Appendix C. ESSENTIAL RECORDS FOR THE CONDUCT OF A CLINICAL TRIAL

ICH HARMONISED GUIDELINE
GOOD CLINICAL PRACTICE (GCP) E6(R3) Step 5

23 January 2025. Date for coming into effect 23 July 2025

C.1 Introduction

C.1.1 Many records are generated before and during the conduct of a clinical trial. The nature and extent of those records generated and maintained are dependent on the trial design, its conduct, application of risk proportionate approaches and the importance and relevance of that record to the trial.

C.1.2 Determining which records are essential will be based on consideration of the guidance in this appendix.

C.1.3 The essential records permit and contribute to the evaluation of the conduct of a trial in relation to the compliance of the investigator and sponsor with Good Clinical Practice (GCP) and applicable regulatory requirements and the reliability of the results produced. The essential records are used as part of the investigator oversight and sponsor oversight (including monitoring) of the trial. These records are used by the sponsor’s independent audit function and during inspections by regulatory authority(ies) to assess the trial conduct and the reliability of the trial results. Certain essential records may also be reviewed by the institutional review board/independent ethics committee (IRB/IEC) in accordance with applicable regulatory requirements. The investigator/institution should have access to and the ability to maintain the essential records generated by the investigator/institution before and during the conduct of the trial and retain them in accordance with applicable regulatory requirements.

C.2 Management of essential records

C.2.1 Records should be identifiable and version controlled (when appropriate) and should include authors, reviewers and approvers as appropriate, along with date and signature (electronic or physical), where necessary.

C.2. For activities that are transferred or delegated to service providers by the sponsor or investigator/institution, respectively, arrangements should be made for the access and management of the essential records throughout the trial and for their retention following completion of the trial.

C.2.3 These essential records should be maintained in or referred to from repositories held by the sponsor and by the investigator/institution for their respective records. These repositories may be referred to as a trial master file (TMF). The repository held by the investigator/institution may also be referred to as the investigator site file (ISF).

C.2.4 The sponsor and investigator/institution should maintain a record of where essential records are located, including source records. The storage system(s) used during the trial and for archiving (irrespective of the type of media used) should provide for appropriate identification, version history, search and retrieval of trial records.

C.2.5 The sponsor and investigator/institution should ensure that the essential records are collected and filed in a timely manner, which can greatly assist in the successful management of a trial. Some essential records should generally be in place prior to the start of the trial and may be subsequently updated during the trial.

C.2.6 The sponsor and investigator/institution should retain the essential records in a way that ensures that they remain complete, readable and readily available and are directly accessible upon request by regulatory authorities, monitors and auditors. Alteration to the essential records should be traceable.

C.2.7 The sponsor and investigator/institution should ensure the retention of the essential records required to fulfil their responsibility. The original records should generally be retained by the responsible party who generated them.

C.2.8 In order to fulfil their responsibilities in the conduct of the trial, the sponsor and investigator/institution may need access to or copies of one another’s relevant essential records before and during the conduct of the trial. At the end of the trial, each party should retain their essential records (see sections 2.12.11 and 3.16.3(a)). The record location may vary during the trial depending on the nature of the record. For example, the investigator may access relevant essential records from the sponsor (e.g., suspected unexpected serious adverse reactions (SUSAR) reports) via a sponsor-provided portal, and these essential records would need to be retained by the investigator/institution at the end of the trial.

C.2.9 When a copy is used to permanently replace the original essential record, the copy should fulfil the requirements for certified copies.

C.2.10 Some records are typically maintained and retained only by the sponsor (e.g., those related solely to sponsor activities such as data analysis) or only by the investigator/institution (e.g., those that contain confidential participant information). Some records may be retained by the sponsor and/or the investigator/institution.

C.2.11 Careful consideration should be given to the sharing of records when there are blinding considerations and when the records are subject to applicable data protection legislation. For the sharing of essential records with service providers, see section C.2.2.

C.2.12 Certain essential records may not be specific to a trial but may be related to the investigational product, facilities or processes and systems, including computerised systems, involved in running multiple trials and retained outside the trial-specific repositories (e.g., Investigator’s Brochure, master services agreements, standard operating procedures, validation records).

C.3 Essentiality of trial records

C.3.1  The assessment of whether a record is essential and has to be retained should take into account the criteria below. Such assessment, whilst important, is not required to be documented. A structured content list for storage repository(ies) may be used to prospectively identify essential records. An essential record:

(a) Is a document that is submitted to or issued by the regulatory authority or IRB/IEC, including related correspondence and those documenting regulatory decisions or approvals/favourable opinions;

(b) Is a trial-specific procedure or plan;
 
(c) Is relevant correspondence or documentation of meetings related to important discussions and/or trial-related decisions that have been made related to the conduct of the trial and the processes being used;

(d) Documents the conduct of relevant trial procedures (e.g., database lock checklist produced from following data management standard operating procedures (SOPs));

(e) Documents the arrangements between parties and insurance/indemnity arrangements;

(f) Documents the compliance with the requirements and any conditions of approval from the regulatory authority or the favourable opinion of the IRB/IEC;

(g) Documents the composition and, where appropriate, the functions, correspondence and decisions of any committees involved in the trial approval or its conduct.

(h) Demonstrates that a trial-specific computerised system is validated and that non-trial-specific systems (e.g., clinical practice computerised systems) have been assessed as fit for purpose for their intended use in the trial;

(i) Is a document that has been authorised/signed by the sponsor and/or investigator to confirm review or approval;

(j) Is, where necessary, documentation that demonstrates signatures/initials of staff undertaking significant trial-related activities; for example, completing data acquisition tools;

(k) Documents what information was provided to potential trial participants and that participants’ informed consent was appropriately obtained and maintained;

(l) Documents that sponsor personnel involved in the trial conduct and individuals performing significant trial-related activities on their behalf are qualified by education, training and experience to undertake their activities;

(m) Documents that the investigator and those individuals delegated significant trial-related  activities by the investigator are qualified by education, training and experience to undertake their activities, particularly where the activities are not part of their normal role;

(n) Contains the data as well as relevant metadata that would be needed to allow the appropriate evaluation of the conduct of the trial;

(o) Is a document related to the sponsor or investigator oversight of trial participant safety during the trial, including compliance with safety reporting requirements between sponsors and investigators, regulatory authorities and IRBs/IECs and informing trial participants of safety information as necessary;

(p) Documents that service providers are suitably qualified for conducting their delegated or transferred activities;

(q) Documents that laboratory activities and other tests used in the trial are fit for purpose;

(r) Documents sponsor oversight of investigator site selection and monitoring and audit of the trial, where appropriate, and provides information on arising issues/noncompliance and deviations detected and implementation of corrective and preventative actions;

(s) Documents the compliance with the protocol and/or procedures for management and statistical analysis of the data and production of any interim report and the final report;

(t) Documents the collection, chain of custody, processing, analysis and retention or destruction of biological samples;

(u) Provides relevant information on the investigational product and its labelling;

(v) Provides information about the shipment, storage, packaging, dispensing, randomisation and blinding of the investigational product;

(w) Provides, where appropriate, traceability and accountability information about the investigational product from release from the manufacturer to dispensation, administration to trial participants, return and destruction or alternative disposition;

(x) Provides information on the identity and quality of the investigational product used in the trial;

(y) Documents processes and activities relating to unblinding;

(z) Documents the recruitment, pre-trial screening and consenting process of trial participants and their identity and chronological enrolment as appropriate;

(aa) Documents the existence of the trial participants and substantiates the integrity of trial data collected. Includes source records related to the trial and medical treatments and history of the trial participants;

(bb) Defines processes/practices in place in the event of a security breach in order to
protect participants’ rights, safety and well-being and the integrity of the data.

C.3.2 Applying the criteria in section C.3.1, the trial records that are considered essential are listed in the Essential Records Table, and these should be retained when produced. This table is not an exhaustive list, and other trial records may also be considered essential by the sponsor or the investigator.

С.3.3 For some trial records listed in the Essential Record Table, their presence and nature are dependent on the trial design, trial conduct and risk proportionate management of the trial and may not be produced.

Author: © European Medicines Agency, 2025. Reproduction is authorised provided the source is acknowledged.

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