Direct Access to eTMF for Inspectors

October 31, 2013

  • eTMF Best Practices

The time has finally come where TMF inspections are conducted by health authorities who directly inspect a sponsor’s eTMF rather than requesting (or accepting) paper.  The 2013 TMF Reference Model survey reported the following trends in Health Authority inspections:

inspector direct access for eTMF


The MHRA GCP Guide defines the agency’s expectations about the ability to directly inspect an eTMF:

“The inspectors will require direct access to the TMF, which means reviewing the TMF as used by those conducting the trial. Inspectors have in the past been provided with an ‘artificial TMF’ or ‘snapshot’ which consisted of a copy of the official TMF being used and led to issues with documentation not being consistent with that of the official TMF.”


MHRA also clarified how they plan to access the system: “MHRA GCP inspectors will require direct access to the eTMF system (not a copy), without reliance on an eTMF ‘super-user’, so the system should ideally facilitate a read-only ‘inspector or auditor view.”


The EMA “Reflection paper on GCP compliance in relation to trial master files (paper and/or electronic) for management, audit and inspection of clinical trials” reinforces these same concepts, and also emphasizes the need for the system to be user-friendly, stating “Any training should be an option for the inspector to choose and is anticipated to be very brief (taking no more than an hour).”


One of the more interesting presentations at the recent DIA Electronic Document Management meeting in San Diego concerned allowing a Health Authority’s inspectors direct access to electronic Trial Master Files to conduct their inspections.  Lisa Mulcahy of Mulcahy Consulting, LLC, shared her experiences in working with companies who are planning to support direct access to eTMFs, or who have done so already.


Lisa feels that the industry often holds itself back from making progress in providing inspection ready eTMFs.  She hears such excuses as:


  • “Where is it stated in the regulations or laws?”
  • The TMF content is not inspection-ready or complete
  • “We haven’t had to do it to yet, so we’ll wait until we have to”


Instead, sponsors should be proactively planning to provide direct access.  One significant consideration is that the documents comprising a TMF almost always extend well beyond the eTMF itself to documents in other systems.  Examples include CTMS, EDC, legal systems, safety systems, training systems, quality management systems, and many more.  Content could potentially reside in file systems, vendor archives, file cabinets, and etc.   A comprehensive plan is needed to identify what TMF elements exist where, and how access would be provided to an auditor that required it.


Inspection readiness of all sources and archives cannot be overstressed.  Lisa recommends a concretely defined updated process for preparation and conduct of inspections when DIRECT access is to be provided – and no more war rooms!


The presentation also touched upon the very real need for systems that an inspector can learn to use quickly.  Although the EMA states that an hour may be used for training, the audience reported that an inspector’s tolerance is more likely limited to about fifteen minutes of training.  Although the EMA refers to this training as optional, most audience members felt that they were justified in requiring training by ensuring that their SOPs do not allow untrained persons to use a system.


Wingspan’s experience (as reported by our clients) is that direct access by the health authorities has been very successful in facilitating audits when a well-designed eTMF is combined with a well-designed process.  Inspections have been completed in a timely manner with a reduced volume of queries and requests from the regulators.


Note: Those of you who are DIA members and attended the conference should be able to access the presentation at some point on the DIA Website. [Title: Considerations for Providing DIRECT Access to the eTMF (and other content repositories) for Health Authority Inspections]