From hundreds to thousands of pages, the trial master file (TMF) contains every last bit of data associated with a trial including, under Good Clinical Practice (GCP), the signatures of all the investigators. Many key pieces of the electronic common technical document (eCTD) are drawn from the TMF.

Surprisingly, there is little software available for nudging the TMF into the Dickensian present of the pharmaceutical industry. The people at Pharmavigilant have a solution. So does the alliance of Datapharm Australia and Docbanq.

But as the world moves toward larger and larger volumes of data, an electronic TMF makes intuitive sense. The people at Phlexglobal, based in Amersham, England, have been helping clients manage TMFs in both paper and digital incarnations for five years. The firm has recently bundled software with its TMF services.

TMF Evangelist

Phlexglobal’s Karen Roy presides over eTMF solutions. She notes the company traditionally operated as a contract research organization. It got its start supplying both clinical research associates (CRA) and clinical trial administrators (CTA). The latter role was not so well known, Roy says, but the company has tried to establish it as a career in its own right.

Phlexglobal offers a variety of its services related to the TMF. The firm is quite familiar with the dissemination of key components of the TMF across time zones and company fire walls. Some large sponsors, she says, will not have easy access to a TMF during a trial, especially if it lives at a CRO.

Roy says that Phlexglobal encounters islands of paper that must be carefully reassembled into the whole package. But as the industry globalizes, those islands are getting farther apart.


“Generally, everyone has their own paper,” she says. “Some might sit in Germany, in the U.S., in Spain. You can have totally decentralized paperwork. If you use a regulatory CRO, they’ll have their own paper. You end up with paper everywhere.”

She adds that one nerve-wracking aspect of compiling the TMF on paper, especially in a decentralized industry, is the uncertainty of knowing whether it’s complete. “One of the things you don’t know is: have you got everything?” Roy says. There’s also the matter of eliminating unnecessary duplicates that have been maintained in multiple locations. “You end up with a huge duplication and a huge number of trees that get killed. You end up with paper copies everywhere. We’re trying to reduce that.”

In some projects, several teams will be needed to manually assemble a complete TMF at the end of the study. “We will send teams in to pull it together,” Roy says. But software can also help, and ensure that an emergency (such as a flooded or burned warehouse with the hard copy of a TMF) doesn’t become a catastrophe. “If you only have it on paper, once it’s gone, it’s gone,” says Roy.

Searching Everything

The company’s software and service package, launched in mid-2007,  is called PhlexEview. It allows any relevant materials, including email, to be incorporated into the final TMF. There are several options for how and where the components to the TMF are scanned into Phlexglobal’s system. Using PhlexEview, the firm (or in some cases the customer) scans in the paper documents. These are rendered as text with optical character recognition (OCR) and indexed.

Naturally, the metadata around each component document within a TMF must be manually entered and reviewed. But once that’s done, it’s easy to search and locate what’s inside the TMF. You can find all reports of monitors or any other relevant type of data. You can search by document date or synchronization.

In short, an electronic, software-based TMF is what the public probably assumes drug companies already have. But Roy says many companies in the industry have barely gotten their heads around the problem, much less around a solution.

Even when software is involved, TMF generation is not a mechanical, robotic process. Expertise is required to put each document in the right place. “You need experts to be able to look at the structure and work out where the documents go,” she says. “There’s so much paper involved in the TMF, it’s never just a technical system. There is more to it.” Software doesn’t change that.

Process, Changed

Aside from the control of the documents, Roy says PhlexEview offers a different way of working on a TMF. There are fewer all-nighters at the end of the process. The sheer existence of the system encourages far more proactive work. Visibility into the documentation creates a less burst-driven workflow. It’s a more gradual way of compiling the TMF. “You can check up on when people have put something in,” says Roy. “You don’t have it all going in at the end.” 

The software allows more granular access. A CRO or another development partner can be given access to one portion of the TMF, but not the entire thing.

Slow Transition

Can the PDFs be read in 2030, 2040, or 2050 if needed? Roy says that is a “hot” topic in the document management industry, with no clear answers. Some readers may want to look into the international, non-proprietary PDF/A format on their own, or inspect this list of validated software solutions that support PDF/A.

“Our focus was to get it electronic from the start,” Roy says. Ever the optimist, she believes the industry will shift (slowly) away from paper. “We’re looking at getting the whole lot electronic from the word go. Over time, people will move to the electronic and ditch the paper.” Naturally regulatory agencies will chart the course for such a transition, which will be interesting to watch.

Editor’s note: Phlexglobal expects to open a U.S. office in 2008. Roy is talking at the DIA’s Document Management eDM meeting in Philadelphia on Feb 6th. Her title: “TMF: The Decentralized Challenge.”