The TMF: Climbing New Heights!

The Trial Master File, the TMF, is becoming more important in clincal trials. This page will cover different resources including information about the TMF Reference Model, a project of the DIA. I also want to discuss developments in Europe that may impact clinical trials in the United States. What documents do we need and in what format? The 29th of October, 2010 is day one of the TMF page. I will be adding more in the days, weeks, and months to come.

My own personal experience with the TMF began when I started conducting CRO audits and Mock FDA Sponsor audits. More and more I found that when TMFs were transferred between a CRO and a sponsor no one looked. I started looking and was amazed at what I found. Remember the TMF contains the documentation of your application. There’s an old FDA saying, “If it wasn’t documented, then it’s just a rumor.” Actually the same thing has been said many ways, and not just by FDA. However, the point is clear. Your TMF is your documentation of what happened during the clinical trial. Here are some links that I hope you find of interest. But first a few important updates.

Update: 10 February 2011: Some Important News! Version 1.1 of the TMF Reference Model has been finalized. Full credit is due to the hardworking Co-Chairs Karen Redding and Lisa Mulcahy along with their team of zone leads, Kathleen, Lisa, Maryanne, Jennifer, Sam and Eldin. This has taken a lot of hard work and it was done by volunteers.

TMF Reference Model_Version 1.1_Final_09Feb11

The TMF Reference Model is a project of a DIA workgroup. Learn more about this effort:

GxP Perspectives Guest Commentary on TMF Reference Model

The TMF blog address

“EDM Corner”


Update posted 28 JAN 2011– This article discusses criticism of MHRA in a government report that could impact how regulatory agencies inspect the TMF. Academy of Medical Research Report by Nick Taylor in Outsourcing-Pharma

European Medicines Agency:

Detailed Guidance on TMF

EMA Reflection Paper on Electronic Source Data

Here is a hard to find document from the UK with Amendment 31A Which th MHRA uses in TNF Inspections:

The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006


Guidance for Industry: Computerized Systems Used in Clinical Investigations

UPDATE 6 January 2011: Two Important New GCP Documents:

There is a Draft Guidance on Electronic Source Documentation in Clinical Investigations. The comment period is for 90 day (April 4, 2011 ?)

There is a new Final Rule on required elements of Informed Consent. You can read the Federal Register Announcement here that includes FDA comments in the preamble. The exact change in 21 CFR Part 50 is:

“Sec. 50.25 Elements of informed consent.

* * * * *
(c) When seeking informed consent for applicable clinical trials,
as defined in 42 U.S.C. 282(j)(1)(A), the following statement shall be
provided to each clinical trial subject in informed consent documents
and processes. This will notify the clinical trial subject that
clinical trial information has been or will be submitted for inclusion
in the clinical trial registry databank under paragraph (j) of section
402 of the Public Health Service Act. The statement is: “A description
of this clinical trial will be available on
http:[sol][sol], as required by U.S. Law. This
Web site will not include information that can identify you. At most,
the Web site will include a summary of the results. You can search this
Web site at any time.”

Replies to Email Inquiries to FDA- Review the section:

Recordkeeping and Record Retention.”

Please Read Other GxP Perspectives posts on the trial master file:

Reflecting on the TMF

TMF Compliance Documents from FDA


Additional ARTICLES on the TMF

TMF GxP Perspectives

There are Numerous Articles on the TMF

Read about Electronic TMFs at:

Applied Clinical Trials eTMF Article

And CDISC: Applied Clinical Trials: CDISC Clinical Research Glossary

Read about TMF solutions:

ClinPage Article on the TMF

TMF Checklist

Yes, there are SOPs on the TMF:

Creation and Maintenance of the TMF



TMF Defined!

And just what does “TMF” stand for, anyway”

TMF Definitions

Please submit your suggestions for the TMF Page

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