The Trial Master File (TMF) has evolved from a repository of documents at the end of a study to an integral cog in the regulatory journey. This has led some companies to shift their perspective from solely meeting their compliance obligations to recognizing the TMF as a valuable company asset.
Rather than a burden carried by the study team, the TMF is being recognized for the wealth of information it provides, making its maintenance and management ever more critical. While some companies have a dedicated TMF team, others seek support from Contract Research Organizations (CROs). The quality of that partnership has the power to not only transform the TMF but strengthen other key areas of each partner organization.
In a joint white paper, “The Regeneron-Phlexglobal Collaborative Model for TMF Continuous Quality Improvement,” Regeneron and Phlexglobal share a blueprint for a strong partnership that has trust, openness and genuine collaboration at its core. This model is further explored in the webinar, “TMF Coffee Chat: Secrets to a Collaborative Model to Improve TMF Management.”
Changing the playing field
The quality of the Phlexglobal-Regeneron partnership has produced tangible results that we continue to build on as our collaboration strengthens. With ongoing support from Phlexglobal, Regeneron has been able to:
- Improve TMF quality, completeness and timeliness to help ensure ongoing inspection readiness
- Develop and implement process innovation that increases efficiency and frees busy study teams from repetitive work
- Create a “virtuous circle” of continuous improvements in TMF management overall quality
- Utilize jointly developed metrics and regular reviews to shape engagement with CRO partners and develop solutions to improve quality and process efficiency
The open and honest journey our two organizations took was integral in overcoming obstacles – be those people, process or technology.
Identifying the issue
Like many companies, Regeneron once had all members of the clinical study team – including CROs, vendors and Regeneron staff – uploading their individual documents to the Trial Master File. With around 2,000 people inputting documents and often in different ways, Regeneron sought to streamline the process to secure the quality and integrity of the TMF.
Phlexglobal was brought in to oversee a centralized approach to the processing and indexing of each document, and apply metadata to provide better quality, completeness, and timeliness. Outsourcing this work also freed up Regeneron’s study teams to focus on daily tasks, rather than be concerned about where to place each document in the TMF.
The paradigm shift
While the relationship was initially transactional, with Phlexglobal providing a valuable service to Regeneron, over time it developed into a genuine partnership. This was made possible by the approach we took from the outset. Both organizations were dedicated to meeting strategic goals and objectives through mutual respect for each party’s needs and perspectives. We worked together to fully document TMF requirements and define the best ways to reach set goals.
In addressing, as partners, the “big three” components that underpin a healthy and inspection-ready Trial Master File – quality, completeness, and timeliness – we moved away from the kind of comments that began with “you should...” to those that demonstrated our collective ownership of the process, such as “how do we best solve this challenge?” We approached problems together, rather than the sponsor mandating “this is what you must do.”
Shared core values
Regeneron chose Phlexglobal as the centralized TMF service provider based on their expertise and shared philosophy about the TMF and its impact on overall study success. Crucially, Regeneron also determined that Phlexglobal was the best fit for the core principles of openness, understanding and clarity. It is these shared values that have underpinned the partnership’s success.
- Complete openness and transparency
We have a shared appreciation for the intrinsic value of transparency in a business relationship. This open and honest foundation has enabled us to build trust, which is critical to a successful partnership. The level of engagement we have developed serves as an example to others within Regeneron and Phlexglobal of the benefits in sharing goals and priorities, Equally, it gives people across both organizations greater confidence to raise any concerns before they become major issues.
At the start of our relationship, for example, we spent time documenting TMF requirements and processes that were then translated into the Phlexglobal customer conventions. When it became clear there had been a misunderstanding about Regeneron requirements, we were able to have the kind of frank discussions needed to streamline and correct the process. This led to an easier format for customer conventions and a clearly defined process to confirm understanding of requirements, now and into the future.
- Collaboration with deep understanding
We have ensured real and effective collaboration by embedding practices such as joint goal-setting and brainstorming ideas to improve our combined work process. Each TMF lead, for example, sits on several different clinical study teams so they can gain a better understanding of the challenges and successes.
Our willingness to be vulnerable in our engagement has also helped us gain a deeper understanding of each other’s goals, needs and priorities and how we could align those with capabilities.
We drilled down into areas for improvement and developed solutions, including holding education sessions with CRO partners and study teams, stressing the importance of getting a good quality document into the TMF from the outset.
Organized monthly metrics assessments provided ongoing insight into issues such as study level rejection rates and enabled us to review defined quality KPIs at the granular level. For example, if an artifact kept coming up, we took a closer look at the queries around it and how we would address it so that the same problem did not recur. This level of detailed analysis and, crucially, action led to an impressive 50 percent improvement in defined quality KPIs in the past year.
- Clear roles and responsibilities
For a partnership to be effective, each member of the team needs to be clear about their roles and responsibilities. It is also about respecting the different layers of our partnership, which means getting out of the way of respective subject matter experts (SMEs) and enabling them to create a direct line of communication. This has ensured team members are comfortable about reaching out with a question or urgent need and nothing is overlooked.
For example, for many years Phlexglobal provided TMF completeness heatmaps of individual study TMFs to the study team to increase understanding of their status and identify potential issues to address. When it became evident that the original format was no longer efficient, Phlexglobal heatmap specialists worked with Regeneron heatmap owners to simplify the format and make it more visual. This updated heatmap is now used in various pilots, with positive feedback.
Where gaps are identified in knowledge, we have worked together to bridge them, ensuring stakeholders have the appropriate training. Over the past year we have fully resourced a team of SMEs to support study team compliance and adherence to global regulations.
A winning application
While the right expertise is essential, the quality of the partnership comes to the fore in the application of that expertise. We come to the table as one team without individual agendas. There is a genuine desire among all team members to find the best resolution for greater success.
This collaborative approach has enabled us to look at the bigger picture, too. Phlexglobal is taking an innovative approach to AI built on their TMF knowledge and experience, and we are examining how automation and machine learning can assist with challenging areas that continually raise queries. We are always exploring opportunities to make people’s lives easier so that rather than worrying about the TMF, they see it as a tool to be used whenever it is needed.
Whenever we implement any new workflows or processes, from AI to heatmaps, there is always a pilot because we want to get it right. We bring in the right people who support that part of the project to ensure their expertise is incorporated. Clear communication at the outset is a key component of effective collaboration.
What began as a joint venture to streamline the TMF process has developed into a symbiotic relationship that inspires innovation. Pivotal to the growing strength of the partnership is Phlexglobal’s willingness to explore all options in addressing requests or problems, adapting to changing circumstances and drawing on a deeper understanding of Regeneron’s TMF requirements. This open, honest and genuine collaboration has had a positive influence on other aspects of our organizations, including:
- Strengthening cross-functional engagements
- Improving onboarding and training requirements
- Refining vendor management procedures
- Sharpening the overall partnership quality framework model
The Phlexglobal-Regeneron partnership provides a clear blueprint for how we can be stronger together.
As a leading global authority in Trial Master File best practices, Phlexglobal helps trial sponsors and CROs worldwide improve TMF quality and oversight. To learn more, visit www.phlexglobal.com/tmf-services, or contact us today.
About the authors: Joanne Malia is Director of Development Records Management at Regeneron. Janice Cassamajor is Director of Customer Success at Phlexglobal.
Phlexglobal, Inc., a subsidiary of Cencora, Inc., provides Trial Master File (TMF) services and technology to the biotechnology industry. Regeneron is a leading biotechnology company that invents, develops, and commercializes life-transforming medicines for people with serious diseases. The information provided in this blog does not constitute legal advice and may include marketing statements. Phlexglobal, Cencora, and Regeneron strongly encourage readers to review available information related to the topics discussed in this white paper and to rely on their own experience and expertise in making decisions related thereto. The contents of this blog are owned by Phlexglobal and Regeneron.