By Jennifer Goldsmith 

October 30, 2014 | Contributed Commentary | Time is money, and the cliché is never more apt than for life sciences companies seeking regulatory approval for a new therapy. In 2010, McKinsey & Company published a report which found mismanagement of trial master files (TMF) is responsible for slowing down trials an average of 12 months, costing a provider crucial revenue in the billions of dollars from an early market entrance.¹ 

Setting aside the staggering costs of failing to maximize sales opportunity, as regulators set the bar higher for SOP compliance and prepare their own systems for electronic submissions, the costs of maintaining a paper-based clinical TMF are steadily rising.

Now, with regulatory and competitive pressures mounting quickly, more life sciences companies are on the cusp of switching from what have been largely manual TMF processes and simple file shares to new, advanced eTMF technologies to enable paperless trials. In fact, one in 10 respondents to a recent Veeva survey said they are already leveraging purpose-built eTMF applications that include process-driven workflows and capabilities for managing trial documents and data electronically.² Further, the number of TMF owners actively building or evaluating eTMF applications to support efficient collaboration throughout a clinical trial study is up from 17% in 2010 to 33.6% today, according to a 2014 Drug Information Association (DIA) survey.³ 

In spite of this reality, over 85% of the industry is not yet using a purpose-built electronic trial master file (eTMF), according to Veeva’s research, with smaller organizations reporting the lowest rates of adoption. So what is preventing more drug developers from taking advantage of eTMF applications?

Getting everyone on board 

One of the biggest hurdles companies face when making the transition to paperless TMF is the creation of a collaborative system that all stakeholders in the drug development process can access easily and securely. The growing number of trial stakeholders (CROs, trial sites, agencies, committees, and patients) has increased the complexity of assembling reams of trial documents into a coherent package.

When stakeholders send documents via paper shipments or email, and maintain separate copies of TMF documents that they must reconcile at the conclusion of the trial, the burden of paper remains a significant drain on resources and efficiency. By contrast, cloud-based eTMFs are easily and securely accessible by all parties. Sponsors can define more efficient processes upfront, maintain visibility throughout the trial, and help ensure the TMF remains inspection-ready at all times.  

Building a repeatable TMF framework involves reaching consensus on expectations from the beginning, to ensure all TMF stakeholders are aligned on what the TMF artifacts are called, when they are due, and who is responsible for filing them. In order to know what content is missing or late, all contributors must first understand what is expected. A repeatable framework sets these parameters at the outset, reinforces the collaborative process, and improves overall efficiency.

Standardizing a common nomenclature can harmonize the filing efforts of diverse stakeholders. When multiple parties refer to items by different names, filing and tracking become confusing, increasing the chance for error. The DIA’s TMF Reference Model creates a standard nomenclature based on input from hundreds of pharmaceutical companies, CROs, regulatory agencies, and vendors across the globe. In addition to providing industry standard language and naming conventions, this model introduces new guidelines for content, structure, and metadata. For these reasons, more clinical trial sponsors are leveraging this model to build their own repeatable framework. 

Avoiding non-compliance 

With increasing regulatory pressure on life sciences — including new demands for remote monitoring of trial master files — organizations are seeking ways to improve inspection readiness and make TMFs accessible to auditors on demand. To meet the growing expectations of health authorities globally, organizations are rapidly adopting cloud-based eTMF applications in the same way that they once moved from paper case report forms to electronic data capture. These applications allow TMF owners to define standard operating procedures (SOPs) for how any clinical document is managed, and therefore flag mismanagement early. The eTMF owner can codify their SOPs within system workflows to identify non-compliant processes before the TMF is put before regulators for approval.

A cloud-based eTMF also easily accommodates the needs of health authorities, which are increasingly seeking electronic access to the TMF both in the US and globally. Most recently, the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has tightened its regulations to include ready TMF accessibility — a difficult objective to meet with a local or file-share TMF system dependent on paper. The MHRA tightened its parameters on the TMF after repeated inspection delays: in 2013, 33% of commercial sponsor inspections required extra days due to an incomplete or inaccessible TMF. Other regulatory authorities globally are likely to follow the MHRA’s precedent, putting more scrutiny on TMFs worldwide.

The cloud’s anytime availability and universal accessibility solves this challenge and greatly improves inspection-readiness. Eldin Rammell, a clinical records management expert and managing director at Rammell Consulting, said, “In the face of MHRA’s updated definition for critical findings, it is encouraging that organizations utilizing eTMF applications are experiencing significant benefits in inspection readiness and business efficiency gains.”

The urgent need for greater visibility into study conduct and quality benchmarks for trial operations is driving the industry’s growing use of new technology. The closer life sciences organizations come to collaborating on a single source of shared electronic documents, the more efficient and effective the drug development process becomes. Small organizations tend to be slower to adopt eTMF technology and processes, yet the benefits could be a tremendous boon to smaller companies that cannot afford the pricier content management systems often found in Big Pharma counterparts. CROs, too, lag but these critical clinical partners could stand to gain the most. Veeva’s benchmarking survey reveals that forward-looking CROs already leveraging advanced eTMF technology achieve more cost savings (63%) than sponsors (51%) and higher benefits.

Jennifer Goldsmith is the Vice President of Vault Strategy at Veeva Systems. Over the last 25 years, Jennifer has worked closely with industry leaders including Johnson and Johnson, Pfizer, Shire, BMS, Roche; and with technology pioneers such as IBM and CSC. Jennifer implemented some of the first regulatory submissions document management and publishing systems in the mid-1990s and has continued with a focus in clinical content management as standards have evolved. Jennifer is recognized for her expertise, named to PharmaVOICE’s Top 100 Innovators of the Year in 2012 and widely published in most life sciences trade publications. 

¹ McKinsey & Company, Trial Master File Management: Emerging Trends and Best Practices, by Jerel Davis, Edd Flemming, Gary Mao, Lawrence Wal and Rachel Zhang. 2012.

² Veeva Systems, “Veeva 2014 Paperless TMF Survey: An Industry Benchmark,” September 2014. Available at Veeva 2014 Paperless TMF Survey: An Industry Benchmark 

³ Redding K., Mulcahy L. Trial Master File Reference Model. Available at: www.diahome.org/en/News-and-Publications/Publications-and-Research/EDM-Corner.aspx. Accessed April 5, 2014.