date 06/16/2023. During the inspection, it was observed that batch records are issue to production personnel using software DMS for control of records, however, production personnel can duplicate the batch record using a QR barcode on the printed batch record, which was determined to have occurred during the current inspection. For example, see above for information regarding original executed/ filled out batch record pages found in the firm’s trash bin during our walk through of the firm’s grounds.

品質單位缺乏充分管控現行的主生產批次記錄，相關程序書為PR-416 及QS-0001。稽核過程中，觀察到執行批次紀錄是運用DMS軟體發放到生產單位，然而，生產人員可以經由印製的批次紀錄上的QR code 來複製批次紀錄，例如上述說明原始執行或填寫的批次紀錄紙張可以在廠內垃圾桶內看到。

C).        Official eye exam results from medical professionals for visual inspection operators are not reviewed and managed by the Quality Unit.

醫療專業人對目視檢查人員進行的正式眼睛檢查結果並沒有經由品質單位審閱及管理。

D).       Parenteral drug products awaiting destruction in your waste area are not secure. During out walkthrough on 01/08/2024, we observed ██ doors to your waste building open and no personnel present.  This building is located directly across a public sidewalk and public street with an approximate 3.5-foot fence. Per your firm, the fence is secured with an alarm in case a private citizen climbs over the fence; however, during our inspection we found the alarm was not functional.

在廢棄區域等待報廢的針劑產品並沒有被安全的管控。2024/01/08查廠時，廢棄區域的門口是開放的且當時沒有人在現場。 這棟建築是直接坐落於街邊，有3.5 英尺高的圍牆，當有人翻越圍牆的時候會有警報產生達到安全性。但稽核時，發現警報系統是沒有功能的。

E).        There is no adequate data integrity program in place to include statistically sound comprehensive review of electronic data by the Quality Assurance Unit for standalone and network systems, to ensure completeness, consistency and accuracy of all chromatographic and non-chromatographic electronic data generated by Quality Control Laboratory.

沒有建立充分的數據完整性系統包含統計有效全面性審核電子數據，使品質保證單位能夠對單機或網路系統，確保品管實驗室產生的所有圖譜或非圖譜的電子數據