Published in June 2015

Clinical Solutions
Copyright 2015 by PharmaLinx LLC

Contributed By:

MHRA Guidelines on TMFs –

WHERE ARE WE ONE YEAR LATER?
I
n April 2014, the UK’s Medicines & According to Franciska Darmer, former
Healthcare Products Regulatory Agency auditor with a global drug maker and who
(MHRA) updated its definition of a critical recently joined Veeva, early versions of eTMF
GCP inspection finding to include trial master systems were little more than electronic filing
files (TMFs) that were “not readily available cabinets. “Local file shares and FTP sites were
or accessible.” The agency asserted the change the go-to choice for many early adopters. Un-
was partly driven by the fact that more than fortunately, these systems lacked robust func-
one-third of TMF inspections are delayed due tionality, failed to process the vast volumes of
to incomplete or inaccessible files. In response, documentation associated with a clinical trial,
the global life-sciences industry heightened its and did not meet the accessibility require-
focus on managing its TMF content compli- ments of the inspection process.”
antly as part of a larger movement from paper Sponsors that replaced paper TMF files
to fully electronic trial master files (eTMFs). with such local network file shares did not JENNIFER GOLDSMITH
While the motivation driving the move to- foresee the resulting reporting and quality con- VP of Vault
ward eTMFs was undisputa- trol challenges. For example, Veeva Systems
ble, the technology landscape one of the biggest challenges
at the time was not structured MORE SPONSOR is that these systems often
to support increased regula- ORGANIZATIONS serve as a company’s central
tory and changing business repository for all clinical trial flows to ensure SOP adherence at all times
models. Since then, some AND CROS ARE documents and data globally. plus provide robust reporting for deeper in-
technology providers have ad- LEVERAGING Lacking any significant form sights into trial activity. Additionally, many
dressed these challenges by of configurable security, these enable easy remote access for inspectors and
evolving the eTMF from a ELECTRONIC TMF systems made all trial doc- auditors so documents can be reviewed as
static, end-of-lifecycle archive umentation visible without necessary from anywhere at any time.
APPLICATIONS TO
repository into an active, restriction, forcing sponsors to 2. Comprehensive trial documentation, with
in-process, accessible solution. INCREASE THE SCOPE create mirror files containing no incomplete or missing documents.
A year out from the MHRA just the relevant documents Quality control challenges drove many of
update, the industry is start- AND FUNCTIONALITY for inspectors. Even with this the MHRA’s frustrations with early eTMFs.
ing to make progress. More OF THEIR TMF. mirroring, inspectors often Documents were often stored in multiple
sponsor organizations and still had to wade through un- repositories and in different formats with
CROs are leveraging eTMF related trial data. little version control. Purpose-built eTMFs
applications to increase the scope and func- “To be inspection ready, sponsors must be today enable a single source of truth across
tionality of their TMF. able to quickly organize all documents related all parties to ensure all documents are up to
to the trial, and make them easily accessible date and in one location.
12 Months of Transition to inspectors,” Darmer continued. “In cases 3. Easy navigation with intuitive user inter-
where sponsors didn’t consider the external faces. Regulatory agencies typically rec-
While companies have started to make the usability of their eTMF, inspectors were forced ommend that their inspectors should be
move to next-generation eTMF solutions, vari- to navigate cumbersome filing systems and able to navigate a sponsor’s eTMF after no
ances in the design and sophistication of early thousands of unrelated documents, plus could more than one hour of training. However,
systems help explain the MHRA’s assertion not access trial documents in real time.” it was often taking frustrated inspectors
that many TMFs failed to meet inspectors’ ex- days to dig through complicated systems
pectations for accessibility and completeness. The Next Evolution and irrelevant documentation. A familiar,
When Veeva Systems surveyed more than 250 consumer web-like user interface allows for
TMF owners last spring in the largest eTMF To improve the inspection process, spon- quick training and navigation as simple as
survey to date, it found that over half of the sors and CROs have begun moving to pur- shopping online.
organizations using eTMFs reported working pose-built, cloud eTMF solutions. In fact, five 4. Rich insights to improve operational ef-
with either a local file share system (26%), of the world’s largest drug makers and half of ficiency. Simple file shares and generic
or a cloud file share such as an FTP site or the leading CROs now rely on next-generation content management systems are unable
dropbox.com (18%). More than one-third of systems to meet four key requirements: to provide critical insight into the clinical
respondents reported using generic content 1. Continual inspection-readiness and un- development process. Purpose-built eTMF
management systems like EMC Documentum limited accessibility. Without robust func- systems, in contrast, capture process- and
or Microsoft SharePoint to store and share clin- tionality, early eTMFs had no built-in con- quality-specific data. Real-time reporting
ical trial documents, whereas only 13% had trols and document review only occurred at leverage this information to provide organi-
implemented a life sciences-specific eTMF. study end. Today’s eTMFs automate work- zations with an in-process view of the trial.

37 June 2015 ● PharmaVOICE

 Clinical Solutions

Nigel Jones, VP of Global Clinical Devel- ceutical company, said its new eTMF system “In the past, our auditors were used to
opment at TFS, a full-service CRO, believes provided the rapidly growing company with enduring a 48-hour-or longer wait for a box
the simplicity and accessibility of cloud-based a single platform on which to collaborate to arrive from off-site storage, only to find that
eTMF systems have become a pre-requisite for with partners efficiently and ensure inspection it didn’t contain the desired document,” Fate
doing business with global drug makers. “The readiness at all times. “Since adopting a cloud described. “Today, the correct documents are
majority of proposals CROs submit today eTMF, we’ve been able to shave at least 40% retrieved in seconds. With our cloud eTMF,
include some form of eTMF support,” he said. off the time needed to reconcile TMF docu- my audit teams are travelling less, and spend-
“We invested in a robust, accessible eTMF ments at the conclusion of a trial. Now, we ing more time ensuring quality and analyzing
solution to support our expansion across con- have full visibility and can track the status of trial effectiveness.”
tinents, and have since realized the cost and the TMF in real time for the entire duration of
time savings that come from a streamlined, the study,” Fate said. New Reporting Guidelines Drive
automated system for sharing and storing all Even before the MHRA issued its guidance Life Sciences Forward
trial documents,” Jones continued. “In the to simplify eTMF navigation, one of the big-
past, our project managers could spend weeks gest challenges that sponsors and CROs faced Sponsors, CROs, and health authority in-
working with a client to prepare the TMF for when implementing an eTMF was getting spectors all have similar goals: to be able to
inspection. Now our researchers use the time people to use it. Typically, eTMF and content access the TMF easily, whenever and from
they used to spend chasing documents to act management systems proved overly complex wherever they are. Cloud technology provides
on trial data, rather than just collect it.” and cumbersome to navigate. Over the last this type of ubiquitous access, but when also
Many first-generation eTMFs were built year, more sponsors have started implement- linked innately to clinical processes, the TMF
around “electronic filing cabinets” that still ing improved eTMF systems with simplified becomes more than just an electronic record.
retained paper-based processes, such as print- operations to satisfy inspectors’ ease-of-use Fully unlocked, next-generation eTMF solu-
ing and scanning documents. Consequently, requirements. tions can be strategic assets that not only dra-
sponsors, CROs and inspectors found these Now, using an eTMF is becoming a natu- matically improve the inspection process, but
early systems did not deliver the benefits of a ral part of the clinical trial process workflow, also offer sponsors the type of insights within
truly paperless TMF. “The entire trial process ensuring study findings are reported as they and across trials that drive long-term improve-
is rapidly moving away from paper,” Jones happen and status reporting is more accurate ment for clinical programs.
observed. “Today the majority of clinical trials and effortless. Real-time insight into trial The industry has had a year to digest the
are done with electronic data capture to save progress allows the entire team to finally col- MHRA’s updated definition of a critical GCP
the data entry step and enable the collection of lect data throughout studies, and use that data inspection finding as it relates to the TMF,
important trial performance data.” to make better decisions about commercial pushing a growing majority of companies to
To support the paperless model, next-gen- strategy and therapy effectiveness. Over time, adopt operational and technology strategies
eration eTMF systems offer electronic processes data-driven trial optimization will result in to meet or even exceed the MHRA’s expec-
for information sharing and storage. Individu- more efficient trials and faster time to market. tations. The switch to solutions that support
als no longer send paper to a central records Some forward-thinking organizations are global compliance, as well as improve overall
management team. Rather, the responsibility already unlocking the benefits of TMF metrics. study efficiency and effectiveness is likely to
for filing documents into the eTMF is distrib- In the Veeva 2014 eTMF survey, the compa- continue not just to meet health authority
uted across the clinical ecosystem, making it nies that reported extensive use of performance requirements, but also to bring potentially
critically important to assign and communi- data saw markedly more benefits from their life-saving products to market faster. The suc-
cate ownership of TMF documents. When all eTMF systems than those that did not col- cess these pioneering organizations are achiev-
parties have defined roles in the study SOPs, lect metrics. For example, these organizations ing could have a significant impact large
sending files electronically and ensuring task noted improved document quality (63% ver- influence on the shape of study management
completion is quick and efficient. sus 29%); greater audit and inspection-read- and the clinical technology landscape for years
In particular, cloud-based solutions are iness (56% versus 25%); easier collaboration to come.
well-suited to support this type of paperless with sites (54% versus 32%); and, increased
environment as they offer the highest level SOP compliance (49% versus 16%). Editor’s Note: To download the Veeva 2014 Pa-
of collaboration across a diverse set of par- Kythera’s eTMF solution now allows the perless TMF Survey: An Industry Benchmark,
ticipants. Sponsors ensure consistency and internal auditor to regularly run a full range October 7, 2014, visit http://www.veeva.com/tmf-
adherence to process controls by creating doc- of standard and ad hoc reports, giving a more survey-2014.
uments directly in the eTMF system. With accurate view of trial progress. According to
multiple parties submitting information to Fate, “When everyone has visibility into the
the TMF remotely throughout the lifecycle of reports, it removes a lot of questions at meet- Veeva Systems Inc. is a leader in cloud-
the trial, automated standards are in place to ings and with our CRO. We are all spending based software for the global life sciences
ensure quality up front. Missing documents less time meeting and more time working.” industry. Committed to innovation, product
are brought to sponsors’ attention throughout Automated filing and accessible data shar- excellence, and customer success, Veeva has
the trial, and incomplete documentation is ing systems mean that internal auditors have more than 275 customers, ranging from the
identified early in the process and sent back to the opportunity to redefine their role and do world’s largest pharmaceutical companies
the study team for immediate correction. The more with less. Cloud eTMF solutions allow to emerging biotechs. Veeva is headquar-
result is a TMF that is always inspection ready. auditors to manage the quality of a TMF re- tered in the San Francisco Bay Area, with
Renee Fate, a senior manager responsible motely and in real time, ensuring compliance offices in Europe, Asia, and Latin America.
for document management at Kythera Bio- without the need to visit multiple sites and For more information, visit veeva.com.
pharmaceuticals, a clinical-stage biopharma- spend weeks at a time on the road.

PharmaVOICE ● June 2015 38