《ICH/美國臨床試驗法規選編》是化學工業出版社出版圖書。
基本介紹
- 書名：ICH/美國臨床試驗法規選編
- 作者：陳東 主編
- ISBN：978-7-122-32884-7
- 頁數：491頁
- 出版時間：2018年11月
- 裝幀：平
- 開本：大32K 850×1168 1/32
- 版次：1版1次
內容簡介,圖書目錄,
內容簡介
本書以中英文對照的形式對ICH GCP(E6_R2)以及美國聯邦法規21CFR和45CFR有關臨床試驗相關章節進行翻譯、彙編，中英文對照方便讀者學習、查閱。本書適用於製藥企業、新藥研發機構、臨床試驗機構、CRO公司、SMO公司的從業人員，也可供相關管理部門參考。
圖書目錄
國際人用藥品註冊技術協調會（ICH）
——臨床試驗質量管理規範指導原則（E6_R2）
引言3
1術語4
2ICH GCP 的原則12
3機構審查委員會/獨立倫理委員會（IRB/IEC）14
3.1職責14
3.2組成、職責和運作15
3.3程式15
3.4記錄16
4研究者17
4.1研究者的資格和協定17
4.2足夠的資源17
4.3受試者的醫療保健18
4.4與IRB/IEC溝通18
4.5依從試驗方案18
4.6試驗用藥19
4.7隨機化程式和破盲19
4.8受試者的知情同意20
4.9記錄和報告23
4.10進展報告24
4.11安全性報告24
4.12試驗的終止或暫停24
4.13研究者的最終報告25
5申辦者25
5.0質量管理25
5.1質量保證和質量控制27
5.2契約研究組織（CRO）27
5.3醫學專家27
5.4試驗設計28
5.5試驗管理、數據處理與記錄保存28
5.6研究者的選擇30
5.7責任的分配30
5.8對受試者和研究者的補償30
5.9財務31
5.10通知/申報管理當局31
5.11IRB/IEC審評和確認31
5.12有關試驗用藥信息32
5.13試驗用藥的生產、包裝、標籤和編碼32
5.14試驗用藥的供應和管理32
5.15記錄查閱33
5.16安全性信息33
5.17藥品不良反應報告33
5.18監查34
5.19稽查38
5.20不依從38
5.21提前終止或暫停試驗39
5.22臨床試驗/研究報告39
5.23多中心試驗39
6臨床試驗方案和方案增補40
6.1一般信息40
6.2背景信息40
6.3試驗目標和目的41
6.4試驗設計41
6.5受試者的選擇和退出41
6.6受試者的治療42
6.7有效性評價42
6.8安全性評價42
6.9統計42
6.10直接查閱原始數據/檔案42
6.11質量控制和質量保證43
6.12倫理學43
6.13數據處理與記錄保存43
6.14財務和保險43
6.15出版策略43
6.16補充43
7研究者手冊43
7.1引言43
7.2總論44
7.3研究者手冊的內容44
7.4附錄149
7.5附錄250
8實施臨床試驗的核心檔案51
8.1引言51
8.2臨床試驗開始之前52
8.3臨床試驗進行期間54
8.4臨床試驗完成或終止之後57
美國聯邦法案
21CFR第11部分電子記錄/電子簽名60
子部分A總則60
——臨床試驗質量管理規範指導原則（E6_R2）
引言3
1術語4
2ICH GCP 的原則12
3機構審查委員會/獨立倫理委員會（IRB/IEC）14
3.1職責14
3.2組成、職責和運作15
3.3程式15
3.4記錄16
4研究者17
4.1研究者的資格和協定17
4.2足夠的資源17
4.3受試者的醫療保健18
4.4與IRB/IEC溝通18
4.5依從試驗方案18
4.6試驗用藥19
4.7隨機化程式和破盲19
4.8受試者的知情同意20
4.9記錄和報告23
4.10進展報告24
4.11安全性報告24
4.12試驗的終止或暫停24
4.13研究者的最終報告25
5申辦者25
5.0質量管理25
5.1質量保證和質量控制27
5.2契約研究組織（CRO）27
5.3醫學專家27
5.4試驗設計28
5.5試驗管理、數據處理與記錄保存28
5.6研究者的選擇30
5.7責任的分配30
5.8對受試者和研究者的補償30
5.9財務31
5.10通知/申報管理當局31
5.11IRB/IEC審評和確認31
5.12有關試驗用藥信息32
5.13試驗用藥的生產、包裝、標籤和編碼32
5.14試驗用藥的供應和管理32
5.15記錄查閱33
5.16安全性信息33
5.17藥品不良反應報告33
5.18監查34
5.19稽查38
5.20不依從38
5.21提前終止或暫停試驗39
5.22臨床試驗/研究報告39
5.23多中心試驗39
6臨床試驗方案和方案增補40
6.1一般信息40
6.2背景信息40
6.3試驗目標和目的41
6.4試驗設計41
6.5受試者的選擇和退出41
6.6受試者的治療42
6.7有效性評價42
6.8安全性評價42
6.9統計42
6.10直接查閱原始數據/檔案42
6.11質量控制和質量保證43
6.12倫理學43
6.13數據處理與記錄保存43
6.14財務和保險43
6.15出版策略43
6.16補充43
7研究者手冊43
7.1引言43
7.2總論44
7.3研究者手冊的內容44
7.4附錄149
7.5附錄250
8實施臨床試驗的核心檔案51
8.1引言51
8.2臨床試驗開始之前52
8.3臨床試驗進行期間54
8.4臨床試驗完成或終止之後57
美國聯邦法案
21CFR第11部分電子記錄/電子簽名60
子部分A總則60
11.1適用範圍60
11.2履行60
11.3定義61
子部分B電子記錄62
11.10封閉系統的控制62
11.30開放系統的控制63
11.50簽名顯示63
11.70簽名/記錄連結64
子部分C電子簽名64
11.100一般要求64
11.200電子簽名構成要素及管控64
11.300識別碼/密碼的管控65
21CFR第50部分保護人類受試者66
子部分A總則66
50.1範圍66
50.3定義66
子部分B人類受試者知情同意70
50.20對知情同意的一般要求70
50.23一般要求之外的例外情形70
50.24為急救研究豁免知情同意的要求75
50.25知情同意要素78
50.27記錄知情同意過程80
子部分C\[保留\]80
子部分D在臨床研究中對兒童的額外保護80
50.50IRB責任80
50.51不高於最低風險的臨床研究81
50.52涉及高於最低風險，但呈現出對受試者直接受益前景的臨床研究81
50.53臨床研究涉及高於最低風險，且對受試者沒有直接有益的前景，但可能獲得對受試者的機能失調或健康狀況的一般性知識81
50.54隻有通過進行臨床研究才有機會了解、預防或減輕影響兒童健康或福祉的嚴重問題的臨床研究82
50.55由家長或監護人代替兒童同意參加試驗的要求82
50.56受監護的兒童8321CFR第54部分臨床研究者財務公開85
54.1目的85
54.2定義85
54.3範圍86
54.4財務證明和財務公開聲明要求87
54.5FDA對財務利益的評估88
54.6保存記錄及記錄保留89
21CFR第56部分機構審查委員會90
子部分A總則90
56.101範圍90
56.102定義90
56.103需要IRB審核的情形93
56.104豁免IRB要求94
56.105免除IRB要求94
子部分B組織和人員94
56.106登記94
56.107IRB組成成員96
子部分CIRB的功能及運營97
56.108IRB的功能及運營97
56.109IRB審核研究97
56.110快速審核程式：涉及不高於最低風險及對已批准的研究進行微小變更99
56.111IRB審核研究的標準99
56.112機構審查委員會審核100
56.113暫停或終止IRB對研究的批准100
56.114合作研究100
子部分D記錄和報告101
56.115IRB記錄101
子部分E對不依從的行政處罰102
11.2履行60
11.3定義61
子部分B電子記錄62
11.10封閉系統的控制62
11.30開放系統的控制63
11.50簽名顯示63
11.70簽名/記錄連結64
子部分C電子簽名64
11.100一般要求64
11.200電子簽名構成要素及管控64
11.300識別碼/密碼的管控65
21CFR第50部分保護人類受試者66
子部分A總則66
50.1範圍66
50.3定義66
子部分B人類受試者知情同意70
50.20對知情同意的一般要求70
50.23一般要求之外的例外情形70
50.24為急救研究豁免知情同意的要求75
50.25知情同意要素78
50.27記錄知情同意過程80
子部分C\[保留\]80
子部分D在臨床研究中對兒童的額外保護80
50.50IRB責任80
50.51不高於最低風險的臨床研究81
50.52涉及高於最低風險，但呈現出對受試者直接受益前景的臨床研究81
50.53臨床研究涉及高於最低風險，且對受試者沒有直接有益的前景，但可能獲得對受試者的機能失調或健康狀況的一般性知識81
50.54隻有通過進行臨床研究才有機會了解、預防或減輕影響兒童健康或福祉的嚴重問題的臨床研究82
50.55由家長或監護人代替兒童同意參加試驗的要求82
50.56受監護的兒童8321CFR第54部分臨床研究者財務公開85
54.1目的85
54.2定義85
54.3範圍86
54.4財務證明和財務公開聲明要求87
54.5FDA對財務利益的評估88
54.6保存記錄及記錄保留89
21CFR第56部分機構審查委員會90
子部分A總則90
56.101範圍90
56.102定義90
56.103需要IRB審核的情形93
56.104豁免IRB要求94
56.105免除IRB要求94
子部分B組織和人員94
56.106登記94
56.107IRB組成成員96
子部分CIRB的功能及運營97
56.108IRB的功能及運營97
56.109IRB審核研究97
56.110快速審核程式：涉及不高於最低風險及對已批准的研究進行微小變更99
56.111IRB審核研究的標準99
56.112機構審查委員會審核100
56.113暫停或終止IRB對研究的批准100
56.114合作研究100
子部分D記錄和報告101
56.115IRB記錄101
子部分E對不依從的行政處罰102
56.120行政措施102
56.121取消IRB或研究機構的資格102
56.122公開披露撤銷信息103
56.123恢復IRB或機構103
56.124取消資格的替代措施或補充措施103
21CFR第312部分研究新藥申請104
子部分A一般條款104
312.1範圍104
312.2適用性104
312.3定義和釋義105
312.6研究新藥標籤107
312.7研究用藥的推廣107
312.8對IND下研究用藥的收費107
312.10免除要求110
子部分B研究新藥申請（IND）110
312.20對IND的要求110
312.21研究階段110
312.22提交IND的一般原則111
312.23IND內容和格式112
312.30方案增補120
312.31信息增補122
312.32IND安全性報告122
312.33年度報告126
312.38撤銷IND127
子部分C行政措施128
312.40在臨床研究中對使用研究新藥的一般要求128
312.41對IND的意見和建議128
312.42臨床研究暫停和修改要求129
312.44終止132
312.45非活動狀態134
312.47會議135
312.48解決爭議138
子部分D申辦者和研究者的責任139
312.50申辦者的一般責任139
312.52向契約研究組織(CRO）轉讓義務139
312.53選擇研究者和監查員139
312.54符合本章50.24規定的急救研究141
312.55告知研究者142
312.56審核正在進行的研究142
312.57記錄保存和記錄保留143
312.58對申辦者記錄和報告的視察143
312.59處置未使用的研究用藥144
312.60研究者的一般責任144
312.61對研究用藥的管控144
312.62研究者記錄和記錄保留144
312.64研究者報告145
312.66IRB審核的保證145
312.68對研究者記錄和報告的視察145
312.69處理受管制物質146
312.70取消臨床研究者的資格146
子部分E用於治療危及生命和嚴重衰弱疾病的藥物147
312.80目的147
312.81範圍148
312.82提早諮詢148
312.83治療方案149
312.84審核用於治療危及生命和嚴重衰弱疾患藥物上市許可申請的風險利益分析149
312.85Ⅳ期臨床研究150
312.86FDA重點監管的研究150
312.87主動監查臨床研究的實施和評估150
312.88受試者安全保護150
子部分F其他150
312.110進出口要求150
312.120不受IND監管的美國以外的臨床研究154
312.130公開披露IND數據和信息156
312.140通信地址157
312.145指南檔案158
子部分G用於實驗室動物研究和體外試驗的研究用藥158
312.160用於實驗室動物研究和體外試驗的研究用藥158
子部分H[保留]160
子部分I擴展研究用藥的治療用途160
312.300總論160
312.305對擴展研究用藥治療範圍的要求160
312.310個別患者，包括急救使用藥物者163
312.315中等規模患者人群164
312.320治療性IND或治療性方案166
21CFR第812部分研究器械豁免167
子部分A一般規定167
812.1範圍167
812.2適用性167
812.3定義169
812.5研究器械標籤171
812.7禁止宣傳和其他行為172
812.10免除要求172
812.18進出口要求173
812.19IDE通信地址173
子部分B申請和行政措施173
812.20申請173
812.25研究計畫175
812.27研究前報告176
812.30FDA對申請的行動措施176
812.35補充申請178
812.36研究器械的治療使用180
812.38數據和信息的保密183
子部分C申辦者責任184
812.40申辦者的一般責任184
812.42FDA和IRB批准185
812.43選擇研究者和監查員185
812.45告知研究者186
812.46監查研究186
812.47本章50.24監管下的急救研究186
子部分DIRB審核和批准187
812.60IRB的組成，職責和職能187
812.62IRB批准187
812.64IRB持續審核187
812.65[保留]187
812.66重大風險器械確定187
子部分E研究者的責任188
812.100研究者的一般責任188
812.110研究者的具體責任188
812.119取消臨床研究者的資格188
子部分F[保留]190
子部分G記錄和報告190
812.140記錄190
812.145視察192
812.150報告193
45CFR第46部分保護人類受試者196
子部分A保護人類受試者的基本衛生和公共服務（HHS）政策196
46.101政策適用範圍（略）196
46.102定義196
46.103確保遵守本政策——由聯邦部門或政府機構進行或支持的研究197
46.104—46.106[保留]200
46.107IRB會員資格200
46.108IRB的功能和操作201
46.109IRB審核研究201
46.110快速審核程式，涉及不高於最低風險的某些研究，以及批准研究的微小變更201
46.111IRB批准研究的標準202
46.112機構審核203
46.113暫停或終止IRB批准的研究203
46.114合作研究203
46.115IRB記錄203
46.116知情同意的一般要求204
46.117知情同意記錄206
46.118申請和提案缺乏明確的人類受試者參與計畫207
46.119無意涉及人類受試者的研究207
46.120評估和處理由聯邦部門或政府機構執行或支持的研究申請與提案207
46.121[保留]208
46.122使用聯邦資金208
46.123提前終止研究支持：評估申請和提案208
46.124條件208
子部分B涉及孕婦、胎兒和新生兒研究的額外保護208
46.201規定適用範圍？（略）208
46.202定義208
46.203IRB在涉及孕婦、胎兒和新生兒相關研究的職責209
46.204涉及孕婦或胎兒的研究209
46.205涉及新生兒的研究210
46.206研究涉及分娩後胎盤、死胎或胎兒物質211
46.207不批准研究就沒有機會進行了解、預防或減輕影響孕婦、胎兒或新生兒健康或福祉的嚴重問題212
子部分C涉及將囚犯作為受試者的生物醫學和行為研究的附加保護212
46.301適用範圍（略）212
46.302目的212
46.303定義212
46.304囚犯參與研究時機構審查委員會的組成213
46.305機構審查委員會對囚犯參與研究的附加職責213
46.306允許涉及囚犯的研究214
子部分D研究中涉及兒童作為受試者的其他保護215
46.401本規定適用範圍（略）215
46.402定義215
46.403IRB的職責215
46.404不涉及高於最低風險的研究215
46.405研究涉及的風險高於最低風險，但對受試者有直接受益的前景216
46.406研究涉及的風險大於最低風險，對個體受試者無直接受益前景，但可能獲得關於受試者的疾病或病症的一般性知識216
46.407不批准研究就沒有機會了解、預防或減輕影響兒童健康或福祉的嚴重問題216
46.408父母或監護人許可兒童參與研究的要求217
46.409受監護的兒童218
子部分E機構審查委員會的登記（略）218
ICH GUIDELINE FOR GOOD CLINICAL PRACTICE（GCP）(E6_R2)
Current Step 4 version dated 9 November 2016
Introduction221
1.Glossary222
2.The Principles of ICH GCP232
3.Institutional Review Board/Independent Ethics Committee(IRB/IEC)234
3.1Responsibilities234
3.2Composition,Functions and Operations235
3.3Procedures236
3.4Records237
4.Investigator237
4.1Investigators Qualifications and Agreements237
4.2Adequate Resources238
4.3Medical Care of Trial Subjects239
4.4Communication with IRB/IEC239
4.5Compliance with Protocol239
4.6Investigational Product(s)240
4.7Randomization Procedures and Unblinding241
4.8Informed Consent of Trial Subjects241
4.9Records and Reports246
4.10Progress Reports247
4.11Safety Reporting247
4.12Premature Termination or Suspension of a Trial248
4.13Final Report(s) by Investigator248
5.Sponsor249
5.0Quality Management249
5.1Quality Assurance and Quality Control251
5.2Contract Research Organization(CRO)251
5.3Medical Expertise251
5.4Trial Design252
5.5Trial Management,Data Handling,and Record Keeping252
5.6Investigator Selection254
5.7Allocation of Responsibilities255
5.8Compensation to Subjects and Investigators255
5.9Financing255
5.10Notification/Submission to Regulatory Authority(ies)256
5.11Confirmation of Review by IRB/IEC256
5.12Information on Investigational Product(s)256
5.13Manufacturing,Packaging,Labelling,and Coding Investigational Product(s)257
5.14Supplying and Handling Investigational Product(s)257
5.15Record Access259
5.16Safety Information259
5.17Adverse Drug Reaction Reporting259
5.18Monitoring259
5.19Audit265
5.20Noncompliance266
5.21Premature Termination or Suspension of a Trial266
5.22Clinical Trial/Study Reports266
5.23Multicentre Trials267
6.Clinical Trial Protocol and Protocol Amendment(s)267
6.1General Information267
6.2Background Information268
6.3Trial Objectives and Purpose268
6.4Trial Design268
6.5Selection and Withdrawal of Subjects269
6.6Treatment of Subjects269
6.7Assessment of Efficacy270
6.8Assessment of Safety270
6.9Statistics270
6.10Direct Access to Source Data/Documents271
6.11Quality Control and Quality Assurance271
6.12Ethics271
6.13Data Handling and Record Keeping271
6.14Financing and Insurance271
6.15Publication Policy271
6.16Supplements271
7.Investigators Brochure271
7.1Introduction271
7.2General Considerations273
7.3Contents of the Investigators Brochure273
7.4Appendix 1279
7.5Appendix 2280
8.Essential Documents for the Conduct of a Clinical Trial281
8.1Introduction281
8.2Before the Clinical Phase of the Trial Commences282
8.3During the Clinical Conduct of the Trial287
8.4After Completion or Termination of the Trial292
CODE OF FEDERAL REGULATIONS
21CFRPART11ELECTRONIC RECORDS;ELECTRONIC SIGNATURES296
Subpart A - General Provisions296
Sec.11.1Scope.296
Sec.11.2Implementation.297
Sec.11.3Definitions.297
Subpart B - Electronic Records298
Sec.11.10Controls for closed systems.298
Sec.11.30Controls for open systems.300
Sec.11.50Signature manifestations.300
Sec.11.70Signature/record linking.300
Subpart C - Electronic Signatures300
Sec.11.100General requirements.300
Sec.11.200Electronic signature components and controls.301
Sec.11.300Controls for identification codes/passwords.302
21CFRPART50PROTECTION OF HUMAN SUBJECTS303
Subpart A - General Provisions303
Sec.50.1Scope.303
Sec.50.3Definitions.303
Subpart B - Informed Consent of Human Subjects308
Sec.50.20General requirements for informed consent.308
Sec.50.23Exception from general requirements.308
Sec.50.24Exception from informed consent requirements for emergency research.314
Sec.50.25Elements of informed consent.318
Sec.50.27Documentation of informed consent.320
Subpart C [Reserved]321
5.14Supplying and Handling Investigational Product(s)257
5.15Record Access259
5.16Safety Information259
5.17Adverse Drug Reaction Reporting259
5.18Monitoring259
5.19Audit265
5.20Noncompliance266
5.21Premature Termination or Suspension of a Trial266
5.22Clinical Trial/Study Reports266
5.23Multicentre Trials267
6.Clinical Trial Protocol and Protocol Amendment(s)267
6.1General Information267
6.2Background Information268
6.3Trial Objectives and Purpose268
6.4Trial Design268
6.5Selection and Withdrawal of Subjects269
6.6Treatment of Subjects269
6.7Assessment of Efficacy270
6.8Assessment of Safety270
6.9Statistics270
6.10Direct Access to Source Data/Documents271
6.11Quality Control and Quality Assurance271
6.12Ethics271
6.13Data Handling and Record Keeping271
6.14Financing and Insurance271
6.15Publication Policy271
6.16Supplements271
7.Investigators Brochure271
7.1Introduction271
7.2General Considerations273
7.3Contents of the Investigators Brochure273
7.4Appendix 1279
7.5Appendix 2280
8.Essential Documents for the Conduct of a Clinical Trial281
8.1Introduction281
8.2Before the Clinical Phase of the Trial Commences282
8.3During the Clinical Conduct of the Trial287
8.4After Completion or Termination of the Trial292
CODE OF FEDERAL REGULATIONS
21CFRPART11ELECTRONIC RECORDS;ELECTRONIC SIGNATURES296
Subpart A - General Provisions296
Sec.11.1Scope.296
Sec.11.2Implementation.297
Sec.11.3Definitions.297
Subpart B - Electronic Records298
Sec.11.10Controls for closed systems.298
Sec.11.30Controls for open systems.300
Sec.11.50Signature manifestations.300
Sec.11.70Signature/record linking.300
Subpart C - Electronic Signatures300
Sec.11.100General requirements.300
Sec.11.200Electronic signature components and controls.301
Sec.11.300Controls for identification codes/passwords.302
21CFRPART50PROTECTION OF HUMAN SUBJECTS303
Subpart A - General Provisions303
Sec.50.1Scope.303
Sec.50.3Definitions.303
Subpart B - Informed Consent of Human Subjects308
Sec.50.20General requirements for informed consent.308
Sec.50.23Exception from general requirements.308
Sec.50.24Exception from informed consent requirements for emergency research.314
Sec.50.25Elements of informed consent.318
Sec.50.27Documentation of informed consent.320
Subpart C [Reserved]321
Subpart D - Additional Safeguards for Children in Clinical Investigations321
Sec.50.50IRB duties.321
Sec.50.51Clinical investigations not involving greater than minimal risk.321
Sec.50.52Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.321
Sec.50.53Clinical investigations involving greater than minimal risk and no prospect of direct benefit to individual subjects,but likely to yield generalizable knowledge about the subjects disorder or ondition.322
Sec.50.54Clinical investigations not otherwise approvable that present an opportunity to understand, prevent,or alleviate a serious problem affecting the health or welfare of children.322
Sec.50.55Requirements for permission by parents or guardians and for assent by children.323
Sec.50.56Wards.324
21CFRPART54FINANCIAL DISCLOSURE BY CLINICAL INVESTIGATORS326Sec.54.1Purpose.326
Sec.54.2Definitions.326
Sec.54.3Scope.328
Sec.54.4Certification and disclosure requirements.328
Sec.54.5Agency evaluation of financial interests.330
Sec.54.6Recordkeeping and record retention.331
21CFRPART56INSTITUTIONAL REVIEW BOARDS332
Subpart A-General Provisions332
Sec.56.101Scope.332
Sec.56.102Definitions.332
Sec.56.103Circumstances in which IRB review is required.336
Sec.56.104Exemptions from IRB requirement.337
Sec.56.105Waiver of IRB requirement.337
Subpart B-Organization and Personnel337
Sec.56.106Registration.337
Sec.56.107IRB membership.339
Subpart C-IRB Functions and Operations340
Sec.56.108IRB functions and operations.340
Sec.56.109IRB review of research.341
Sec.56.110Expedited review procedures for certain kinds of research involving no more than minimal risk,and for minor changes in approved research.343
Sec.56.111Criteria for IRB approval of research.343
Sec.56.112Review by institution.344
Sec.56.113Suspension or termination of IRB approval of research.345
Sec.56.114Cooperative research.345
Subpart D-Records and Reports345
Sec.56.115IRB records.345
Subpart E-Administrative Actions for Noncompliance346
Sec.56.120Lesser administrative actions.346
Sec.56.121Disqualification of an IRB or an institution.347
Sec.56.122Public disclosure of information regarding revocation.348
Sec.56.123Reinstatement of an IRB or an institution.348
Sec.56.124Actions alternative or additional to disqualification.348
21CFRPART312INVESTIGATIONAL NEW DRUG APPLICATION349Subpart A-General Provisions349
Sec.312.1Scope.349
Sec.312.2Applicability.349
Sec.312.3Definitions and interpretations.351
Sec.312.6Labeling of an investigational new drug.352
Sec.312.7Promotion of investigational drugs.353
Sec.312.8Charging for investigational drugs under an IND.353
Sec.312.10Waivers.356
Subpart B-Investigational New Drug Application(IND)357
Sec.312.20Requirement for an IND.357
Sec.312.21Phases of an investigation.357
Sec.312.22General principles of the IND submission.358
Sec.312.23IND content and format.359
Sec.312.30Protocol amendments.369
Sec.312.31Information amendments.371
Sec.312.32IND safety reporting.372
Sec.312.33Annual reports.377
Sec.312.38Withdrawal of an IND.378
Subpart C-Administrative Actions379
Sec.312.40General requirements for use of an investigationalnew drug in a clinical investigation.379
Sec.312.41Comment and advice on an IND.379
Sec.312.42Clinical holds and requests for modification.380
Sec.312.44Termination.384
Sec.312.45Inactive status.387
Sec.312.47Meetings.388
Sec.312.48Dispute resolution.391
Subpart D-Responsibilities of Sponsors and Investigators392
Sec.312.50General responsibilities of sponsors.392
Sec.312.52Transfer of obligations to a contract researchorganization.392
Sec.312.53Selecting investigators and monitors.393
Sec.312.54Emergency research under 50.24 of this chapter.395
Sec.312.55Informing investigators.396
Sec.312.56Review of ongoing investigations.396
Sec.312.57Recordkeeping and record retention.397
Sec.312.58Inspection of sponsors records and reports.397
Sec.312.59Disposition of unused supply ofinvestigational drug.398
Sec.312.60General responsibilities of investigators.398
Sec.312.61Control of the investigational drug.399
Sec.312.62Investigator recordkeeping and record retention.399
Sec.312.64Investigator reports.399
Sec.312.66Assurance of IRB review.400
Sec.312.68Inspection of investigator's records and reports.400
Sec.312.69Handling of controlled substances.401
Sec.312.70Disqualification of a clinical investigator.401
Subpart E-Drugs Intended to Treat Life-threatening and Severely-debilitating Illnesses403
Sec.312.80Purpose.403
Sec.312.81Scope.403
Sec.312.82Early consultation.404
Sec.50.50IRB duties.321
Sec.50.51Clinical investigations not involving greater than minimal risk.321
Sec.50.52Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.321
Sec.50.53Clinical investigations involving greater than minimal risk and no prospect of direct benefit to individual subjects,but likely to yield generalizable knowledge about the subjects disorder or ondition.322
Sec.50.54Clinical investigations not otherwise approvable that present an opportunity to understand, prevent,or alleviate a serious problem affecting the health or welfare of children.322
Sec.50.55Requirements for permission by parents or guardians and for assent by children.323
Sec.50.56Wards.324
21CFRPART54FINANCIAL DISCLOSURE BY CLINICAL INVESTIGATORS326Sec.54.1Purpose.326
Sec.54.2Definitions.326
Sec.54.3Scope.328
Sec.54.4Certification and disclosure requirements.328
Sec.54.5Agency evaluation of financial interests.330
Sec.54.6Recordkeeping and record retention.331
21CFRPART56INSTITUTIONAL REVIEW BOARDS332
Subpart A-General Provisions332
Sec.56.101Scope.332
Sec.56.102Definitions.332
Sec.56.103Circumstances in which IRB review is required.336
Sec.56.104Exemptions from IRB requirement.337
Sec.56.105Waiver of IRB requirement.337
Subpart B-Organization and Personnel337
Sec.56.106Registration.337
Sec.56.107IRB membership.339
Subpart C-IRB Functions and Operations340
Sec.56.108IRB functions and operations.340
Sec.56.109IRB review of research.341
Sec.56.110Expedited review procedures for certain kinds of research involving no more than minimal risk,and for minor changes in approved research.343
Sec.56.111Criteria for IRB approval of research.343
Sec.56.112Review by institution.344
Sec.56.113Suspension or termination of IRB approval of research.345
Sec.56.114Cooperative research.345
Subpart D-Records and Reports345
Sec.56.115IRB records.345
Subpart E-Administrative Actions for Noncompliance346
Sec.56.120Lesser administrative actions.346
Sec.56.121Disqualification of an IRB or an institution.347
Sec.56.122Public disclosure of information regarding revocation.348
Sec.56.123Reinstatement of an IRB or an institution.348
Sec.56.124Actions alternative or additional to disqualification.348
21CFRPART312INVESTIGATIONAL NEW DRUG APPLICATION349Subpart A-General Provisions349
Sec.312.1Scope.349
Sec.312.2Applicability.349
Sec.312.3Definitions and interpretations.351
Sec.312.6Labeling of an investigational new drug.352
Sec.312.7Promotion of investigational drugs.353
Sec.312.8Charging for investigational drugs under an IND.353
Sec.312.10Waivers.356
Subpart B-Investigational New Drug Application(IND)357
Sec.312.20Requirement for an IND.357
Sec.312.21Phases of an investigation.357
Sec.312.22General principles of the IND submission.358
Sec.312.23IND content and format.359
Sec.312.30Protocol amendments.369
Sec.312.31Information amendments.371
Sec.312.32IND safety reporting.372
Sec.312.33Annual reports.377
Sec.312.38Withdrawal of an IND.378
Subpart C-Administrative Actions379
Sec.312.40General requirements for use of an investigationalnew drug in a clinical investigation.379
Sec.312.41Comment and advice on an IND.379
Sec.312.42Clinical holds and requests for modification.380
Sec.312.44Termination.384
Sec.312.45Inactive status.387
Sec.312.47Meetings.388
Sec.312.48Dispute resolution.391
Subpart D-Responsibilities of Sponsors and Investigators392
Sec.312.50General responsibilities of sponsors.392
Sec.312.52Transfer of obligations to a contract researchorganization.392
Sec.312.53Selecting investigators and monitors.393
Sec.312.54Emergency research under 50.24 of this chapter.395
Sec.312.55Informing investigators.396
Sec.312.56Review of ongoing investigations.396
Sec.312.57Recordkeeping and record retention.397
Sec.312.58Inspection of sponsors records and reports.397
Sec.312.59Disposition of unused supply ofinvestigational drug.398
Sec.312.60General responsibilities of investigators.398
Sec.312.61Control of the investigational drug.399
Sec.312.62Investigator recordkeeping and record retention.399
Sec.312.64Investigator reports.399
Sec.312.66Assurance of IRB review.400
Sec.312.68Inspection of investigator's records and reports.400
Sec.312.69Handling of controlled substances.401
Sec.312.70Disqualification of a clinical investigator.401
Subpart E-Drugs Intended to Treat Life-threatening and Severely-debilitating Illnesses403
Sec.312.80Purpose.403
Sec.312.81Scope.403
Sec.312.82Early consultation.404
Sec.312.83Treatment protocols.405
Sec.312.84Risk-benefit analysis in review of marketingapplications for drugs to treat life-threateningand severely-debilitating illnesses.405
Sec.312.85Phase 4 studies.406
Sec.312.86Focused FDA regulatory research.406
Sec.312.87Active monitoring of conduct and evaluationof clinical trials.406
Sec.312.88Safeguards for patient safety.406
Subpart F-Miscellaneous407
Sec.312.110Import and export requirements.407
Sec.312.120Foreign clinical studies not conductedunder an IND.411
Sec.312.130Availability for public disclosure of data and information in an IND.414
Sec.312.140Address for correspondence.415
Sec.312.145Guidance documents.416
Subpart G-Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests416
Sec.312.160Drugs for investigational use in laboratory research animals or in vitro tests.416
Subpart H [Reserved]418
Subpart I-Expanded Access to Investigational Drugs for Treatment Use418
Sec.312.300General.418
Sec.312.305Requirements for all expanded access uses.419
Sec.312.310Individual patients,including for emergency use.422
Sec.312.315Intermediate-size patient populations.424
Sec.312.320Treatment IND or treatment protocol.426
21CFRPART812INVESTIGATIONAL DEVICE EXEMPTIONS428
Subpart A-General Provisions428
812.1Scope.428
812.2Applicability.429
812.3Definitions.431
812.5Labeling of investigational devices.433
812.7Prohibition of promotion and other practices.434
812.10Waivers.435
812.18Import and export requirements.435
812.19Address for IDE correspondence.435
Subpart B-Application and Administrative Action436
812.20Application.436
812.25Investigational plan.438
812.27Report of prior investigations.439
812.30FDA action on applications.439
812.35Supplemental applications.441
812.36Treatment use of an investigational device.444
812.38Confidentiality of data and information.448
Subpart C-Responsibilities of Sponsors449
812.40General responsibilities of sponsors.449
812.42FDA and IRB approval.450
812.43Selecting investigators and monitors.450
812.45Informing investigators.451
812.46Monitoring investigations.451
812.47Emergency research under 50.24 of this chapter.452
Subpart D-IRB Review and Approval452
812.60IRB composition,duties,and functions.452
812.62IRB approval.452
812.64IRBs continuing review.452
812.65[Reserved]453
812.66Significant risk device determinations.453
Subpart E-Responsibilities of Investigators453
812.100General responsibilities of investigators.453
812.110Specific responsibilities of investigators.453
812.119Disqualification of a clinical investigator.454
Subpart F [Reserved]456
Subpart G-Records and Reports456
812.140Records.456
812.145Inspections.459
812.150Reports.459
45CFRPART46PROTECTION OF HUMAN SUBJECTS463
Subpart A-Basic HHS Policy for Protection of Human Research Subjects463
46.101To what does this policy apply?(Omit)463
46.102Definitions.463
46.103Assuring compliance with this policy—research conducted or supported by any Federal Department or Agency.465
46.104—46.106 [Reserved]467
46.107IRB membership.467
46.108IRB functions and operations.468
46.109IRB review of research.469
46.110Expedited review procedures for certain kinds of research involving no more than minimal risk,and for minor changes in approved research.469
46.111Criteria for IRB approval of research.470
46.112Review by institution.471
46.113Suspension or termination of IRB approval of research.471
46.114Cooperative research.472
46.115IRB records.472
46.116General requirements for informed consent.473
46.117Documentation of informed consent.475
46.118Applications and proposals lacking definite plans for involvement of human subjects.476
46.119Research undertaken without the intention of involving human subjects.477
46.120Evaluation and disposition of applications and proposals for research to be conducted or supported by a Federal Department or Agency.477
46.121[Reserved]477
46.122Use of Federal funds.477
46.123Early termination of research support: Evaluation of applications and proposals.477
46.124Conditions.478
Subpart B-Additional Protections for Pregnant Women,Human Fetuses and Neonates Involved in Research478
46.201To what do these regulations apply? (Omit)478
46.202Definitions.478
46.203Duties of IRBs in connection with research involving pregnant women,fetuses,and neonates.479
46.204Research involving pregnant women or fetuses.479
46.205Research involving neonates.480
46.206Research involving,after delivery,the placenta,the dead fetus or fetal material.482
46.207Research not otherwise approvable which presents an opportunity to erstand,prevent,or alleviate a serious problem affecting the health or welfare ofpregnant en,fetuses,orneonates.482
Subpart C-Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects483
46.301Applicability(Omit). 483
46.302Purpose.483
46.303Definitions.483
46.304Composition of Institutional Review Boards where prisoners are involved.484
46.305Additional duties of the Institutional Review Boardswhere prisoners are involved.484
46.306Permitted research involving prisoners.485
Subpart D-Additional Protections for Children Involved as Subjects in Research486
46.401To what do these regulations apply?(Omit)486
46.402Definitions.486
46.403IRB duties.487
46.404Research not involving greater than minimal risk.487
46.405Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.487
46.406Research involving greater than minimal risk and no prospect of direct benefit to individual subjects,but likely to yield generalizable knowledge about the subjects disorder or condition.488
46.407Research not otherwise approvable which presents an opportunity to understand,prevent,or alleviate a serious problem affecting the health or welfare of children.488
46.408Requirements for permission by parents or guardians and for assent by children.489
46.409Wards.490
Subpart E-Registration of Institutional Review Boards (Omit)491
Sec.312.84Risk-benefit analysis in review of marketingapplications for drugs to treat life-threateningand severely-debilitating illnesses.405
Sec.312.85Phase 4 studies.406
Sec.312.86Focused FDA regulatory research.406
Sec.312.87Active monitoring of conduct and evaluationof clinical trials.406
Sec.312.88Safeguards for patient safety.406
Subpart F-Miscellaneous407
Sec.312.110Import and export requirements.407
Sec.312.120Foreign clinical studies not conductedunder an IND.411
Sec.312.130Availability for public disclosure of data and information in an IND.414
Sec.312.140Address for correspondence.415
Sec.312.145Guidance documents.416
Subpart G-Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests416
Sec.312.160Drugs for investigational use in laboratory research animals or in vitro tests.416
Subpart H [Reserved]418
Subpart I-Expanded Access to Investigational Drugs for Treatment Use418
Sec.312.300General.418
Sec.312.305Requirements for all expanded access uses.419
Sec.312.310Individual patients,including for emergency use.422
Sec.312.315Intermediate-size patient populations.424
Sec.312.320Treatment IND or treatment protocol.426
21CFRPART812INVESTIGATIONAL DEVICE EXEMPTIONS428
Subpart A-General Provisions428
812.1Scope.428
812.2Applicability.429
812.3Definitions.431
812.5Labeling of investigational devices.433
812.7Prohibition of promotion and other practices.434
812.10Waivers.435
812.18Import and export requirements.435
812.19Address for IDE correspondence.435
Subpart B-Application and Administrative Action436
812.20Application.436
812.25Investigational plan.438
812.27Report of prior investigations.439
812.30FDA action on applications.439
812.35Supplemental applications.441
812.36Treatment use of an investigational device.444
812.38Confidentiality of data and information.448
Subpart C-Responsibilities of Sponsors449
812.40General responsibilities of sponsors.449
812.42FDA and IRB approval.450
812.43Selecting investigators and monitors.450
812.45Informing investigators.451
812.46Monitoring investigations.451
812.47Emergency research under 50.24 of this chapter.452
Subpart D-IRB Review and Approval452
812.60IRB composition,duties,and functions.452
812.62IRB approval.452
812.64IRBs continuing review.452
812.65[Reserved]453
812.66Significant risk device determinations.453
Subpart E-Responsibilities of Investigators453
812.100General responsibilities of investigators.453
812.110Specific responsibilities of investigators.453
812.119Disqualification of a clinical investigator.454
Subpart F [Reserved]456
Subpart G-Records and Reports456
812.140Records.456
812.145Inspections.459
812.150Reports.459
45CFRPART46PROTECTION OF HUMAN SUBJECTS463
Subpart A-Basic HHS Policy for Protection of Human Research Subjects463
46.101To what does this policy apply?(Omit)463
46.102Definitions.463
46.103Assuring compliance with this policy—research conducted or supported by any Federal Department or Agency.465
46.104—46.106 [Reserved]467
46.107IRB membership.467
46.108IRB functions and operations.468
46.109IRB review of research.469
46.110Expedited review procedures for certain kinds of research involving no more than minimal risk,and for minor changes in approved research.469
46.111Criteria for IRB approval of research.470
46.112Review by institution.471
46.113Suspension or termination of IRB approval of research.471
46.114Cooperative research.472
46.115IRB records.472
46.116General requirements for informed consent.473
46.117Documentation of informed consent.475
46.118Applications and proposals lacking definite plans for involvement of human subjects.476
46.119Research undertaken without the intention of involving human subjects.477
46.120Evaluation and disposition of applications and proposals for research to be conducted or supported by a Federal Department or Agency.477
46.121[Reserved]477
46.122Use of Federal funds.477
46.123Early termination of research support: Evaluation of applications and proposals.477
46.124Conditions.478
Subpart B-Additional Protections for Pregnant Women,Human Fetuses and Neonates Involved in Research478
46.201To what do these regulations apply? (Omit)478
46.202Definitions.478
46.203Duties of IRBs in connection with research involving pregnant women,fetuses,and neonates.479
46.204Research involving pregnant women or fetuses.479
46.205Research involving neonates.480
46.206Research involving,after delivery,the placenta,the dead fetus or fetal material.482
46.207Research not otherwise approvable which presents an opportunity to erstand,prevent,or alleviate a serious problem affecting the health or welfare ofpregnant en,fetuses,orneonates.482
Subpart C-Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects483
46.301Applicability(Omit). 483
46.302Purpose.483
46.303Definitions.483
46.304Composition of Institutional Review Boards where prisoners are involved.484
46.305Additional duties of the Institutional Review Boardswhere prisoners are involved.484
46.306Permitted research involving prisoners.485
Subpart D-Additional Protections for Children Involved as Subjects in Research486
46.401To what do these regulations apply?(Omit)486
46.402Definitions.486
46.403IRB duties.487
46.404Research not involving greater than minimal risk.487
46.405Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.487
46.406Research involving greater than minimal risk and no prospect of direct benefit to individual subjects,but likely to yield generalizable knowledge about the subjects disorder or condition.488
46.407Research not otherwise approvable which presents an opportunity to understand,prevent,or alleviate a serious problem affecting the health or welfare of children.488
46.408Requirements for permission by parents or guardians and for assent by children.489
46.409Wards.490
Subpart E-Registration of Institutional Review Boards (Omit)491
