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 through 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.  Alternately, 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 eTMF.

The Code of Federal Regulations states in 21 CFR 312.50:
“Sponsors are responsible for… ensuring that the investigation(s) is conducted in accordance with 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 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, European Union, and Japan to facilitate mutual acceptance of clinical data by the regulatory authorities in these global jurisdictions.

The ICH document provided guidance for 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 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.

Areas Covered

Course Level- Intermediate

Who Should Attend    

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 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.

Topic Background  

  The recent draft guidance from 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 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 industry. As with all guidance documents from FDA, it provides the Agency’s most current thinking on a subject.