Validating Systems used for Clinical Investigations in Compliance with FDA’s Updated Draft Guidance for 21 CFR Part 11, Electronic Records/Signatures

Update to FDA’s Draft Guidance on 21 CFR Part 11, Electronic Records/Signatures Used for Clinical Investigations

Paperless Clinical Investigation Processes and Documentation: Leveraging Electronic Record and Signature Capability to Streamline these

Companies engaged in the conduct of human clinical trials must adhere to specific government regulatory requirements. Certain documents, content, and images related to a clinical trial must be stored and maintained, and depending on the regulatory jurisdiction, this body of information may be stored in a trial master file (TMF).  All of the data and documents supporting the planning, conduct, and evaluation of a clinical trial must be of the highest integrity, which must be maintained throughout their entire life cycle.  Computer System Validation will be discussed as a key methodology for meeting all of these requirements and assuring data/document integrity.

The TMF includes all of the documentation that a sponsor must record to demonstrate that they have met their obligations for the conduct of a clinical trial.  Alternatively, an electronic Trial Master File, or eTMF, can be used to collect/create and manage all of the necessary data and documentation.  We will discuss the benefits and challenges of moving to an eTMF or maintaining a hybrid solution that includes both a paper TMF and an eTMF.

The Code of Federal Regulations states in 21 CFR 312.50:

“Sponsors are responsible for… ensuring that the investigation(s) is conducted by the general investigational plan and protocols contained in the IND.”

The European Directive 2005/28/EC states:

“…trial master file shall consist of essential documents, which enable both the conduct of a clinical trial and the quality of the data produced to be evaluated.”

ICH GCP, Section 8.1 describes “essential documents” as those that individually and collectively permit the evaluation of the conduct of a trial and the quality of the data produced.

A consolidated guidance for the industry on Good Clinical Practice (GCP) in 1996 was published by the International Conference on Harmonization (ICH). The objective was to provide a unified standard for the United States, the European Union, and Japan to facilitate mutual acceptance of clinical data by the regulatory authorities in these global jurisdictions.

The ICH document guided companies in all ICH regions to establish trial master files that contain key documents that enable the evaluation of the conduct of a trial and the quality of data produced uniformly by all jurisdictions involved. In the US, there is no specific requirement from the FDA for companies to prepare a trial master file, but if the regulatory authority requires ICH GCP to be followed, then there is consequently a requirement to create and maintain a trial master file.

Documents contained in the TMF must be available for inspection by the appropriate regulatory authorities at any time during and after the conduct of a clinical trial and must be submitted to support the request for product approval. This is true for pharmaceuticals, biologics, and medical devices.  More recently, tobacco and tobacco-related products have come under regulation by FDA, and will also be discussed.

Learning Objectives:-

• Learn how to identify “GxP” Systems
• Learn about the FDA’s current thinking about technology and software development, and how this will impact the industry
• Understand the complexities and challenges of validating systems used in clinical trial work, and how to strive for greater interoperability of the many systems involved and streamline the workflows
• Understand the importance of developing a data governance approach to managing the vast amounts of data and documents generated as part of a clinical trial
• Learn about electronic Trial Master Files (TMFs) and how these should be prepared, including the essential documents for three phases of a trial: before starting, during execution, and after completion of work
• Learn about the System Development Life Cycle (SDLC) approach to validation, and how the traditional Computer System Validation (CSV) and newer Computer Software Assurance (CSA) approaches compare
• Learn the pros and cons of an Agile vs. Waterfall approach
• Learn about cloud computing and Software as a Service (SaaS) systems that can be embraced and validated effectively
• Understand how to maintain a system in a validated state through the system’s entire life cycle
• Learn about the policies and procedures needed to support your validation process and ongoing maintenance of your systems in a validated state
• Finally, understand the industry best practices that will enable you to optimize your approach to validation and compliance for key systems used in clinical investigations based on risk assessment to ensure data integrity is maintained throughout the entire data life cycle

Areas Covered:-

• GxP Data and Computer Systems Regulated by FDA
• Computer System Validation (CSV)
• The System Development Life Cycle (SDLC) Methodology
• Risk Assessment
• GAMP®5 Software Categorization
• Validation Strategy and Planning
• Functional Requirements Specification (FRS)
• Design/Configuration Specifications
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
• System Acceptance and Notification of Release into Production
• Maintenance and Operational Support of FDA-Regulated Computer Systems
• Policies and Procedures to Support CSV
• Training and Organizational Change Management (OCM) Supporting CSV Activities
• Trial Master File (TMF) background and rationale
• The essential documents to include in a TMF
• Organizing and maintaining a TMF
• Standard Operating Procedure required to support TMF
• Inspection of TMF records
• Electronic TMF (eTMF)
• Q&A

Background:-

The recent draft guidance from the FDA on electronic records and signatures (March 2023) provides information for sponsors, clinical investigators, institutional review boards, contract research organizations, and other interested parties on the use of electronic systems, electronic records, and electronic signatures in clinical investigations of foods, medical products, tobacco products, and new animal drugs under FDA regulations. The FDA draft guidance revises the draft guidance for industry issued in June 2017 entitled Use of Electronic Records and Electronic Signatures in Clinical Investigations Under 21 CFR Part 11 — Questions and Answers and, when finalized, will supersede the guidance for industry entitled Computerized Systems Used in Clinical Investigations (May 2007).

The recent draft guidance provides recommendations regarding the requirements, including the requirements under 21 CFR part 11, under which the FDA considers electronic systems, electronic records, and electronic signatures to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper. While it provides insight and clarification, it does not include any new requirements for the industry. As with all guidance documents from the FDA, it provides the Agency’s most current thinking on a subject.

Why Should You Attend:-

Anyone involved in a clinical investigation with responsibility for data, documents, and other artifacts that must be created and maintained with integrity must understand how systems interact, how data flows, and how these critical assets are managed through their entire life cycle. In particular, they are regulated by the FDA and must meet all Agency requirements, including those for validation, 21 CFR Part 11, the FDA’s guidance for electronic records and electronic signatures, data integrity, and Good Clinical Practice (GCP).

Whether you are working for a Clinical Sponsor, CRA, laboratory testing clinical trial samples, or in any way involved in the mechanics of setting up a clinical TMF or eTMF, you will benefit by learning about how to meet compliance, improve the quality of data, documents, and artifacts, and reduce overall costs.

Who will Benefit:-

• Information Technology Analysts
• Information Technology Developers and Testers
• Software Quality Assurance Professionals
• QC/QA Managers and Analysts
• Analytical Chemists
• Compliance and Audit Managers
• Laboratory Managers
• Automation Analysts
• Manufacturing Specialists and Managers
• Supply Chain Specialists and Managers
• Regulatory Affairs Specialists
• Regulatory Submissions Specialists
• Risk Management Professionals
• Clinical Data Analysts
• Clinical Data Managers
• Clinical Trial Sponsors
• Computer System Validation Specialists
• GMP Training Specialists
• Business Stakeholders/Subject Matter Experts
• Business System/Application Testers
• Vendors responsible for software development, testing, and maintenance
• Vendors and consultants working in the life sciences industry who are involved in computer system implementation, validation, and compliance