第2 部 ctd の概要(サマリー)
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エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 1
2.1 CTD の目次
第 2部(モジュール 2)の目次
巻/巻数
2 第 2部(モジュール 2) CTD の概要 1 / 1
2.1 CTD の目次(第 2部から第 5 部) 1 / 1
2.2 緒言 1 / 1
2.3 品質に関する概要 1 / 1
緒言 1 / 1
2.3.S. 原薬 1 / 1
2.3.S.1 一般情報 1 / 1
2.3.S.2 製造 1 / 1
2.3.S.3 特性 1 / 1
2.3.S.4 原薬の管理 1 / 1
2.3.S.5 標準品または標準物質 1 / 1
2.3.S.6 容器及び施栓系 1 / 1
2.3.S.7 安定性 1 / 1
2.3.P 製剤 1 / 1
2.3.P.1 製剤の処方 1 / 1
2.3.P.2 製剤開発の経緯 1 / 1
2.3.P.3 製造 1 / 1
2.3.P.4 添加剤の管理 1 / 1
2.3.P.5 製剤の管理 1 / 1
2.3.P.6 標準品または標準物質 1 / 1
2.3.P.7 容器及び施栓系 1 / 1
2.3.P.8 安定性 1 / 1
2.3.A その他 1 / 1
2.3.A.1 製造施設及び設備 1 / 1
2.3.A.2 外来性感染性物質の安全性評価 1 / 1
2.3.A.3 添加剤 1 / 1
2.3.R 各極の要求資料
2.4 非臨床試験の概括評価 1 / 1
2.4.1 非臨床試験計画概略 1 / 1
2.4.2 薬理試験 1 / 1
2.4.3 薬物動態試験 1 / 1
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 2
巻/巻数
2.4.4 毒性試験 1 / 1
2.4.5 総括及び結論 1 / 1
2.4.6 参考文献 1 / 1
2.5 臨床に関する概括評価 1 / 1
2.5.1 製品開発の根拠 1 / 1
2.5.2 生物薬剤学に関する概括評価 1 / 1
2.5.3 臨床薬理に関する概括評価 1 / 1
2.5.4 有効性に関する概括評価 1 / 1
2.5.5 安全性に関する概括評価 1 / 1
2.5.6 リスクとベネフィットに関する結論 1 / 1
2.6 非臨床試験の概要文及び概要表 1 / 1
2.6.1 緒言 1 / 1
2.6.2 薬理試験の概要文 1 / 1
2.6.3 薬理試験の概要表 1 / 1
2.6.4 薬物動態試験の概要文 1 / 1
2.6.5 薬物動態試験の概要表 1 / 1
2.6.6 毒性試験の概要文 1 / 1
2.6.7 毒性試験の概要表 1 / 1
2.7 臨床概要 1 / 1
2.7.1 生物薬剤学及び関連する分析法の概略 1 / 1
2.7.1.1 背景及び概観 1 / 1
2.7.1.2 個々の試験結果の要約 1 / 1
2.7.1.3 全試験を通しての結果の比較と解析 1 / 1
2.7.1.4 付録 1 / 1
2.7.2 臨床薬理の概要 1 / 1
2.7.2.1 背景及び概観 1 / 1
2.7.2.2 個々の試験結果の要約 1 / 1
2.7.2.3 全試験を通しての結果の比較と解析 1 / 1
2.7.2.4 特別な試験 1 / 1
2.7.2.5 付録 1 / 1
2.7.3 臨床的有効性の概要 1 / 1
2.7.3.1 背景及び概観 1 / 1
2.7.3.2 個々の試験結果の要約 1 / 1
2.7.3.3 全試験を通しての結果の比較と解析 1 / 1
2.7.3.4 推奨用量・用法に関する臨床情報の解析 1 / 1
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 3
巻/巻数
2.7.3.5 効果の持続、耐薬性 1 / 1
2.7.3.6 付録 1 / 1
2.7.4 臨床的安全性の概要 1 / 1
2.7.4.1 医薬品への暴露 1 / 1
2.7.4.2 有害事象 1 / 1
2.7.4.3 臨床検査値の評価 1 / 1
2.7.4.4 バイタルサイン、身体的所見及び安全性に関連する他の観察項目 1 / 1
2.7.4.5 特別な患者集団及び状況下における安全性 1 / 1
2.7.4.6 市販後データ 1 / 1
2.7.4.7 付録 1 / 1
2.7.5 参考文献 1 / 1
2.7.6 個々の試験のまとめ 1 / 1
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 4
第 3部(モジュール 3)の目次
巻/巻数
3 第 3部(モジュール 3) 品質に関する文書 1- 4 / 4
3.1 目次 1 / 4
3.2 データ又は試験報告書 1- 4 / 4
3.2.S. 原薬(Clofarabine、XXXXXXXXXXXXXXXXXX) 1- 2 / 4
3.2.S.1 一般情報 1 / 4
3.2.S.1.1 名称 1 / 4
3.2.S.1.2 構造 1 / 4
3.2.S.1.3 一般特性 1 / 4
3.2.S.2 製造 1 / 4
3.2.S.2.1 製造業者 1 / 4
3.2.S.2.2 製造方法及びプロセス・コントロール 1 / 4
Method Development & Validation Report: MDV-C-146.4 1 / 4
Method Development & Validation Report: MDV-C-146.7 1 / 4
Method Development & Validation Report: MDV-C-146.22 1 / 4
Method Development Report: MDV-C-146.28 1 / 4
SOP: XXXXXXXX, Title: HPLC Method for Analysis of XXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
1 / 4
SOP: XXXXXXXX, Title: Purity Determination of XXXXXXX Clofarabine
(XXXX) by HPLC
1 / 4
3.2.S.2.2 製造方法及びプロセス・コントロール(Ash) 1 / 4 3.2.S.2.3 原材料の管理 1 / 4
Method Development & Validation Report: MDV-C-146.6 1 / 4
Method Development & Validation Report: MDV-C-146.9 Amendment 1 1 / 4
Method Development & Validation Report: MDV-C-146.13 1 / 4
Method Development & Validation Report: MDV-C-146.17 1 / 4
SOP: XXXXXXXX, Title: IR SPECTROSCOPY 1 / 4
SOP: XXXXXXXX, Title: Calibration and Operation of the Mettler Toledo
Thermosystem -FP90/FP81HT Melting Point System
1 / 4
SOP: XXXXXXXX, Title: pH DETERMINATION 1 / 4
SOP: XXXXXXXX, Title: Physical Examination 1 / 4
SOP: XXXXXXXX, Title: REFRACTIVE INDEX 1 / 4
SOP: XXXXXXXX, Title: OPERATION AND CALIBRATION OF
RUDOLPH RESEARCH AUTOPOL V AUTOMATIC POLARIMETER
1 / 4
SOP: XXXXXXXX, Title: WATER DETERMINATION 1 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 5
巻/巻数
SOP: XXXXXXXX, Title: PURITY DETERMINATION OF XXXX OR
XXXXXX BY HPLC
1 / 4
SOP: XXXXXXXX, Title: Purity Determination of XXXXXXXXXXXXXX
XXXXXXX by HPLC
1 / 4
SOP: XXXXXXXX, Title: GC-FID DETERMINATION OF PURITY FOR
SOLVENTS
1 / 4
SOP: XXXXXXXX, Title: GC-FID DETERMINATION OF PURITY FOR
XXXXXXXXXXXXXXXX
1 / 4
3.2.S.2.4 重要工程の開発の経緯 1 / 4
3.2.S.2.4 重要工程の開発の経緯(XXXX) 1 / 4
Technical Report: Validation of XXXXXXXX Clofarabine
Assay by HPLC: 0027AD9101
1 / 4
3.2.S.2.5 プロセス・バリデーション/プロセス評価 1 / 4
Summary Report For The Process Validation For XXXX (Clofarabine)
Referencing Protocol: 4.134-0033
1 / 4
3.2.S.2.5 プロセス・バリデーション/プロセス評価 (XXXX) 1 / 4 PROCESS VALIDATION PROTOCOL (ASI # XXXXXX)
XXXXXXXX CLOFARABINE (XXXXXXXX) DRUG SUBSTANCE INTERMEDIATE PRODUCTION
1 / 4
PROCESS VALIDATION REPORT (ASI # XXXXXXXX) CLOFARABINE (XXXXXXXX) ACTIVE PHARMACEUTICAL INGREDIENT PRODUCTION
1 / 4
3.2.S.2.6 製造工程の開発の経緯 1 / 4 Clofarabine Process Development Report 1 / 4 CERTIFICATE OF ANALYSIS by XXXXXXXXXXXXXXX . Lot No:
XXXXXXXX 1 / 4
CERTIFICATE OF ANALYSIS by XXXXXXXXXXXXXXX . Lot No: XXXXXXXX
1 / 4
3.2.S.2.6 製造工程の開発の経緯(XXXX) 1 / 4
CERTIFICATE OF ANALYSIS by XXXXXXXX
XXXXXXXX . Lot No: XXXXXXXX
1 / 4
CERTIFICATE OF ANALYSIS by XXXXXXXX
XXXXXXXX . Lot No: XXXXXXXX
1 / 4
3.2.S.3 特性 1 / 4 3.2.S.3.1 構造その他の特性の解明 1 / 4 Research Report, Polymorph Screen of Clofarabine: Report No. R2012001.01 1 / 4
3.2.S.3.2 不純物 1 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 6
巻/巻数
3.2.S.4 原薬の管理 1 / 4
3.2.S.4.1 規格及び試験方法 1 / 4
3.2.S.4/3.2.S.4.1 原薬の管理 (XXX)/ 規格及び試験方法 (XXX) 1 / 4
3.2.S.4.2 試験方法 1 / 4
SOP: XXXXXXXX , Title: Endotoxin Testing 1 / 4
SOP: XXXXXXXX , Title: Residue on Ignition 1 / 4
SOP: XXXXXXXX , Title: Headspace GC Determination of
XXXXXXXX XXin Clofarabine
1 / 4
SOP: XXXXXXXX , Title: Determination of Residual Solvents in
Clofarabine (XXXXX) by Headspace GC
1 / 4
Analytical Test Procedure for Clofarabine Drug API (Revision 4): XXXXXX 1 / 4
Analytical Test Procedure for Clofarabine Drug API (Revision 4): XXXXXX 1 / 4
3.2.S.4.2 試験方法 (XXXX) 1 / 4
Analytical Test Procedure for Clofarabine Drug API
(Revision 4): XXXXXXX
1 / 4
Test Method pH Determination: XXXXXXX 1 / 4
Test Method Karl Fischer Moisture Analysis: XXXXXXX 1 / 4
Test Method Microbial Limits Testing: XXXXXXXX 1 / 4
Test Method Residual Solvent Analysis of XXXX or XXXX
by Headspace GC: XXXXXXXX
1 / 4
Test Method Percent Weight Based Assay of Clofarabine
(XXXX) or Clofarabine (XXXX) by HPLC: XXXXXXX
1 / 4
3.2.S.4.3 試験方法のバリデーション 2 / 4
Protocol: Method Validation of Clofarabine API and Clofarabine Drug
Product by High Performance Liquid Chromatography-Revision 4:
07TRSA144
2 / 4
Protocol Amendment: Method Validation of Clofarabine API and Clofarabine
Drug Product by High Performance Liquid Chromatography-Revision 4:
07TRSA144
2 / 4
Method Validation of Clofarabine API and Clofarabine Drug Product by
High Performance Liquid Chromatography-Revision 4: 07TRSA144
2 / 4
Protocol : Determination of the XXXXXXXX XXXXXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level using
High Performance Liquid Chromatography
Project No. 6074-5124 XXXXXXXX
2 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 7
巻/巻数
Protocol Amendment: Determination of the XXXXXXXX XXXXXXXX
for Clofarabine Degradation Impurities at the Limit of Quantification (LOQ)
Level using High Performance Liquid Chromatography
Project No. 6074-5124 XXXXXXXX
2 / 4
Determination of XXXXXXXX XXXXXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103
2 / 4
Addendum to Determination of the XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103 (Addendum 01)
2 / 4
Addendum to Determination of the XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103 (Addendum 02)
2 / 4
Validation Protocol of Clofarabine Process Impurities for Test Methods
XXXXXXX and XXXXXXX: 08TRSA010
2 / 4
Method Validation of Clofarabine Process Impurities for Test Methods
XXXXXXX and XXXXXXX: 08TRSA010
2 / 4
Method Development & Validation Report: MDV-C-146.23 2 / 4
Method Development & Validation Report: MDV-C-146.26 2 / 4
Method Development & Validation Report: MDV-C-146.27 2 / 4
エボルトラの純度試験 HPLC 法のシステム適合性(検出の確認)の検
討: IDCAD-12-025 試験報告書/試験計画書
2 / 4
3.2.S.4.3 試験方法のバリデーション(XXX) 2 / 4
Protocol: Method Validation of Clofarabine API and
Clofarabine Drug Product by High Performance Liquid
Chromatography-Revision4: 07TRSA144
2 / 4
Protocol Amendment: Method Validation of Clofarabine
API and Clofarabine Drug Product by High Performance
Liquid Chromatography-Revision4: 07TRSA144
2 / 4
Method Validation of Clofarabine API and Clofarabine
Drug Product by High Performance Liquid
Chromatography-Revision4: 07TRSA144
2 / 4
Protocol : Determination of the XXXXXXXX XXXX
for Clofarabine Degradation Impurities at the Limit of
Quantification (LOQ) Level using High Performance
2 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 8
巻/巻数
Liquid Chromatography
Project No. 6074-5124 XXXXXXXX XXXX
Protocol Amendment: Determination of the XXXXXXX X
XX XXX for Clofarabine Degradation Impurities at the
Limit of Quantification (LOQ) Level using High
Performance Liquid Chromatography: Project No. 6074-
5124 XXXXXXXX XXXX
2 / 4
Determination of XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification
(LOQ) Level Using High Performance Liquid
Chromatography: 07TRSA103
2 / 4
Addendum to Determination of the XXXXXXXX XXX
for Clofarabine Degradation Impurities at the Limit of
Quantification (LOQ) Level Using High Performance
Liquid Chromatography: 07TRSA103 (Addendum 01)
2 / 4
Addendum to Determination of the XXXXXXX XXXX
for Clofarabine Degradation Impurities at the Limit of
Quantification (LOQ) Level Using High Performance
Liquid Chromatography: 07TRSA103 (Addendum 02)
2 / 4
Validation Protocol of Clofarabine Process Impurities for
Test Methods XXXXXXX and XXXXXXX: 08TRSA010
2 / 4
Method Validation of Clofarabine Process Impurities for
Test Methods XXXXXXX and XXXXXXX: 08TRSA010
2 / 4
Validation of Headspace GC Method for Assay of Residual
Solvents in Clofarabine Drug Substance: Report-0142
Revision: 00
2 / 4
Amendment to the Validation of Headspace GC Method for
Residual Solvents in Clofarabine Drug Substance:
0027CM5008
2 / 4
Validation of a Head space GC Method for the Assay of
Residual Solvents in Clofarabine Drug Substance:
0027CM5009
2 / 4
3.2.S.4.4 ロット分析 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 9
巻/巻数
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
CERTIFICATE OF ANALYSIS Clofarabine XXXX Lot No: XXXXXXX 2 / 4
3.2.S.4.4 ロット分析(Ash) 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
Certificate of Analysis Lot No: XXXXXXX 2 / 4
3.2.S.4.5 規格及び試験方法の妥当性 2 / 4
Evoltra (clofarabine) EMEA/H/C/000613; Responses to Follow Up Measures
(Quality) FUM029, XXXXXXX
2 / 4
3.2.S.4.5 規格及び試験方法の妥当性 (XXXX) 2 / 4
3.2.S.5 標準品または標準物質 2 / 4
Certificate of Analysis Clofarabine Impurity Solution: XXXXXXX XXXX 2 / 4
Certificate of Analysis Clofarabine Impurity Solution: XXXXXXX XXXX 2 / 4
Certificate of Analysis Clofarabine Impurity Solution: XXXXXXX XXXX 2 / 4
Certificate of Analysis Clofarabine Impurity Solution: XXXXXXX XXXX 2 / 4
Certificate of Analysis Clofarabine Impurity Solution: XXXXXXX XXXX 2 / 4
Certificate of Analysis Primary Reference Standard Qualification: 2 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 10
巻/巻数
Lot No: XXXXXXX
PREPARATION OF CLOFARABINE REFERENCE STANDARD:
Batch No.: Lot No: XXXXXXX
2 / 4
3.2.S.6 容器及び施栓系 2 / 4
Container Closure System: XXXXXXX XXXXXXX 2 / 4
Container Closure System: XXXXXXX XXXXXXX 2 / 4
3.2.S.6 容器及び施栓系(XXXX) 2 / 4
RAW MATERIAL SPECIFICATIONS & TEST RECORD
FORM: XXXXX
2 / 4
RAW MATERIAL SPECIFICATIONS & TEST RECORD
FORM: XXXXX
2 / 4
RAW MATERIAL SPECIFICATIONS & TEST RECORD
FORM: XXXXX
2 / 4
3.2.S.7 安定性 2 / 4
3.2.S.7.1 安定性のまとめ及び結論 2 / 4
3.2.S.7/3.2.S.7.1 安定性 (XXX), 安定性のまとめ及び結論(XXX) 2 / 4
3.2.S.7.2 承認後の安定性試験計画の作成及び実施 2 / 4
3.2.S.7.2 承認後の安定性試験計画の作成及び実施 (XXX) 2 / 4
3.2.S.7.3 安定性データ 2 / 4
3.2.S.7.3 安定性データ (XXX) 2 / 4
3.2.P 製剤(XXXXXXX XXXXXXX XXXXXXX XXXXXXX) 3 - 4 / 4
3.2.P.1 製剤の処方 3 / 4
3.2.P.2 製剤開発の経緯 3 / 4
3.2.P.2.1 製剤成分 3 / 4
3.2.P.2.1.1 原薬 3 / 4
3.2.P.2.1.2 添加剤 3 / 4
3.2.P.2.2 製剤 3 / 4
Solubility of Clofarabine in Saline Solution 3 / 4
3.2.P.2.2.1 製剤設計 3 / 4
3.2.P.2.2.2 過量仕込み 3 / 4
3.2.P.2.2.3 物理学的及び生物学的性質 3 / 4
3.2.P.2.3 製造工程の開発の経緯 3 / 4
3.2.P.2.4 容器及び施栓系 3 / 4
XXXXXXX XXXXXXXXXXXXXX XXXXXXX 3 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 11
巻/巻数
3.2.P.2.5 微生物学的観点からみた特徴 3 / 4
Method Development of a Container Integrity Test by the Microbial Ingress
Method for Media Filled Vials: 1203-AXJ24-ILEX-RE 1
3 / 4
PROTOCOL FOR CONTAINER/CLOSURE INTEGRITY TESTING OF
MEDIA-FILLED VIALS: Protocol No. ILEX103003
3 / 4
3.2.P.2.6 溶解液や使用時の容器/用具との適合性 3 / 4
Clofarabine IV Bag Solution Stability Study: 0027AD8001 3 / 4
Analytical Report: Compatibility study between Clofarabine injection and
0.9% saline solution over a XXXX dosing period
3 / 4
3.2.P.3 製造 3 / 4
3.2.P.3.1 製造者 3 / 4
3.2.P.3.2 製造処方 3 / 4
3.2.P.3.2 製造処方(XXXXX) 3 / 4
3.2.P.3.3 製造工程及びプロセス・コントロール 3 / 4
Hot Water System P& ID 3 / 4
3.2.P.3.4 重要工程及び重要中間体の管理 3 / 4
3.2.P.3.4 重要工程及び重要中間体の管理(XXXXX) 3 / 3
3.2.P.3.5 プロセス・バリデーション/プロセス評価 3 / 4
Validation summary of Bl study in XXXXXX steam autoclave:
Protocol No: 1309.8.62
3 / 4
FINAL REPORT Amended
D(121)-Value Determination of XXXXXXXXXXXXXXXXXXXXXXXX
Suspension (XXXXXXXXXXXX. Lot No. XXXXXX) in Clofarabine
1mg/mL (Batch No. XXXXXX)
3 / 4
Liquid qualification summary of-The XXXXXX steam autoclave:
Protocol No: 1309.8.61
3 / 4
3.2.P.3.5 プロセス・バリデーション/プロセス評価(XXXX) 3 / 4
Filtration Sterilization Validation, Clofarabine Injection
Solution, Doc. # 0027CM9004
3 / 4
D-Value Determination For
XXXXXXXXXXXXXXXXXX in 1 mg/mL Clofarabine
Injection, Microbiology Report #. M200202
3 / 4
D(121)-Value Determination of XXXXXXXXXXXXXXXX
Suspension (XXXXXXXXXXXX. Lot No. XXXXXX) in
Clofarabine 1mg/mL (Batch No. XXXXXX)
3 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 12
巻/巻数
3.2.P.4 添加剤の管理 3 / 4
3.2.P.4.1 規格及び試験方法 3 / 4
3.2.P.4.2 試験方法 3 / 4
3.2.P.4.3 試験方法のバリデーション 3 / 4
3.2.P.4.4 規格及び試験方法の妥当性 3 / 4
3.2.P.4.5 ヒト又は動物起源の添加剤 3 / 4
3.2.P.4.6 新規添加剤 3 / 4
3.2.P.5 製剤の管理 3 / 4
3.2.P.5.1 規格及び試験方法 3 / 4
3.2.P.5/3.2.P.5.1 製剤の管理(XXX) / 規格及び試験方法 (XXX) 3 / 4
3.2.P.5.2 試験方法 3 / 4
Analytical Procedure Quality Control No: XXXXXXXX 3 / 4
Analytical Test Procedure for Clofarabine Drug Product (1mg/mL)
(Revision4): XXXXXXXX
3 / 4
3.2.P.5.2 試験方法(XXX) 3 / 4
Analytical Test Procedure for Clofarabine Drug Product
(1mg/mL (Revision 4): XXXXXXXX
3 / 4
UV ID Test for Clofarabine Drug Product Release Testing:
XXXXXXXX
3 / 4
UV-Visible Spectrophotometric Identification of
Clofarabine Injection,
3 / 4
Assay and Impurities for Clofarabine Drug Product
(1mg/mL) for GENZYME Corporation: TP:66061
3 / 4
3.2.P.5.3 試験方法のバリデーション 3 / 4
Protocol: Method Validation of Clofarabine API and Clofarabine Drug
Product by High Performance Liquid Chromatography-Revision 4:
07TRSA144
3 / 4
Protocol Amendment: Method Validation of Clofarabine API and Clofarabine
Drug Product by High Performance Liquid Chromatography-Revision 4:
07TRSA144
3 / 4
Method Validation of Clofarabine API and Clofarabine Drug Product by
High Performance Liquid Chromatography-Revision 4: 07TRSA144
3 / 4
Protocol : Determination of the XXXXXXXX XXXXXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level using
High Performance Liquid Chromatography
3 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 13
巻/巻数
Project No. 6074-5124 XXXXXXXX
Protocol Amendment: Determination of the XXXXXXXX XXXXXXXX
for Clofarabine Degradation Impurities at the Limit of Quantification (LOQ)
Level using High Performance Liquid Chromatography
Project No. 6074-5124 XXXXXXXX
3 / 4
Determination of XXXXXXXX XXXXXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103
3 / 4
Addendum to Determination of the XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103 (Addendum 01)
3 / 4
Addendum to Determination of the XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification (LOQ) Level Using
High Performance Liquid Chromatography: 07TRSA103 (Addendum 02)
3 / 4
Validation Protocol of Clofarabine Process Impurities for Test Methods
XXXXXXX and XXXXXXX: 08TRSA010
3 / 4
Method Validation of Clofarabine Process Impurities for Test Methods
XXXXXXX and XXXXXXX: 08TRSA010
3 / 4
Qualification of the Analytical Method XXXXXXX for UV-Visible
Spectrophotometric Identification of Clofarabine Injection 1mg/mL
BIEN5000A1
3 / 4
エボルトラの純度試験 HPLC 法のシステム適合性(検出の確認)の検
討: IDCAD-12-025 試験報告書/試験計画書
3 / 4
3.2.P.5.3 試験方法のバリデーション(XXXX) 3 / 4
Protocol: Method Validation of Clofarabine API and
Clofarabine Drug Product by High Performance Liquid
Chromatography-Revision4: 07TRSA144
3 / 4
Protocol Amendment: Method Validation of Clofarabine
API and Clofarabine Drug Product by High Performance
Liquid Chromatography-Revision4: 07TRSA144
3 / 4
Method Validation of Clofarabine API and Clofarabine
Drug Product by High Performance Liquid
Chromatography-Revision4: 07TRSA144
3 / 4
Protocol : Determination of the XXXXXXXX XXXX
for Clofarabine Degradation Impurities at the Limit of
3 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 14
巻/巻数
Quantification (LOQ) Level using High Performance
Liquid Chromatography
Project No. 6074-5124 XXXXXXXX XXXX
Protocol Amendment: Determination of the XXXXXXX X
XX XXX for Clofarabine Degradation Impurities at the
Limit of Quantification (LOQ) Level using High
Performance Liquid Chromatography: Project No. 6074-
5124 XXXXXXXX XXXX
3 / 4
Determination of XXXXXXXX XXXX for Clofarabine
Degradation Impurities at the Limit of Quantification
(LOQ) Level Using High Performance Liquid
Chromatography: 07TRSA103
3 / 4
Addendum to Determination of the XXXXXXXX XXX
for Clofarabine Degradation Impurities at the Limit of
Quantification (LOQ) Level Using High Performance
Liquid Chromatography: 07TRSA103 (Addendum 01)
3 / 4
Addendum to Determination of the XXXXXXX XXXX
for Clofarabine Degradation Impurities at the Limit of
Quantification (LOQ) Level Using High Performance
Liquid Chromatography: 07TRSA103 (Addendum 02)
3 / 4
Validation Protocol of Clofarabine Process Impurities for
Test Methods XXXXXXX and XXXXXXX: 08TRSA010
3 / 4
Method Validation of Clofarabine Process Impurities for
Test Methods XXXXXXX and XXXXXXX: 08TRSA010
3 / 4
Qualification of the Analytical Method XXXXXXX for
UV-Visible Spectrophotometric Identification of
Clofarabine Injection 1mg/mL BIEN5000A1
3 / 4
METHOD DEVELOPMENT AND VALIDATION OF
STERILITY TEST: ILEX3003A
3 / 4
Method Development and Validation of USP Bacterial
Endotoxins (LAL) Test for Clofarabine Injection: 2524-
AMF72-ILEX
3 / 4
METHOD DEVELOPMENT AND VALIDATION OF
BIOBURDEN TEST: ILEX3002D
3 / 4
Qualification of the Analytical Method XXXXXXX for UV 3 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 15
巻/巻数
Assay of Clofarabine in Clofarabine Injection (1mg/mL):
ILEX3006
3.2.P.5.4 ロット分析 4 / 4
CERTIFICATE OF ANALYSIS Batch/lot number: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch/lot number: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch/lot number: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch/lot number: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS LOT #: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS Batch ID: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS LOT#: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS LOT#: XXXXXXX 4 / 4
CERTIFICATE OF ANALYSIS LOT#: XXXXXXX 4 / 4
3.2.P.5.4 ロット分析(XXXX) 4 / 4
Certificate of Analysis Lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
Certificate of Analysis Batch/lot#: XXXXXXX 4 / 4
3.2.P.5.5 不純物の特性 4 / 4
3.2.P.5.5 不純物の特性(XXXX) 4 / 4
3.2.P.5.6 規格及び試験方法の妥当性 4 / 4
3.2.P.5.6 規格及び試験方法の妥当性(XXXX) 4 / 4
Analytical Test Procedure for Clofarabine Drug Product (1
mg/mL) TM19.031
4 / 4
3.2.P.6 標準品または標準物質 4 / 4
3.2.P.7 容器及び施栓系 4 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 16
巻/巻数
ANALYTICAL PROCEDURE QUALITY CONTROL SNAP CAPS 4 / 4
XXXX FLIP OFF SEAL XXXX XXXXX DRAWING: NO. XXXX XXXX 4 / 4
Flip Off Seal XXXXXXXXX 4 / 4
XXXXXXXX STOPPER DRAWING: NO. XXXX X 4 / 4
XXXXXXXXXXXXXXXXXXXXXXXXXXXX 4 / 4
STANDARD OPERATING PROCEDURE – INSTRUCTION: Rubber
Stoppers
4 / 4
Injection vial XXXX Drawing number XXXXXXXX 4 / 4
STANDARD OPERATING PROCEDURE – INSTRUCTION: Injection
vials, type XXXXXXXX
4 / 4
CERTIFICATE 4 / 4
XXXXXXXX clear, Technical Data 4 / 4
Certificate of Conformity 4 / 4
3.2.P.7 容器及び施栓系(XXXX) 4 / 4
XXXX FLIP OFF SEAL XXXX XXXXX DRAWING:
NO. XXXXXXXX
4 / 4
XXXX PURFORM VIAL SERUM / LYOPHILIZATION
XXXX XXXX
4 / 4
Packaging Component Specification Vial:20mL, XXXX
Type 1 Glass (XXXX Product #6800321): PC-3196-03
4 / 4
Packaging Component Specification XXXX Flip-Off
XXXXXXXXXXXX Seal: PC-3201-01
4 / 4
Packaging Component Specification XXXXXXXX NP
Stopper, XXXX XXXX (Product ID #10144257): PC-
3274-00
4 / 4
Packaging Component Specification Label: Vial for
ClolarTM Clofarabin (1mg/mL) 20cc- Genzyme Oncology:
PC-3554-01
4 / 4
Packaging Component Specification Stopper: XXXXXXX
XXXXXXXX XXXX XXXX (Item # XXXX XXXX):
XXXXXXXX
4 / 4
XXXXXXXX STOPPER DRAWING: NO. XXXX XXXX 4 / 4
CERTIFICATE OF ANALYSIS Master Lot # XXXX XXX 4 / 4
Additional Information About USP Type I Glass 4 / 4
XXXX XXX clear 4 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 17
巻/巻数
3.2.P.8 安定性 4 / 4
3.2.P.8.1 安定性のまとめ及び結論
4 / 4
Technical Report: Clofarabine Drug Product (1 mg/ml) Photostability Study
Report Number: 0027AD5005
4 / 4
3.2.P.8/3.2.P.8.1 安定性(XXXX)/ 安定性のまとめ及び結論
(XXXX)
4 / 4
3.2.P.8.2 承認後の安定性試験計画の作成及び実施 4 / 4
3.2.P.8.2 承認後の安定性試験計画の作成及び実施 (XXXX) 4 / 4
3.2.P.8.3 安定性データ 4 / 4
Stability Report to Evaluate the Light Sensitivity of Clofarabine Injection,
XXmg/mL, Lot No. B100713: Technical Report No.: XXXXXXXX
4 / 4
3.2.P.8.3 安定性データ(XXXX) 4 / 4
3.2.A その他 4 / 4
3.2.A.1 製造施設及び設備 4 / 4
3.2.A.2 外来性感染性物質の安全性評価 4 / 4
3.2.A.3 添加剤 4 / 4
3.2.R 各極の要求資料
3.3 参考文献 4 / 4
3.3.1 Andrzejewska M, Dzierzgowska-Szmidt A, Kazimierczuk Z. Alkaline
hydrolysis of cladribine. Pharmazie 58: 122-124 (2003)
4 / 4
3.3.2 Fresenius W, Huber JFK, Pungor E, Rechnitz GA, et al. Tables of Spectral
Data for Structure Determination of Organic Compounds
13C-NMR, 1H-NMR, IR, MS, & UV/VIS. 2nd edition Springer-Verlag, NY
1989; page C212
4 / 4
3.3.3 Montgomery JA, Shortnacy-Fowler AT, Clayton SD, et al. Synthesis and
Biologic Activity of 2´-fluoro-2-halo Derivatives of 9-β-D-
Arabinofuranosyladenine. J Med Chem 1992; 35:397-401.
4 / 4
3.3.4 Saenger W. Principles of Nucleic Acid Structure, Springer-Verlag, NY,
1983: Chapter 4 - Structures and Conformational Properties of Bases,
Furanose Sugars, and Phosphate Groups.
4 / 4
3.3.5 Saenger W, Principles of Nucleic Acid Structure, Springer-Verlag, New York, 1984: Chapter 5- Physical Properties of Nucleotides: Charge Densities, pK values, Spectra, and Tautomerism
4 / 4
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 19
第 4部(モジュール 4)の目次
巻/巻数
4 第 4部(モジュール 4) 非臨床試験報告書 1 - 7/ 7
4.1 目次 1 / 7
4.2 試験報告書 1 - 6 / 7
4.2.1 薬理試験 1 / 7
4.2.1.1 効力を裏付ける試験 1 / 7
4.2.1.1.1 Genz0503-01 1 / 7
Antiproliferation, cytokine secretion, hydrogen peroxide generation, and
phagocytosis in MOLT-4 tumor, U937 cells and normal peripheral leukocytes
4.2.1.1.2 0303RX34-1 1 / 7
National Cancer Institute Developmental Therapeutics program
In-Vitro Testing Results
4.2.1.1.3 ILEX 14 1 / 7
RESPONSE OF SC CCRF-CEM LEUKEMIA TO TREATMENT WITH
ARA-C AND CLOFARABINE
4.2.1.1.4 ILEX 12 1 / 7
RESPONSE OF SC CCRF-CEM LEUKEMIA TO TREATMENT WITH
CLOFARABINE AND ARA-C
4.2.1.1.5 GZ-14 1 / 7
RESPONSE TO SUBCUTANEOUSLY IMPLANTED RL HUMAN
LYMPHOMA TO COMBINATION TREATMENT WITH CLOFARABINE
AND RITUXAN
4.2.1.1.6 ILEX 16 1 / 7
RESPONSE OF SC NCI-H460 LUNG TUMOR TO TREATMENT WITH
CLOFARABINE
4.2.1.1.7 ILEX 27 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO TREATMENT WITH
CLOFARABINE OR CPT-11
4.2.1.1.8 DE111802 02 1 / 7
CLOFARABINE DOSED PO OR IP AGINST HT29 HUMAN
COLORECTAL CARCINOMA XENOGERAFT MODEL
4.2.1.1.9 ILEX 11 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO TREATMENT WITH
CLOFARABINE
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 20
巻/巻数
4.2.1.1.10 ILEX 24 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO COMBINATION
TREATMENT WITH OXALIPLATINE AND CLOFARABINE
4.2.1.1.11 ILEX 8 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO COMBINATION
TREATMENT WITH CLOFARABINE AND 5-FU
4.2.1.1.12 ILEX 4 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO COMBINATION
TREATMENT WITH CLOFARABINE AND IRINOTECAN
4.2.1.1.13 ILEX 19 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO COMBINATION
TREATMENT WITH CLOFARABINE AND IRINOTECAN
4.2.1.1.14 ILEX 25 1 / 7
RESPONSE OF SC HT29 COLON TUMOR TO COMBINATION
TREATMENT WITH CLOFARABINE AND CAMPTOSAR
4.2.1.1.15 5260-7#138 1 / 7
RESPONSE OF SC PC-3 PROSTATE TUMOR TO TREATMENT WITH
2-CL-2’-F-ARA-A (MSC 606869) AND 2-F-ARA-AMP (MSC 312887)
4.2.1.1.16 ILEX 9 1 / 7
RESPONSE OF SC PC-3 PROSTATE TUMOR TO COMBINATION
TREATMENT WITH CLOFARABINE AND TAXOTERE
4.2.1.2 副次的薬理試験 1 / 7
4.2.1.2.1 Cerep Study 7417 1 / 7
In Vitro Pharmacology Study of compounds 144-116-10 CLO and 144-127-28-CMP
4.2.1.3 安全性薬理試験 1 / 7
4.2.1.3.1 05.059/2 1 / 7
EVALUATION OF CLOFARABINE IN THE IRWIN TEST IN THE RAT
(I.V. ADMINISTRATION SLOW BOLUS)
4.2.1.3.2 05.060/3 1 / 7
SAFETY PHARMACOLOGY STUDY ON RESPIRATORY FUNCTION
FOR CLOFARABINE IN THE RAT (WHOLE BODY
PLETHYSMOGRAPHY)
4.2.1.3.3 05.061/2 1 / 7
EVALUATION OF CLOFARABINE ON DIURESIS AND URINARY
ELECTROLYTE EXCRETION AFTER INTRAVENOUS
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 21
巻/巻数
ADMINISTRATION (SLOW BOLUS) IN THE RAT
4.2.1.3.4 MBU00028-04-1071 1 / 7
A STUDY TO ASSESS THE CARDIOVASCULAR EFFECTS OF
CLOFARABINE FOLLOWING REPEAT INTRAVENOUS
ADMINISTRATION IN TELEMETERD FISCHER 344 RATS
4.2.1.3.5 05.062/3 1 / 7
IN-VITRO EFFECT OF CLOFARABINE ON hERG CURRENT (IKr)
EXPRESSED IN HUMAN EMBRYONIC KIDNEY (HEK) CELLS
4.2.1.4 薬力学的薬物相互作用試験
4.2.2 薬物動態試験 2 / 7
4.2.2.1 分析法及びバリデーション報告書 2 / 7
4.2.2.1.1 BIOV111_003a.Bioenvision 3 2 / 7
Method for the quantitation of clofartabine in dosing solutions
4.2.2.1.2 AU211 2 / 7
THE VALIDATION OF AN HPLC/MS ASSAY TO MEASURE
CLOFARABINE IN RAT PLASMA
4.2.2.1.3 AU214 2 / 7
The application of an HPLC/MS assay to measure clofarabine in rat plasma
Study: 05.060.3
4.2.2.1.4 MC02113 2 / 7
Validation of a Method for the Determination of Clofarabine in Rat Plasma
using High Performance Liquid Chromatography with Mass Spectrometric
(MS/MS) Detection
4.2.2.1.5 MC02114 2 / 7
Validation of a Method for the Determination of Clofarabine in Dog Plasma
using High Performance Liquid Chromatography with Mass Spectrometric
(MS/MS) Detection
4.2.2.2 吸収 2 / 7
4.2.2.2.1 MC02410 2 / 7
Intravenous and Oral Pharmacokinetic Study of Clofarabine in Male CD-1
Mice
4.2.2.3 分布 2 / 7
4.2.2.3.1 QKAN-2002-0783-ADM 2 / 7
Tissue Distribution in Male Fischer 344 Rats Following a Five Day
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 22
巻/巻数
Intravenous Dose Regimen of 14C-Clofarabine
4.2.2.3.2 DMPK12-R056 2 / 7
Determination of Red Blood Cell Partitioning of Clofarabine in Human
Whole Blood
4.2.2.3.3 DMPK12-R055 2 / 7
Protein Binding of Clofarabine in Human Plasma Using Rapid Equilibrium
Dialysis
4.2.2.4 代謝 2 / 7
4.2.2.4.1 QKAN-2002-0642-BIO 2 / 7
In Vivo Metabolism of Clofarabine in Rat Myocardium, Liver, Urine, Feces
and Plasma Samples Collected from Protocol (PK-917)
4.2.2.4.2 QKAN-2002-0542-BIO 2 / 7
In Vitro Metabolism of Clofarabine in Rat, Dog and Human Cryopreserved
Hepatocytes
4.2.2.4.3 13558-103 2 / 7
Clofarabine: in Vitro Metabolic Stability in Liver Microsomes
4.2.2.4.4 DMPK12-R009 2 / 7
In Vitro Metabolism of Clofarabine by Recombinant Human Adenosine
Deaminase
4.2.2.4.5 DMPK12-R022 2 / 7
In Vitro Metabolism of Clofarabine in Recombinant Human Monoamine
Oxidase A and Monoamine Oxidase B Enzymes
4.2.2.5 排泄 2 / 7
4.2.2.5.1 QKAN-2002-0705-ADM 2 / 7
Radiokinetic and 14C Excretion/Mass Balance Study of 14C-Clofarabine in
Fischer 344 Rats.
4.2.2.5.2 Traft/15Aug07 2 / 7
Clofarabine Excretion in the Perfused Rat Kidney
4.2.2.6 薬物動態学的薬物相互作用(非臨床) 2 / 7
4.2.2.6.1 13558-109 2 / 7
Inhibition Study of Human Cytochrome P450 Isozyme catalytic activities by
Clofarabine Using Human Liver Microsomes.
4.2.2.6.2 14060-033 2 / 7
In Vitro Cytochrome P450 Profile for Clofarabine Using Fluorescent Probe
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 23
巻/巻数
Substrates.
4.2.2.6.3 5GENZP2 2 / 7
CYP INDUCTION ASSESSMENT - In vitro study to assess the potential
inducing effect of clofarabine on the activity of CYP1A2 and CYP3A4 in
human hepatocytes.
4.2.2.7 その他の薬物動態試験
4.2.3 毒性試験 2-6 / 7
4.2.3.1 単回投与毒性試験 2 / 7
4.2.3.1.1 MDACC1 2 / 7
Clofarabine Mouse Studies
4.2.3.2 反復投与毒性試験 2-4 / 7
4.2.3.2.1 0106-01 2 / 7
Five-Day Intravenous GLP Toxicity Study of Clofarabine in Male Fischer
344 Rats
4.2.3.2.2 0110-02 2 / 7
Five-Day Intravenous Infusion GLP Toxicity Study of Clofarabine in Male
Fischer 344 Rats
4.2.3.2.3 0204-03、MC02116(トキシコキネティクス) 3 / 7
CLOFARABINE: A MULTI-CYCLE (FIVE DAYS’ DOSING PLUS 23
DAYS’ RECOVERY PER CYCLE) INTRAVENOUS TOXICITY AND
TOXICOKINETICS STUDY IN FISCHER 344 RATS
4.2.3.2.4 0204-05 3 / 7
THREE WEEKLY ORAL AND INTRAVENOUS DOSE BRIDGING
TOXICITY STUDY OF CLOFARABINE IN FISCHER 344 RATS
4.2.3.2.5 0203-01、MC02111及び MC02111-A1(トキシコキネティクス) 4 / 7
CLOFARABINE: A MULTI-CYCLE (FIVE DAYS’ DOSING PLUS 23
DAYS’ RECOVERY PER CYCLE) INTRAVENOUS TOXICITY AND
TOXICOKINETICS STUDY IN BEAGLE DOGS
4.2.3.2.6 MDACC2 4 / 7
Clofarabine Dog Studies
4.2.3.2.7 0111-01 4 / 7
Five-Day Intravenous Infusion Range-Finding Study of Clofarabine in Beagle
Dogs
4.2.3.3 遺伝毒性試験 5 / 7
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 24
巻/巻数
4.2.3.3.1 In vitro 試験 5 / 7
4.2.3.3.1.1 CLO.00.07.02 5 / 7
Bacterial Reverse Mutation Assay
4.2.3.3.1.2 CLO.00.07.03 5 / 7
IN VITRO MAMMALIAN CHROMOSOME ABERRATION TEST
4.2.3.3.2 In vivo 試験 5 / 7
4.2.3.3.2.1 CLO.00.48 5 / 7
MAMMALIAN ERYTHYROCYTE MICRONUCLEUS TEST
4.2.3.4 がん原性試験
4.2.3.5 生殖発生毒性試験 5 / 7
4.2.3.5.1 受胎能及び着床までの初期胚発生に関する試験
4.2.3.5.2 胚・胎児発生に関する試験 5 / 7
4.2.3.5.2.1 0202-01 5 / 7
INTRAVENOUS DOSE-RANGE DEVELOPMENT TOXICITY STUDY
OF CLOFARABINE IN RATS
4.2.3.5.2.2 0204-01 5 / 7
INTRAVENOUS DEVELOPMENT TOXICITY STUDY OF
CLOFARABINE IN RATS
4.2.3.5.2.3 0202-02 5 / 7
INTRAVENOUS DOSE-RANGE DEVELOPMENT TOXICITY STUDY
OF CLOFARABINE IN RABBITS
4.2.3.5.2.4 0204-02 5 / 7
INTRAVENOUS DEVELOPMENT TOXICITY STUDY OF
CLOFARABINE IN RABBITS
4.2.3.5.3 出生前及び出生後の発生並びに母体の機能に関する試験
4.2.3.5.4 新生児を用いた試験
4.2.3.6 局所刺激性試験 5 / 7
4.2.3.6.1 MBU00008 5 / 7
A PRIMARY EYE IRRITATION STUDY IN RABBITS WITH
CLOFARABINE (RAW POWDER)
4.2.3.6.2 MBU00010 5 / 7
A PRIMARY EYE IRRITATION STUDY IN RABBITS WITH
CLOFARABINE (CLINICAL FORMULATION)
4.2.3.6.3 MBU00009 5 / 7
A PRIMARY SKIN IRRITATION STUDY IN RABBITS WITH
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 25
巻/巻数
CLOFARABINE (RAW POWDER)
4.2.3.6.4 MBU00011 5 / 7
A PRIMARY SKIN IRRITATION STUDY IN RABBITS WITH
CLOFARABINE (CLINICAL FORMULATION)
4.2.3.7 その他の毒性試験 6 / 7
4.2.3.7.1 抗原性試験
4.2.3.7.2 免疫毒性試験
4.2.3.7.3 毒性発現の機序に関する試験 6 / 7
4.2.3.7.3.1 0204-04 6 / 7
Five-Day Intravenous GLP Cardiac Biomarker Study of Clofarabine in Male
Fischer 344 Rats
4.2.3.7.4 依存性試験
4.2.3.7.5 代謝物の毒性試験
4.2.3.7.6 不純物の毒性試験 6 / 7
4.2.3.7.6.1 3569.4 6 / 7
A 5-DAY INTRAVENOUS TOXICITY STUDY IN FEMALE FISCHER
344 RATS COMPARING TWO LOTS OF CLOFARABINE
4.2.3.7.6.2 GT-237-TX-1 6 / 7
A 5-DAY INTRAVENOUS TOXICITY STUDY IN FEMALE FISCHER
344 RATS COMPARING TWO LOTS OF CLOFARABINE
4.2.3.7.6.3 GT-237-TX-2 6 / 7
A 5-Day Toxicity Study Comparing Clofarabine to Two Lots of Clofarabine
Containing Degradants 9 and 12 Administered Intravenously to Fischer 344
Rats
4.2.3.7.7 その他の試験 6 / 7
4.2.3.7.7.1 0658-07156 6 / 7
A FIVE DAY INTRAVENOUS, A FIVE DAY ORAL, AND A 21-DAY
ORAL COMPARATIVE HEMATOLOGICAL TOXICITY STUDY OF
CLOFARABINE IN MALE FISCHER 344 RATS
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巻/巻数
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エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
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第 5部(モジュール 5)の目次
巻/巻数
5 第 5部(モジュール 5) 臨床試験報告書 1 - 25 / 25
5.1 目次 1 / 25
5.2 臨床試験一覧表 1 / 25
5.3 試験報告書及び関連情報 1 - 24 / 25
5.3.1 生物薬剤学試験報告書 1 / 25
5.3.1.1 バイオアベイラビリティ(BA)試験報告書
5.3.1.2 比較 BA試験及び生物学的同等性試験(BE)試験報告書
5.3.1.3 In Vitro-In Vivoの関連を検討した試験報告書
5.3.1.4 生物学的及び理化学的分析法検討報告書 1 / 25
5.3.1.4.1 MC06123
Method Validation Report
Validation of a Method for the Determination of Clofarabine and 6-
Ketoclofarabine in Human Plasma using High-Performance Liquid
Chromatography with Mass Spectrometric (MS/MS) Detection
1 / 25
5.3.1.4.2 MC02298
Method Validation Report
Validation of a Method for the Determination of Clofarabine in Human
Urine using High-Performance Liquid Chromatography with Mass
Spectrometric (MS/MS) Detection
1 / 25
5.3.1.4.3 MC02293
Qualification Report
Qualification of Minor Modifications to the Method for the Determination
of Clofarabine in Human Plasma using High-Performance Liquid
Chromatography with Mass Spectrometric (MS/MS) Detection
1 / 25
5.3.1.4.4 MC02017
Method Validation Report
Validation of a Method for the Determination of Clofarabine in Human
Plasma using High-Performance Liquid Chromatography with Mass
Spectrometric (MS/MS) Detection
1 / 25
5.3.1.4.5 MC03065
Qualification Report
Qualification of Minor Modifications to the Method for the Determination
of Clofarabine in Human Plasma using High-Performance Liquid
Chromatography with Mass Spectrometric (MS/MS) Detection
1 / 25
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 33
巻/巻数
5.3.1.4.6 MC05432
Method Validation Report
Validation of a Method for the Determination of Clofarabine and 6-
Ketoclofarabine in Human Plasma using High-Performance Liquid
Chromatography with Mass Spectrometric (MS/MS) Detection
1 / 25
5.3.1.4.7 MC03171
Stability Report
Evaluation of the Frozen Stability of Clofarabine in Human Plasma using
High-Performance Liquid Chromatography with Mass Spectrometric
(MS/MS) Detection
1 / 25
5.3.1.4.8 MC03105
Stability Report
Evaluation of the Frozen Stability of Clofarabine in Human Urine using
High-Performance Liquid Chromatography with Mass Spectrometric
(MS/MS) Detection
1 / 25
5.3.2 ヒト生体試料を用いた薬物動態関連の試験報告書
5.3.3 臨床薬物動態(PK)試験報告書 1 -2 / 25
5.3.3.2 患者における PK 及び初期忍容性試験報告書 1 -2 / 25
5.3.3.2.1 Population Pharmacokinetic Analysis of Clofarabine in Adult Patients with
Advanced Solid Tumors Enrolled in Study CLO-151
1 / 25
5.3.3.2.2 Pharmacokinetic Analysis Report – CLO-152 and CLO-151 (Interim)
Pharmacokinetic Analysis of Patients Enrolled in Study CLO-152
(A Phase I, Dose Escalation and Pharmacokinetic Study of Oral
Clofarabine Administered Daily for 5 Days in Adult Patients with
Refractory Solid Tumors) And
Interim Pharmacokinetic Analysis of Patients Enrolled in Study CLO-151
(A Phase I and Pharmacokinetic Study of Clofarabine in Adult Patients
with Advanced Solid Tumors)
1 / 25
5.3.3.5 ポピュレーション PK 試験報告書 1 -2 / 25
5.3.3.5.1 FINAL Pharmacokinetic Report
Population Pharmacokinetics and Pharmacodynamics of Plasma
Clofarabine and Intracellular Clofarabine Triphosphate in Pediatric Patients
with Refractory or Relapsed Acute Lymphoblastic Leukemia or Acute
Myelogenous Leukemia
1 / 25
5.3.3.5.2 Pooled Population Pharmacokinetic Model of Clofarabine 2 / 25
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 34
巻/巻数
Erratum #1: Pooled Population Pharmacokinetic Model of Clofarabine
5.3.4 臨床薬力学(PD)試験報告書
5.3.5 有効性及び安全性試験報告書 2 / 25
5.3.5.1 申請する適応症に関する比較対照試験報告書
5.3.5.2 非対照試験報告書 2 – 10 / 25
5.3.5.2.1 CLO05908 2 / 25
PHASE 1 FINAL CLINICAL STUDY REPORT
Clofarabine
A Phase 1, Open-label, Multi-center Study of Clofarabine in Japanese
Pediatric Patients with Relapsed or Refractory Acute Lymphoblastic
Leukemia
5.3.5.2.2 ID99-383 2/ 25
Clinical Report – Protocol ID99-383
Phase I Study of CL-F-Ara-A (Clofarabine) in Pediatric Patients with
Hematologic Malignancies
5.3.5.2.3 CLO-212 3 / 25
Final Clinical Study Report – Protocol CLO-212
A Phase II, Open-Label Study of Clofarabine in Pediatric Patients with
Refractory or Relapsed Acute Lymphoblastic Leukemia
Erratum #1: Final Clinical Study Report – Protocol CLO-212
Erratum #1: Final Clinical Study Report and Addendum –Protocol CLO-
212
Addendum to CLO-212 Clinical Study Report
Final Clinical Study Report – Protocol CLO-212
5.3.5.2.4 CLO-222 3 / 25
Final Clinical Study Report – Protocol CLO-222
A Phase II, Open-Label Study of Clofarabine in Pediatric Patients With
Refractory or Relapsed Acute Myelogenous Leukemia
Erratum #1: Final Clinical Study Report – Protocol CLO-222
Erratum #1: Final Clinical Study Report – Protocol CLO-222
Addendum to CLO-222 Clinical Study Report
Final Clinical Study Report – Protocol CLO-222
5.3.5.2.5 BIOV-111 4 / 25
CLINICAL STUDY REPORT
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 35
巻/巻数
A phase II, open-label study of clofarabine in paediatric patients with
refractory / relapsed acute lymphoblastic leukaemia
Erratum #1: Final Clinical Study Report – Protocol BIOV-111
Erratum #2: Final Clinical Study Report – Protocol BIOV-111
Erratum #3: Final Clinical Study Report – Protocol BIOV-111
5.3.5.2.6 CLOAML10508 5 / 25
PHASE 1 FINAL CLINICAL STUDY REPORT
Clofarabine (Evoltra®)
A Phase 1, Open-label, Multi-center Study of Clofarabine in Japanese
Patients with Acute Myeloid Leukemia (AML)
5.3.5.2.7 DM93-036 5 / 25
Clinical Report – Protocol DM93-036
Phase I Study of 2-chloro-2′-fluoro-Deoxy-9-β-d –
rabinofuranosyladenine (Cl-F-Ara-A; clofarabine) in Solid and
Hematologic Malignancies
5.3.5.2.8 CLO-221 6 / 25
Clinical Report – Protocol CLO-221
A Phase II, Open-Label Study of Clofarabine in Adult Patients with
Refractory or Relapsed Acute Myelogenous Leukemia
5.3.5.2.9 CLO24300606 6 – 8 / 25
Final Clinical Study Report – CLO24300606
A Phase II Study of Single Agent Clofarabine in Previously Untreated
Older Adult Patients with Acute Myelogenous Leukemia (AML) for Whom
Standard Induction Chemotherapy is Unlikely to be of Benefit
5.3.5.2.10 BIOV-121 9 / 25
A Phase II Trial of Clofarabine In Older Patients With Acute Myeloid
Leukaemia For Whom Intensive Chemotherapy Is Not Considered Suitable
BIOV-121
CLINICAL STUDY REPORT
ADDENDUM OF CLINICAL STUDY REPORT
ADDEMDUM TO BIOV -121 CLINICAL STUDY REPORT
Final Clinical Study Report – Protocol BIOV – 121
5.3.5.2.11 CLO-151 10 / 25
Final Abbreviated Clinical Study Report – CLO-151
A Phase I and Pharmacokinetic Study of Clofarabine in Adult Patients with
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 36
巻/巻数
Advanced Solid Tumor
5.3.5.2.12 CLO-152 10 / 25
PHASE I DOSE-ESCALATION AND PHARMACOKINETIC STUDY
A Phase I, Dose-Escalation and Pharmacokinetic Study of Oral Clofarabine
Administered Daily for 5 Days in Adult Patients with Refractory Solid
Tumors
5.3.5.3 複数の試験成績を合わせて解析した報告書
5.3.5.4 その他の臨床試験報告書 11 -18 / 25
5.3.5.4.1 CLO34100405 11 -18 / 25
Final Clinical Study Report – CLO34100405
A Phase III Randomized, Double-Blind, Controlled Study Comparing
Clofarabine and Cytarabine vs Cytarabine Alone in Adult Patients 55 Years
and Older with Acute Myelogenous Leukemia (AML) who have Relapsed
or are Refractory after Receiving up to Two Prior Induction Regimens
5.3.6 市販後の使用経験に関する報告書 19 -21 / 25
5.3.6.1 PSUR 1 19 / 25
Evoltra® PERIODIC SAFETY UPDATE REPORT
5.3.6.2 PSUR 2 19 / 25
Evoltra® (clofarabine) PERIODIC SAFETY UPDATE REPORT
5.3.6.3 PSUR 3 19 / 25
Evoltra@ (Clofarabine) EU/1/06/334/001-004
Periodic Safety Update Report 3
5.3.6.4 PSUR 4 19 / 25
PSUR 4: PERIODIC SAFETY UPDATE REPORT for ACTIVE
SUBSTANCE(S): Clofarabine
5.3.6.5 PSUR 5 19 / 25
Evoltra@, 1mg/m1 concentrate for solution for infusion EU/1/06/334/001-
004
Periodic Safety Report 5
5.3.6.6 PSUR 6 20 / 25
6th PERIODIC SAFETY UPDATE REPORT for Evoltra® / Clolar®
(clofarabine) 1 mg/ml concentrate for solution for infusion
5.3.6.7 PSUR 7 20 / 25
7th PERIODIC SAFETY UPDATE REPORT for Evoltra® / Clolar®
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 37
巻/巻数
(clofarabine) 1 mg/ml concentrate for solution for infusion
5.3.6.8 PSUR 8 21 / 25
8th PERIODIC SAFETY UPDATE REPORT for Evoltra® / Clolar®
(clofarabine) 1 mg/ml concentrate for solutioli for infusion
5.3.7 患者データ一覧表及び症例記録 22 -24 / 25
5.3.7.1 用量設定の根拠となった主要な試験及び主要な有効性の検証試験の
症例一覧
22 / 25
5.3.7.1.1 ID99-383 22 / 25
Listing of Individual Patient Data Summary – ID99-383
5.3.7.1.2 CLO-212 22 / 25
Listing of Individual Patient Data Summary – CLO-212
5.3.7.1.3 CLO-222 22 / 25
Listing of Individual Patient Data Summary – CLO-222
5.3.7.1.4 BIOV-111 22 / 25
Listing of Individual Patient Data Summary – BIOV-111
5.3.7.1.5 CLO05908 22 / 25
Listing of Individual Patient Data Summary – CLO05908
5.3.7.1.6 CLOAML10508 22 / 25
Listing of Individual Patient Data Summary – CLOAML10508
5.3.7.2 実施された臨床試験において副作用が観察された症例の一覧表 22 / 25
5.3.7.2.1 ID99-383 22 / 25
Listing of Adverse Reactions – ID99-383
5.3.7.2.2 CLO-212 22 / 25
Listing of Adverse Reactions – CLO-212
5.3.7.2.3 CLO-222 22 / 25
Listing of Adverse Reactions – CLO-222
5.3.7.2.4 BIOV-111 22 / 25
Listing of Adverse Reactions – BIOV-111
5.3.7.2.5 CLO05908 22 / 25
Listing of Adverse Reactions – CLO05908
5.3.7.2.6 CLOAML10508 22 / 25
Listing of Adverse Reactions – CLOAML10508
5.3.7.3 実施された臨床試験において重篤な有害事象が観察された症例の一
覧表
22 / 25
5.3.7.3.1 ID99-383 22 / 25
エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 38
巻/巻数
Listing of Serious Adverse Events – ID99-383
5.3.7.3.2 CLO-212 22 / 25
Listing of Serious Adverse Events - CLO-212
5.3.7.3.3 CLO-222 22 / 25
Listing of Serious Adverse Events – CLO-222
5.3.7.3.4 BIOV-111 22 / 25
Listing of Serious Adverse Events – BIOV-111
5.3.7.3.5 CLO05908 22 / 25
Listing of Serious Adverse Events – CLO05908
5.3.7.3.6 CLOAML10508 22 / 25
Listing of Serious Adverse Events – CLOAML10508
5.3.7.4 実施された臨床試験において臨床検査異常変動が観察された症例の
一覧表
22 - 24 / 25
5.3.7.4.1 ID99-383 22 / 25
Listing of Clinical Laboratory Abnormalities – ID99-383
5.3.7.4.2 CLO-212 23 / 25
Listing of Clinical Laboratory Abnormalities - CLO-212
5.3.7.4.3 CLO-222 24 / 25
Listing of Clinical Laboratory Abnormalities – CLO-222
5.3.7.4.4 BIOV-111 24 / 25
Listing of Clinical Laboratory Abnormalities – BIOV-111
5.3.7.4.5 CLO05908 24 / 25
Listing of Clinical Laboratory Abnormalities – CLO05908
5.3.7.4.6 CLOAML10508 24 / 25
Listing of Clinical Laboratory Abnormalities – CLOAML10508
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エボルトラ点滴静注 20mg モジュール 2.1 CTD の目次(第 2部から第 5 部)
2.1 - 39
巻/巻数
5.4.4 厚生労働省平成 20年度患者調査、閲覧第 4表、推計患者数、性 ×
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巻/巻数
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