TMF Paper Originals – Should they Stay or Should They Go?

October 29, 2012

  • eTMF Resources

Sponsors and CROs adopt electronic Trial Master File (eTMF) systems for a variety of reasons, but the end goal is to reduce the cost, time, and risk associated with maintaining a compliant TMF. The more processes can become 100% electronic, the greater the benefit. However, many documents still originate in paper form (often with handwritten signatures) and are scanned into the eTMF. In an ideal world, the paper would be discarded at that point so that it would not have to be transferred to an archive location and maintained for a retention period.

However, it’s not that easy. Normally, the paper document remains the official record unless specific steps are created to create a Certified Copy, which is defined by the FDA as

“…a copy of original information that has been verified, as indicated by a dated signature, as an exact copy having all of the same attributes and information as the original.” (See Guidance for Industry Computerized Systems Used in Clinical Investigations.)

The FDA does not define this process in detail. To address this gap, the Special Interest Area Community for Document and Records Management within the DIA recently supported an initiative to create a framework for the process and parameters concerning the destruction of paper documentation. The resulting Framework for the Destruction of Paper is a meticulously researched, detailed document that establishes recommendations for the legal and regulatory basis for the destruction of paper records. The Framework recommends the destruction of that paper following a verified conversion of the document into a digital format, conditional on the following:

  1. A qualified organizational process is in place and monitored that ensures the digitized copy 
is a complete and accurate representation of the paper version;
  2. The digitized copy is placed in a validated ECMS; and
  3. A training plan covering the process flow and applicable SOPs has been created, is available within the organization, and users have successfully completed the training.

However, agencies haven’t officially ruled on the acceptability of destroying paper originals, only implied that certified copies are satisfactory replacements.

This leaves sponsors, CROs and investigators in the uncomfortable position where they aren’t sure if paper originals must be retained. As usual in the risk-averse life sciences environment, almost everyone continues to ship originals off to Iron Mountain. This is especially frustrating as authorities have increasingly signaled their willingness to – and even preference for – conducting TMF audits in an eTMF environment. (For comments on eTMF from a MHRA inspector, see GCP Inspection of Trial Master Files.)

So what’s next? Most stakeholders will wait for a position from the authorities – a goal that is being pursued by the working group that produced the Framework.

Update: The UK Medicines and Healthcare Products Regulatory Agency (MHRA) touched upon this topic in the TMF chapter of their recently issued Good Clinical Practice Guide.  Some important points:

  1. The use of an eTMF would be considered as a prerequisite to the sponsor’s being able to destroy paper records and reduce storage requirements.
  2. Transfer  of the document to an eTMF repository could enable earlier destruction of the paper original.
  3. It’s still possible at this point that inspectors could request original paper records.

A duplicate paper TMF need not be retained; the reasons for this include the following:

  1. Document may only have existed and been used in an electronic format (for example, a spreadsheet used for OC of edit check programs).
  2. A paper document may be a copy of an original located elsewhere (for example, investigator’s signed CV).
  3. Documents do not have wet-ink signatures, thus the electronic version is an exact copy of the paper version that has been in the TMF (provided there are no additional annotations made, handwritten or otherwise – for example, receipt  stamps, fax machine header).

MHRA was kind enough to clarify this point for me in an email.  They explained that there is no need to retain exact duplicates – however sponsors and other responsible individuals should bear in mind the requirements of an eTMF that are outlined in the GCP Guide and the organisation would have to have every confidence that the eTMF was accurate and complete before any paper copies were destroyed.  They also stressed that ‘wet ink’ is not limited to signatures, but also encompasses any original writing such as notations.