Good Clinical Practice: A Question & Answer Reference Guide - May 2012 - (Page 403)

By Joanne Malia Associate Director, Medical Research Process Management, Purdue Pharma, L.P. and Earl Hulihan Senior Vice President, Regulatory Compliance, Medidata Solutions Worldwide LLC This section has been updated from a chapter originally developed by Lisa A. Olson, John C. McKenney, and Keith Benze of SEC Associates, Inc., and subsequently updated by Sandra SAM Sather of Clinical Pathways, LLC The use of technology and computerized systems in the conduct of clinical trials, which began well over two decades ago as “cutting edge technology,” has now become more common with the various stakeholders (sponsors/ CROs, investigators, IRBs) that participate in clinical trials. As early as 2007, in the “Guidance for Industry, Computerized Systems Used in Clinical Investigations,” FDA acknowledged that they would accept original data “recorded by direct entry into a computerized system” as well as accept certified copies of original data, defined as a “copy of original information that has been verified, as indicated by a dated signature, as an exact copy having all of the same attributes and information as the original.” “With the increasing use of computerized systems in clinical studies, it is common to find at least some source data documented electronically,” the FDA acknowledged in its December 2010 draft guidance entitled, “Electronic Source Documentation in Clinical Investigations.” Today, industry analysts estimate that approximately 50 percent of all clinical trials include research sponsors’ use of electronic data capture (EDC) or related electronic tools to improve efficiency and productivity, and that this will approach 80% by 2012 (Oracle, 2009). Further, in the last several years, clinical research sites’ use of technology for supporting source data (i.e., electronic health records and other electronic source technology) have also increased due in large part to the desire for efficiencies, public discussion on medical errors and the associated federal push for the implementation of a national electronic health record by 2014. Technological advances such as widespread broadband Internet, web accelerators, hosted collegial design systems, open APIs that allow system integrations, centralized (compact) servers, virtual machines, and highcapacity servers have transformed the way that industry approaches clinical trial strategies. Clinical trials have also increased in size and complexity, and electronic solutions are permitting companies to expand study designs and accelerate data collection, management, transmission, storage and retrieval. The electronic age has introduced new regulatory considerations and requirements within and outside of clinical research standards (e.g., FDA Part 11 and HIPPA Security Rule). In particular, the utilization of electronic signatures at the investigational site as part of eCRFs and Case Books, and case histories in electronic health records is accompanied by increased regulatory responsibilities for sponsors, technology providers, and investigators. On March 20, 1997, the FDA issued a final regulation entitled 21 CFR 11: ELECTRONIC RECORDS; ELECTRONIC SIGNATURES, commonly referred to as “Part 11,” which has been a critical factor in the transition from paper-based to electronic records. The purpose of the regulation was to provide criteria under which the FDA would consider electronic records to be equivalent to paper records, and electronic signatures to be equivalent to traditional handwritten signatures. As a result, Part 11 also provided a framework for electronic data capture (EDC) and record keeping in clinical trials. To fully understand the implications that Part 11 has had on the clinical trial landscape, one must review the developments over the years since it was issued. Immediately following Part 11’s implementation, sponsors adopted a conservative approach to Part 11 compliance, by considering all electronic systems and/or devices directly or indirectly related to the clinical trial process as subject to Part 11’s provisions. In the subsequent five years, the FDA attempted to provide insight and direction on complying with Part 11 in areas such as validation, time stamps, audit trails, and maintenance of electronic records by drafting six guidance documents and one compliance policy Section 11: Computerized Systems, e-Clinical Trials, and Electronic Records Rules 403

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2012

Good Clinical Practice: A Question & Answer Reference Guide - May 2012
Table of Contents
Introduction
Section 1: GCP Regulations, Standards and Guidelines for Clinical Research
Section 2: Investigators/Sites
Section 3: Form FDA-1572/Statement of the Investigator
Section 4: Study Sponsors and Clinical Trial Monitoring
Section 5: Informed Consent
Section 6: Source Data/Documentation
Section 7: Clinical Trial Protocols/Protocol Changes/Protocol Violations
Section 8: Institutional Review Boards
Section 9: Drug/Study Safety and Safety Reporting
Section 10: FDA Inspections, Quality Assurance Activities, and Study Auditing
Section 11: Computerized Systems, e-Clinical Trials, and Electronic Records Rules
Section 12: Patient Recruitment
Section 13: Conflicts of Interest/Financial Disclosure
Section 14: The HIPAA Privacy Rule and FDA-Regulated Clinical Trials
Section 15: Drug Accountability, Administration, and Labeling
Section 16: Fraud, Negligence, and Regulatory Non-Compliance
Section 17: Subject Diaries
Section 18: GCP and Clinical Research Standards in the European Union and An Interview with Fergus Sweeney, Ph.D., EMA Head of Sector, Compliance and Inspection
Section 19: Clinical Trial and GCP Standards in Selected Leading Countries/Regions: Latin America, China, Russia, Ukraine, and India
Section 20: GCP Compliance Statistics and Trends
21 CFR Part 11 — Electronic Records; Electronic Signatures
21 CFR Part 50 — Protection of Human Subjects
21 CFR Part 54 — Financial Disclosure by Clinical Investigators
21 CFR Part 56 — Institutional Review Boards
21 CFR Part 312 — Investigational New Drug Application
ICH Consolidated Guideline on Good Clinical Practice (E6)
ICH Guideline on Clinical Safety Data Management (E2A)
European Union Clinical Trials Directive
European Union Good Clinical Practice Directive

Good Clinical Practice: A Question & Answer Reference Guide - May 2012