國內藥企有越來越多藥品在國際市場進行臨床試驗,接受來自國外的衛生主管機關的檢查的機會也日益增加,以下幾個關於國外監管環境的問與答與各位分享。
Success is liking yourself, liking what you do, and liking how you do it.
成功就是喜歡你自己,喜歡你自己做的事,喜歡你自己做事的方式。
- Maya Angelou
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➪哪些指南文件及法規構成在美國的GCP監管環境?
42 CFR Part 11 (Clinicaltrial.gov Regulations)
21 CFR Part 11 (Electronic Records/Signatures)
21 CFR Part 50 (Informed Consent of Clinical Subjects)
21 CRR Part 54 (Financial Disclosure for Clinical Investigators)
21 CFR Part 56 (Responsibilities of IRBs)
21 CFR Part 312 (Responsibilities of Investigators and Sponsors)
45 CFR Part 46 (Human Subject Protections)
FDA Guidance for Risk-based Monitoring; Investigator Responsibilities; Adverse Event Reporting to IRBs; Information Sheets for Institutional Review Boards and Clinical Investigators; and Institutional Review Boards, Clinical Investigators, and Sponsors; and Guidance for ICH E6(R2): Integrated Addendum to ICH E6(R1)
ICH E6(R2); Guideline for the Investigator’s Brochure; Guideline for Essential Documents for the Conduct of a Clinical Study
Regulation for Foreign Clinical Studies (that are not conducted under an IND application)
FDA CPGM (Compliance Program Guidance Manuals) (on GCP Inspections)
Form FDA 3674, Certification of Compliance (for INDs, NDAs, BLAs, PMAs, HDEs, and 510(k)s)
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➪歐美監管機構近年來的Inspection檢查重點趨勢為哪些面向呢?
USFDA Inspection遵循FDA Compliance Program Guidance Manuals, Program 7348.810 (Sponsors, CROs, and Monitors) and Program 7348.811 (Clinical Investigators)並強調數據完整性及受試者保護。
EMA Inspection傾向檢查包括eTMF和CAPA等電子資料庫,會沿著數據源的生命週期,由現場檢查回溯至CRO或Sponsor端,以確定數據的創建、維持、轉移、儲存等過程皆合乎完整性。
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➪在做臨床試驗遵循ICH E6(R2)指南時應特別注意的面向有哪些?
Investigator Oversight (section 4.2.5): investigator is responsible for supervising any individual or party who is delegated study tasks at the trial site
Requirement of Using Certified Copies (section 1.63): copies of original records are verified by a dated signature or generated validated process to have same information, including data that describe the context, content, and structure of the original
ALCOAC (section 4.9.0): good documentation practices - Attributable可溯源的, Legible易讀的, Contemporaneous及時的, Original原始的, Accurate準確的, and Complete完整的 – in source documents源文件, trial records試驗記錄, and audit trails稽查軌跡
Quality Management, Risk management, and Sponsor Oversight of Vendors (section 5.0)
Serious Breaches of the Trial Protocol require Sponsor to perform a root cause analysis and implement CAPAs (section 5.20.1)
Sponsor Trial Master File (TMF) management in maintaining records of the locations of the respective essential documents and processes to identify, search, and retrieval of the documents (section 8)
Monitoring Plans (section 1.64)
Electronic Systems and Data Handling (section 5.5.3)歡迎後臺回覆交流提問關於檢查準備過程中所遇到的實操問題,我們將在後續的公眾號文章中分享專家解惑及問題剖析。
☑️藥物研發全過程戰略諮詢
佈局海外-藥企進軍歐美市場的戰略規劃(一)
臨床研究監查稽查檢查實操問題解惑1┊2┊3┊4┊5┊6┊7┊8┊9
FDA新藥開發會議-WS衛森醫藥諮詢主管合伙人彼得·希曼博士的兩項倡議
風險管理攻略(一)研發項目及臨床試驗的風險管理
風險管理攻略(二)PEST分析模型
風險管理攻略(三)FEMA失效模式與影響分析
風險管理攻略(四)風險評估與戰略性稽查計劃
風險管理攻略(五)RACI分工模型表
藥物開發全過程質量管理-高階流程圖
☑️國際監管動態
盤點2019國際醫藥政策SEP┊OCT┊NOV-1┊NOV-2┊DEC-1┊DEC-2
盤點2020國際醫藥政策┊JAN-1┊JAN-2┊FEB-1┊FEB-2┊FEB-3┊MAR-1┊MAR-2
詳解┊歐盟藥監局2019年藥品審批報告
歐盟官宣!第1000次GCP Inspection
FDA生物研究監查項目(BIMO)數據分析
FDA基於風險的監查(RBM)更新指南Q&A
FDA藥審中心(CDER)的藥品生命周期安全性數據管理
FDA加強全球性藥品檢查項目以確保仿製藥安全性
FDA+MHRA: QMS & QbD
FDA+MHRA: GCP檢查程序類型及聯合檢查合作模式
FDA的GCP檢查案例分析-對稽查軌跡的審核思維
☑️藥物研發質量體系
從ICH Q10淺談藥品質量體系
Quality by Design (QbD) 質量源於設計
Kaizen!今天你進步了嗎?
受控文件管理好,臨床試驗才可靠
建多少不如建得巧的質量體系
質量體系初始培訓
藥物警戒初級培訓┊進階培訓
獨立數據監察委員會(一)┊(二)┊(三)┊(四)
臨床試驗的現場啟動考察(SIV)要點
面對來自監管機構檢查的準備及工作要點(一)
☑️申辦者質量體系中的委外業務管理
委外業務管理的來龍去脈(一)┊(二)
委外業務管理的來龍去脈(三)CRO質量協議
委外業務管理的來龍去脈(四)委外前的考慮
☑️近期法規時事
每月更新中國重點醫藥政策中英對照版2018 NOV┊DEC┊2019 JAN┊FEB┊MAR┊APR┊MAY┊JUN┊JUL┊AUG