Good Clinical Practice (GCP) mandates accurate recording, handling, and storage of clinical trial information through essential documents contained in trial master files and investigator site files. The European Medicines Agency (EMA) has issued guidelines on GCP compliance and managing both paper and electronic source data, while the Medicines and Healthcare products Regulatory Agency (MHRA) offers guidance for electronic health records to meet clinical trial regulations. Effective management of trial master files is crucial for audit processes, with additional resources provided by regulatory bodies to assist sponsors and investigators.

1. Good Clinical Practice

2. • Good Clinical Practice (GCP) requires that all clinical trial information
shall be recorded, handled and stored in such a way that it can be
accurately reported, interpreted and verified.

3. • Essential documents are:
"...those which enable both the conduct of the clinical trial and the
quality of the data produced to be evaluated; and show whether the
trial is, or has been, conducted in accordance with the applicable
regulatory requirements"

4. • Many essential documents are filed in a Trial Master File / Investigator
Site File. Some, essential documents may also be source documents,
which are often generated as part of the subject’s medical care and
therefore documented and archived in medical records and other
service departments.

5. • The EMA has published Guideline on GCP compliance in relation to
trial master file (paper and/or electronic) for content, management,
archiving, audit and inspection of clinical trials (2017) which assists
sponsors and investigators to comply with the Clinical Trials
Regulations.

6. • Electronic Source Data
• Source data and other essential documents may be kept in either
paper or electronic format. The EMA published a document in
2010: Reflection paper on expectations for electronic source data and
data transcribed to electronic data collection tools in clinical trials
(PDF, 127 KB).

7. • For sites considering a move from paper medical records to electronic
health records (eHR), the MHRA have produced a position
statement on the implementation of eHR systems to ensure
compliance with the Medicines for Human Use (Clinical Trials)
Regulations 2004 (as amended).

8. • The position statement details common problems found with eHR
systems during GCP inspection and provides a comprehensive list of
factors to consider when trial sites are establishing an eHR system.

9. • A Trial Master File (TMF) should be set up at the beginning of a trial.
The essential documents that make up the file should be kept in a
secure but accessible manner. A well-kept TMF can help with
efficient trial management and can facilitate the reconstruction of the
conduct of the trial during the audit/inspection process.

10. • The GCP Inspection Working Group have produced the ‘Guideline on
the content, management and archiving of the clinical trial master file
(paper and/or electronic)’ (6 December 2018), that current assist
sponsors and investigators comply with the Clinical Trials Regulations.
In addition, the MHRA FAQs for Trial Master Files (TMF) and
Archiving provide further guidance.

11. • The TMF should be held at the coordinating site (usually the Chief
Investigator’s office or Coordinating Centre) and for multi-site trials,
copies of relevant documents should be kept at each participating site
in an Investigator Site File (ISF). Most sponsors will provide guidance
on the content and set up of the TMF/ISF based on their local
policies/procedures.