Clinical Trials Audit Preparation: A Guide for Good Clinical Practice (GCP) Inspections / Edition 1 available in Hardcover, eBook
Clinical Trials Audit Preparation: A Guide for Good Clinical Practice (GCP) Inspections / Edition 1
- ISBN-10:
- 0470248858
- ISBN-13:
- 9780470248850
- Pub. Date:
- 06/01/2010
- Publisher:
- Wiley
Clinical Trials Audit Preparation: A Guide for Good Clinical Practice (GCP) Inspections / Edition 1
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$117.95Overview
The Good Clinical Practice (GCP) audit is a tedious but necessary exercise that assures that all parties do their job properly and in compliance with the applicable FDA code. Clinical Trials Audit Preparation demystifies the audit process for all parties involved, including clinical research sponsors, clinical investigators, and institutional review boards.
This book provides a step-by-step explanation of the FDA audit procedures for clinical trials and of how pharmaceutical companies, clinical investigators, and institutional review boards should prepare for regulatory audits. The book emphasizes the processes and procedures that should be implemented before a clinical audit occurs, making this an imperative guide to any professional in the drug manufacturing industry, including drug manufacturing companies, regulatory affairs personnel, clinical investigators, and quality assurance professionals.
Among the topics discussed:
- Good Clinical Practices and therapeutic product development in clinical research
- The roles of the sponsor of a clinical investigation, the IRB, or independent ethics committee
- The roles and responsibilities of the clinical trial investigator
- The inspection preparation
- The Audit Report and the Form 483
- Warning letters issued to clinical investigators and clinical trial sponsors and their impact on product development
Product Details
ISBN-13: | 9780470248850 |
---|---|
Publisher: | Wiley |
Publication date: | 06/01/2010 |
Pages: | 272 |
Product dimensions: | 6.30(w) x 9.30(h) x 0.80(d) |
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Table of Contents
Preface xiii
Introduction xv
Background History on Clinical Research Standards xv
Glossary xvii
Chapter 1 Good Clinical Practice and Therapeutic Product Development 1
1.1 Good Clinical Practice in Clinical Research 2
1.1.1 Definition 2
1.1.2 GCP Compliance 2
1.1.3 GCP Objectives 2
1.1.4 Principles of ICH GCP 3
Clinical Trial Conduct 3
Risk Assessment 3
Subject's Rights and Safety 3
Background Information 3
Clinical Trial Protocol 3
Ethics Review and Approval 3
Medical Care of Trial Subject 4
Qualifications of Clinical Trial Personnel 4
Informed Consent Process 4
Data Management 4
Patient Confidentiality 4
Investigational Product Manufacturing, Handling, and Storage 4
Quality Assurance 4
1.1.5 GCP Applicability 5
1.2 Role of the Sponsor of a Clinical Investigation 6
1.2.1 GCP: Responsibilities of a Sponsor of a Clinical Trial 6
1.2.2 Essential Documents for the Clinical Trial 9
Retention of the Essential Documents for the Clinical Trial 9
Archiving of the Essential Documents for the Clinical Trial After Discontinuation of Development 9
Notification 10
Transfer of Data Ownership 10
Records Retention 10
1.2.3 Investigator Selection 10
Investigator's Qualifications 10
Resources at the Investigator's Site 11
Protocol and Investigator's Brochure 11
Agreement with the Investigator/Institution 11
1.2.4 Allocation of Responsibilities 11
1.2.5 Compensation to Subjects and Investigators 12
Compensation to Subjects for Trial-Related Injuries 12
Other types of Compensation to Trial Subjects 12
1.2.6 Financing 12
1.2.7 Notification/Submission to Regulatory Authorities 13
1.2.8 Confirmation of Review by IRB/IEC 13
1.2.9 Information on Investigational Products 14
1.2.10 Manufacturing, Packaging, Labelling, and Coding Investigational Products 14
Characterization, Manufacturing, and Labeling of the Investigational Product 14
Storage Conditions 14
Packaging of the Investigational Product 14
Coding and Decoding of the Investigational Product 14
Investigational Product Changes and Bioequivalence Studies 15
1.2.11 Supplying and Handling Investigational Products 15
Supply 15
Investigational Product Records 15
1.2.12 Record Access 16
Verification of Patient Consent to Record Access 16
1.2.13 Safety Information 16
Safety Issues 16
Communication of Safety Issues 16
1.2.14 Adverse Drug Reaction Reporting 17
Serious Unexpected Adverse Drug Reactions 17
SAE Reporting Compliance 17
Safety Updates and Periodic Reports 17
1.2.15 Monitoring 17
Purposes 18
Selection and Qualifications of Monitors 18
Monitoring Strategies 19
Monitor's Responsibilities 19
Monitoring Procedures 21
Monitoring Report 21
1.2.16 Audit 21
Purposes 22
Selection and Qualifications of Auditors 22
Auditing Procedures 22
Site Selection Criteria for Inspection 22
Reporting of Findings 23
Audit Certificate 23
1.2.17 Noncompliance 23
1.2.18 Premature Termination or Suspension of a Trial 24
1.2.19 Clinical Trial/Study Reports 24
1.2.20 Multicenter Trials 24
1.3 Role of the Institutional Review Board/Independent Ethics Committee (IRB/IEC) 25
1.3.1 Responsibilities 25
Document Gathering 25
Review of Documentation 26
1.3.2 Considerations for Review 26
1.3.3 Additional Information to be Provided To Subjects 26
Nontherapeutic Trials 26
Emergency Situations 26
Payment to Study Subjects 27
Payment Information in the Consent Form 27
Composition, Functions, and Operations 27
IRB/IEC Standard Operating Procedures 28
Records 29
1.4 Roles and Responsibilities of the Clinical Trial Investigator 29
1.4.1 Investigator's Qualifications and Agreements 29
1.4.2 Adequate Resources 30
1.4.3 Medical Care of Trial Subjects 30
1.4.4 Communication with IRB/IEC 31
1.4.5 Compliance with Protocol 31
1.4.6 Investigational Product(s) 32
1.4.7 Randomization Procedures and Unblinding 33
1.4.8 Informed Consent of Trial Subjects 33
1.4.9 Records and Reports 37
1.4.10 Progress Reports 38
Safety Reporting 38
1.4.11 Premature Termination or Suspension of a Trial 38
1.5 Clinical Trial Protocol and Protocol Amendments 39
1.5.1 Contents of Trial Protocol 39
1.5.2 Investigator's Brochure 42
Introduction 42
General Considerations 43
Contents of the Investigator's Brochure 43
Chapter 2 Therapeutic Products Clinical Development in the United States 47
2.1 Drug Discovery 47
2.2 Preclinical Development 47
2.2.1 In Vitro Testing 47
2.2.2 In Vivo Testing (Animal Testing) 48
2.3 Clinical Development 48
2.4 FDA Considerations for Drug Development 50
2.4.1 Pre-IND Meeting 50
2.4.2 End of Phase II Meeting 50
2.4.3 Pre-NDA Meeting 51
2.5 Phase IV, Postmarketing Surveillance and GCP 51
2.6 Quality Assurance in Clinical Research 52
2.7 FDA Inspectional Background and Data 53
2.7.1 The FDA and GCP 53
2.7.2 FDA: Responsibilities of the Sponsor (Subpart D 21 CFR 312.50 to 21 CFR 312.58) 54
2.7.3 FDA: Responsibilities of the Investigator - (Subpart D 21 CFR 312.50 to 21 CFR 312.58) 56
Investigator Recordkeeping and Record Retention 56
Investigator Reports 57
Assurance of IRB Review 57
Inspection of Investigator's Records and Reports 57
Handling of Controlled Substances 58
Disqualification of a Clinical Investigator 58
2.7.4 FDA: Responsibilities of the Institutional Review Board (21 CFR Part 56) 59
Circumstances in Which IRB Review is Required 59
Exemptions from IRB Requirement 59
Waiver of IRB Requirement 60
IRB Membership 60
IRB Functions and Operations 61
IRB Review of Research 61
Expedited Review Procedures for Certain Kinds of Research Involving No More than Minimal Risk and for Minor Changes in Approved Research 62
Criteria for IRB Approval of Research 63
Review by Institution 64
Suspension or Termination of IRB Approval of Research 64
Cooperative Research 64
IRB Records 64
Lesser Administrative Actions for Noncompliance 65
Disqualification of an IRB or an Institution 65
Public Disclosure of Information Regarding Revocation 66
Reinstatement of an IRB or an Institution 66
Actions Alternative or Additional to Disqualification 66
2.8 FDA Bioresearch Monitoring Program 67
2.8.1 Clinical Trials Inspections! Background 67
2.8.2 Program Objectives 67
2.8.3 Types of Inspections Performed by the FDA 67
Routine Inspections 67
Directed (for Cause) Inspections 68
Classification of Inspections 68
2.8.4 Who Is Inspected? 68
2.8.5 Implementation of the FDA's Application Integrity Policy 68
2.8.6 BIMO Inspections for Clinical Trials 69
2.8.7 The FDA and International GCP Inspections 74
Criteria for International Sites Selection for Inspection 76
Chapter 3 The Inspection Preparation 77
3.1 Conduct of an Internal GCP Inspection: Quality Assurance Inspection 77
3.2 Steps to Prepare for the Internal QA Inspection 78
3.2.1 Inspection of the Trial Master File (TMF) 78
3.2.2 Inspection of an Investigator Site 79
3.2.3 Inspection of the Contract Research Organization (CRO) 79
3.2.4 Inspection of Clinical Laboratories 79
3.3 The GCP Quality Assurance Unit 80
3.3.1 Scope of an Internal GCP Inspection 80
3.3.2 Outcome of an Internal Inspection 81
3.4 Steps to Prepare for the Regulatory Inspection 82
3.5 Clinical Investigator Inspections Preparation 84
3.6 What to Do When an Investigator Site FDA Inspection is Announced 84
3.7 Sponsor's Inspection Preparation 86
3.8 What to Do When Sponsors FDA Inspector Arrive Unannounced 87
3.9 The Institutional Review Board Inspections Preparation 88
3.9.1 Central IRBs 90
3.10 What to Do When an IRB FDA Inspection is Announced 91
3.11 The Investigator Site Inspection 92
3.11.1 Objective of an FDA Investigator Site Inspection 92
3.11.2 Dynamics of a Clinical Investigator's Inspection (Scope) 93
3.12 Investigator's Responsibilities 93
3.13 Types of Clinical Investigator Site Inspections 101
3.14 Inspecdonal Procedures 102
3.14.1 The Investigator Site Documentation and Organization 102
3.14.2 The Sponsor's Role in the Investigator Site Audit 103
3.14.3 The Clinical Investigator Site Inspection Step by Step: The Day of the Inspection 103
3.15 FDA Audit Procedures for Investigative Sites 104
3.15.1 Authority and Administration 104
3.15.2 Inspecting the Protocol 106
3.15.3 Inspecting Subjects' Records 106
3.15.4 Inspecting Other Study Records 109
3.15.5 Inspecting the Consent of Human Subjects 109
3.15.6 Inspecting the Institutional Review Board Documentation 110
3.15.7 Inspecting the Sponsor's Documentation and Communications at the Investigator Site 111
3.15.8 Inspecting the Investigational Product (Test Article Accountability) 112
3.15.9 Inspecting the Records Retention Process 113
3.15.10 Inspecting Electronic Records and Signatures 113
3.15.11 Inspecting Device Studies 115
3.16 FDA Inspections of International Clinical Trial Sites 115
3.17 The Audit Report and Form 483 116
3.17.1 The Exit Interview 116
3.17.2 What Is Form 483? 117
3.17.3 Responding to a Form 483 119
3.17.4 The Follow-up 121
3.17.5 Warning Letter 121
3.17.6 Regulatory Actions Against Clinical Investigators 124
Notice of Initiation of Disqualification Proceeding and Opportunity to Explain (NIDPOE) (312.70) 124
What is a Disqualification of an Investigator? 125
What is the Consent Agreement? 125
3.17.7 The Clinical Hold 125
Issue of the Clinical Hold 126
Scope of the Clinical Hold 126
Meaning of the Clinical Hold 126
Extent of the Clinical Hold 126
Lift of the Clinical Hold 127
3.17.8 Reinstatement of Disqualified Investigators 127
3.17.9 Regulatory Action Against Companies or Persons (Not Investigators): Debarment 127
Chapter 4 Analysis of Warning Letters 129
4.1 Analysis of Warning Letters Issued to Clinical Investigators 129
4.1.1 Most Common Findings of Investigator Site Inspections 129
Findings Relating to Patient Information and Consent Form and Process 129
Findings Relating to Investigator's Supervision of the Clinical Trial 133
Findings Relating to Protocol Adherence 135
Findings Relating to Records in Clinical Trials 138
Findings Relating to the Investigational Product in Clinical Trials 142
Findings Relating to the Reporting of Adverse Events 143
Findings Relating to the Institutional Review Board's Approvals and Reporting 146
Findings Relating to the Investigator Acting in a Dual Role of Sponsor-Investigator 148
4.2 An Analysis of Warning Letters Issued to Clinical Trial Sponsors 149
4.2.1 Most Common Sponsors of Clinical Investigations Findings 149
Findings Relating to the Sponsor's Responsibilities to Ensure Proper Monitoring of a Clinical Trial 149
Findings Relating to the Sponsor's Responsibilities for the Investigational Product 152
Findings Relating to the Sponsor's Records of a Clinical Investigation 152
Findings Relating to the Sponsor Obtaining an IND to Conduct a Study 153
Findings Relating to the Sponsor's Responsibilities to Secure Agreements Within Parties 153
4.3 Analysis of Warning Letters Issued to Institutional Review Boards 154
4.3.1 Most Common Institutional Review Board Findings 155
Findings Relating to IRB Operational Procedures 155
Findings Relating to IRB Initial and Continuing Review Process 159
Findings Relating to IRB Recordkeeping and Retention 160
Findings Relating to IRB Composition and Membership 162
Findings Relating to IRB Review Process 163
Findings Relating to IRB Review Process of Special Populations in Clinical Trials 165
Administrative Actions to IRBs 165
Reinstatement of a Disqualified IRB 166
Conclusions on the Findings 167
Chapter 5 Fraud and Misconduct in Clinical Research 169
5.1 What Type of Data is Falsified? 170
5.2 How is Data Falsified? 171
5.3 Why is Data Falsified? 172
5.4 Who Falsified the Data? 172
5.5 What Can be Done to Detect Fraud? 173
5.6 How Do We Prevent Fraud? 173
Appendix A Some Answers to the Most Problematic Questions in Compliance 177
How Can an Investigator Site Demonstrate That the Proper Consent Process Was Followed? 177
How Does One Demonstrate that a Subject Understood the Consent Information? 177
How Does One Demonstrate that all the Clinical Trial Procedures were Followed? 178
How Does One Demonstrate Principal Investigator Personal Involvement in the Supervision of Clinical Trial Activities? 178
Why Follow Standard Operating Procedures in Clinical Trials? 178
Appendix B Guidance for Industry-E6 Good Clinical Practice: Consolidated Guidance 179
Introduction 181
Appendix C World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects 225
A Introduction 225
B Basic Principles for all Medical Research 226
C Additional Principles for Medical Research Combined with Medical Care 228
Appendix D Nuremberg Code 231
Appendix E The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research 233
Part A Boundaries Between Practice and Research 235
Part B Basic Ethical Principles 236
Part C Applications 238
Index 245