Trial Master File: E-Mail Communications in Clinical Studies
Communications associated with key decision making and trial conduct is commonly an area raised as deficient during GCP audits or inspections. The communication section in the (e)TMF frequently lacks the relevant e-mail threads.
In order to improve the process of filing e-mail communications in the (e)TMF and provide recommendations to the life sciences industry on the management of e-mail communications generated throughout the conduct of a clinical study, the Trial Master File (TMF) Reference Model published on 31st July 2020 a Guidance for the Management of e-Mail Communication in Clinical Studies.
The guidance reinforces that those e-mail communications that enable evaluation of the conduct of the study; key decisions made during the study; the integrity of the study data; and compliance of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements are considered “Essential Documents” (Ref. ICH GCP E 6(R2) 1.23) and should be retained in the (e)TMF.
The guidance provides clear filing-email practices, including but not limited to the best approach to the filing of e-mails, filing responsibility, how to handle email treads and attachments, periodic review of e-mails, GDPR implication, and e-mail archiving and preservation. It also lists the main references within regulations and guidelines covering this topic.
Some takeaways after reviewing the guidance that are worth to highlight are the following:
Implement a “file-as-you-go” strategy to ensure that the TMF is always continuously up-to-date and inspection ready. Where this is not in place or not possible, organizations should nonetheless define in the TMF Plan the location of relevant communications in the (e)TMF and periodically perform completeness and quality checks to ensure that relevant communications filed are in scope.
Each organization should determine the filing format(s) acceptable for the retention of e-mails in the eTMF. If working with third parties, e-mail format (as well as handling, storage, management, and transfer process) should be agreed in advance and documented in the TMF Plan.
For legal purposes, it is recommended (where possible) to retain e-mails in their native format (e.g. MSG for Outlook e-mails, EML for Google-mail, Thunderbird etc.) along with all associated metadata to preserve provenance, authenticity, integrity, and evidential value. |
For regulatory inspection purposes, it is acceptable to retain e-mails in non-native format (e.g. in paper format or PDF format) although caution should be exercised to maintain the integrity of the e-mail as much as possible. |
Filing Responsibility. Relevant communications should be filed in the (e)TMF by either the originator of the communication (the default procedure), or the primary recipient of the communication if the originator does not have access to the (e)TMF.
If an e-mail contains an attachment that is already filed within the eTMF, the e-mail referencing the attachment does not need to be filed again as part of the e-mail. However, if the content of the e-mail message is relevant, file the e-mail including the attachment as a relevant communication. Attachments embedded within the body of an e-mail risk being lost during rendering (e.g. to PDF for archiving purposes) and so should be added as an attachment separately. The attachments should comply the requirements agreed in the TMF Plan or the organization’s specific SOP e.g. not password protected and in an acceptable file format.
It is recommended to avoid the use of embedded links in e-mails because of the difficulties of maintaining traceability between the e-mail and contents in the embedded link.
Periodic review of e-mails. Organizations should establish formal procedures to periodically examine the (e)TMF for the presence of relevant communications.
Organizations should develop guidelines and measures to safeguard personally identifiable information that may be contained within e-mails retained in the (e)TMF.
Archiving. If electronic communications are retained in a separate repository, regulations do not stipulate the format in which relevant communications should be archived, only that organizations should take care to ensure that the archive maintains all documents (including relevant e-communications) so that for the duration of the required retention period they remain complete and legible period of retention; can be made available upon request; and are non-modifiable.
REFERENCES
Trial Master File (TMF) Reference Model. Guidance for the Management of e-Mail Communications in Clinical Studies. July 2020.
EMA/INS/GCP/856758/2018 Good Clinical Practice Inspectors Working Group Guideline on the content, management and archiving of the clinical trial master file (paper and/or electronic). December 2018
International Council for Harmonization (ICH): ICH Harmonized Guideline, Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). Step 4, version 9 November 2016.
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Author: Dr Leire Zúñiga, Director and Principal GCP Consultant
PHARMITY, 26th of October 2020
