Managing Regulated Content Enterprise-Wide

March 13, 2015
Kythera content management platform shaves TMF reconciliation time by 40 percent

Kythera is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel prescription products for the aesthetic medicine market. The company’s objective is to develop prescription products using an approach that relies on the scientific rigor of biotechnology to address unmet needs in a rapidly growing market. Kythera’s initial focus is on facial aesthetics — the market’s largest segment. The company’s drug for the reduction of submental fat is currently in late-stage clinical development.

Kythera sought a system to improve clinical document management and facilitate business processes for the development of its newest product candidate. The company had 26 studies already on file along with four active clinical studies, resulting in thousands of documents to share, manage and store. Kythera had been using a patchwork of different document repositories and systems for each functional area, including a file share system for TMF documents and a SharePoint-based system that was difficult to access and use for internal collaborators and external partners. Multiple versions of documents changed hands with no reliable document accountability. The resulting errors slowed study processes and added risk. Exchanging documents by couriers internationally only added to the inefficiency.

Kythera’s legacy system was also extremely difficult to manage and update. Modest internal IT resources meant Kythera required a turnkey system that integrated clinical, regulatory and medical affairs document management and didn’t require extra staff to implement and maintain. Renee Fate, Kythera’s senior manager of document management, already familiar with cloud technology knew that a multitenant cloud-based solution would be easier to update and maintain remotely.

Preparing for rapid growth and facing increased volumes of content, Kythera needed to select a solution without delay. After evaluating vendor offerings Kythera decided to trial then implement Veeva Systems’ cloud-based Vault, an end-to-end regulated content management platform built for the global life sciences industry, supporting business-specific applications and connecting workstreams across clinical, regulatory and medical affairs. The new solution would also link with Kythera’s promotional materials management system.

“We looked for an enterprise-wide solution that could effectively serve diverse masters across the business — regulatory, CMC, clinical, sales and marketing, HR, finance and legal — with different requirements for user knowledge, compliance and security,” said Jeff Webster, Kythera’s COO. “Vault was the right solution for us, given its intuitive interface, its functionality across Mac and PC platforms, mobile access, its full complement of 21 CFR Part 11 compliant capabilities, and the security and backup features necessary for our most important asset: our content.”

Fate added, “As a growing company without an IT team, we needed a cloud environment. With Veeva, we have no servers to manage, updates are pushed out automatically — without any disruption to our teams, and our mobile workforce can access the system from anywhere in the globe, with any device.”

Kythera rolled out Vault eTMF to manage all of its trial documents and support global collaboration between sponsors, CROs, sites and investigators with its integrated Investigator Portal. The company is also leveraging Vault Quality Docs to establish a single source of truth for all quality documents, and Vault Med Comms to simplify the global coordination of medical communications.

According to Fate, “Over the years, I have always received the same feedback from users: ‘We want more visibility, with information available in real time.’ Veeva Vault delivered on all fronts and was validation-ready, which makes my life much easier. Feedback has been very positive.”

Kythera has established Vault eTMF as its central hub for exchanging documents with CROs, investigator sites and other clinical partners. Each exchange is tracked by Vault and available via real-time reports that provide visibility into trial status and TMF completeness. The resulting data also provides actionable insights that allow Kythera to proactively improve study processes.

Currently, Kythera has more than 100 Vault eTMF users with plans to expand further with each new study site. The new solution brings Kythera a wide range of advantages, including:

Improved Workflow – Vault delivers total electronic access to documents that were previously transmitted as email attachments or as paper copies via courier. For Kythera, this has improved workflows throughout the trial process. For example, protocols authored by the medical writer are now uploaded directly into Vault, automatically notifying the requisite six or seven reviewers. The reviewers can make comments simultaneously in real time, and then the editor can consolidate, obtain final approvals and publish to Vault, helping Kythera move more quickly and reduce cost.

Electronic Signature Capture – Kythera is now able to capture electronic signatures and is building new SOPs to take full advantage of this time-saving convenience. “Historically we collected many more signatures than the government requires, adding a lot of inefficiency to the process because everything gets stalled while we wait on those signatures,” noted Fate. Electronic signatures will prevent needless delays in creating submission ready documents.

Timely eTMF Reports – Vault eTMF allows Kythera to run a full range of standard and ad hoc reports, giving them a view into trial progress and enabling better management of the study. The company uses Vault’s expiry report to alert team members before documents expire. Manually tracking expiration dates, due dates and receipt confirmations takes an enormous amount of time. Everyone on the Kythera team is happy to have Vault automate that work. A site document report shows the study documents on file for site and a site initiation report shows the status of documents for that milestone.

“When everyone has visibility into the reports, it removes a lot of questions at team meetings. We can spend less time meeting and more time working.” Fate said, “The best part of Vault’s reporting is that I can pull my own reports. I don’t need to ask IT or get special training. I can easily run custom reports to answer questions as they come up. If you haven’t had that before, you might not realize how wonderful it is.”

For Kythera, the biggest change has been transitioning from a predominantly paper-driven TMF system to an electronic system. The company has taken the time and attention needed to ensure a successful changeover — analyzing and homogenizing its taxonomy, creating helpful classification “cheat sheets” for users, developing new SOPs, and integrating new electronic processes into daily workflows. Vault eTMF’s close alignment with the industry-approved Drug Information Association (DIA) TMF Reference model and consumer-like interface have also helped the conversion to a paperless system go smoothly. “Vault is easy to use for a fairly painless transition that might have otherwise overwhelmed us,” added Fate.

Kythera’s Vault eTMF, first step towards paperless trials, is helping the company speed study start-up, enhance visibility into trial operations, ensure documents are organized in a common structure for easier search and retrieval, and collaborate more efficiently. Now, Kythera can securely exchange documents with all authorized study participants, including auditors to support inspection and remain audit-ready at all times.

Survey Says

With the increased focus on TMF quality from the Medicines and Healthcare products Regulatory Agency (MHRA), the benefits from going paperless for audits and inspections carry additional weight. The MHRA recently found 35 percent of commercial sponsor inspections required extra days to accommodate incomplete or inaccessible TMFs. As such, the MHRA has updated their definition of critical GCP inspection findings to include a provision for TMFs that are not readily available or accessible, or are sufficiently incomplete that inspectors cannot successfully carry out their duties. As such, 33 percent of respondents to the Veeva 2014 Paperless TMF Survey: An Industry Benchmark report expects to provide auditors with remote access to an eTMF by early 2015 and an additional 12 percent with no clear timetable indicated they would provide remote access “as soon as they have the technology.”

Today, only 43 percent of source documents are created electronically (on average across trial parties including sponsor, CROs, sites, IRBs/IECs), according to Veeva’s study. The use of paper and electronic file systems to manage the TMF contributes to the industry’s continued reliance on manual processes as the survey reveals that email (69%) and paper (57%) remain the predominant means of exchanging trial documents. As Kythera has discovered, the industry needs to adopt a paperless operating model, leveraging the eTMF across all clinical participants to execute trial management activities from planning, through conduct, to completion. Only then can sponsors maximize their eTMF systems, fully optimizing process efficiency and maintaining inspection-readiness at all times.

According to Kythera, the greatest benefit to its new system was the speed and efficiency gains that accompany going paperless. Paperless processes resulted in numerous efficiencies such as faster site start-ups with real-time review of all documentation and expedited approvals. Because everyone can access the system at any time, the processes keep moving regardless of the participating individuals’ physical location. Moreover, the easy access and powerful search capabilities of a cloud-based electronic system offer a vast improvement over Kythera’s prior experience with paper documents. Often, teams endured a 48-hour-or-longer wait for a box to arrive from off-site storage, only to find that it didn’t contain the desired document. Today, the correct documents are retrieved in seconds in Vault eTMF.

Versioning documents through Vault ensures every member of the team is accessing the most recent copy, reducing errors and ensuring that work is not duplicated. All users’ interactions with the content are automatically tracked by the system, so everyone has visibility into changes and updates. Vault also helps Kythera protect their information. “Our people tended to keep everything in email, which was risky,” noted Webster. “When someone left the company, any information or document maintained by that employee was basically gone. No one goes through an old archive to find a file. Now, company information stays accessible.”

With Vault eTMF, documents are filed, QC’d and approved throughout the course of the trial, saving time at study close, according to Fate. “It’s much harder to look for information at the end as opposed to making changes along the way. Now, we can identify missing documents as they occur rather than find ‘surprises’ at the end which force us to back-track and waste time,” Fate continued. “Document reconciliation can take months of work. To do this in real time would save 40 percent of my time at study close.” Plus, auditors get immediate, remote access to the appropriate documents within an intuitive system that requires minimal training.

For Kythera, converting to an electronic system meant re-imagining prior business processes and eliminating the reliance on paper in order to fully leverage the new solution’s capabilities. “We’ve had to adjust the way we think — from a paper mindset to electronic. As an organization, Kythera cannot adopt an advanced system like Vault while maintaining old processes. To fully leverage Vault’s capabilities, we had to make changes from the ground up like revising many of our SOPs in parallel with deployment,” said Fate.

“The biggest issue when it comes to transitioning to a new system — and letting go of paper — is the fear of losing control. But, when employees and partners see the increase in efficiency that comes from a more streamlined, repeatable process, they are more likely to embrace the system and accept a new digital business environment,” concluded Fate. “Veeva Vault has made this transition much easier than expected because users are enjoying many benefits that improve their daily work, increase performance and enhance productivity.”