Nothing may invoke fear in the heart of new, or even seasoned, regulatory project managers more than the preparation and submission of a marketing application in eCTD format for their company. At first glance, marketing application submissions can appear to be a tedious effort to manage with hundreds of documents and players, and requires orchestrating intricately detailed timelines and intertwined steps. A successful filing is possible but requires beginning with the end in mind by planning for and organizing the application's contents and process steps and creatively managing timelines to fully utilize existing resources. A successful regulatory filing also requires involvement and approval at the onset and throughout the execution of the project from all necessary stakeholders - including the CTD medical writing team, document reviewers, corporate management, marketing experts, and the regulatory operations team. Contractors or necessary third-party vendors should also be included in the project planning process as including them in later stages of the project execution can result in missed submission timelines.
Extensively planning a project to formally initiate processes in creating an eCTD application may seem like an imposing amount of time and money spent up front. However, if a solid project management foundation is built at the very beginning, it will save time and money in later stages. By planning before processes begin, challenges that could impact the eCTD's completion can be limited or avoided. Project management challenges of creating an eCTD marketing application can span any and every discipline of the project, from authoring to reviewing the compiled submission, and may include:
Without diligent oversight, these challenges can jeopardize the successful execution and submission of the application. Planning with the end in mind also enables rapid response and smooth integration of change as it occurs because a clear, organized, and detailed plan allows for quick adjustments.
Consider this scenario: you are a project manager at a small pharmaceutical company and this marketing application is the first eCTD for your company. Your regulatory submissions team is inexperienced in compiling eCTDs, and your medical writing staff consists of only a few people, so the eCTD application will require outsourcing the majority of the authoring work to a CRO, which can leave you feeling out of control of those resources. You have half the budget of what you think you will actually need and scheduling delays continue to occur before the project is even initiated but the final submission deadline cannot move in order to meet a corporate milestone.
Hopefully only parts of that worst case scenario sound familiar, but regardless, the best plan to ensure a successful filing. no matter the situation, is to handle these types of challenges proactively to reduce their impact on timelines, budget, and overall quality. Two of the best tools to aid a project manager with eCTD submissions are based on fundamental project management concepts of balancing time, cost, and quality constraints: an integrated table of contents to track and manage the project's progression and a rolling submission management strategy to maximize resources and timelines.
The idea may sound elementary, but a basic and inexpensive spreadsheet works effectively to plan the contents and map the processes required in preparing an eCTD application. First and foremost, the spreadsheet will serve as an outline for the contents and granularity of the application. Then, by integrating the steps each granular document will progress through (from authoring to final submission), the spreadsheet's utility is further expanded to manage document progression, track issues with a particular document, and even track assigned resources responsible for a granular section. An integrated table of contents in the form of a spreadsheet can also serve as a powerful communication tool between different functional groups within the company and across outside vendors. For example, by sharing the integrated table of contents with the regulatory operations team that will compile the eCTD, the project team can easily denote how the document file names should be displayed in the eCTD and provide notification on which sections are ready for publishing into the submission.
By using a spreadsheet format to outline and track the contents of the application, a project manager has the flexibility to easily customize the organization to best suit her needs. For example, one may find that splitting the contents into smaller worksheets within the same spreadsheet file may be more useful; one can group sections by CTD module, by completion deadlines, or by the department responsible for creating particular sections. In addition, if the eCTD application includes a complex Module 3 with multiple drug product or drug substance sections, those could be split into separate worksheets to reduce confusion in referencing and tracking them. Because a spreadsheet is a commonly-used software application, it allows for quick and easy communication between many different departments and vendors in a format that is easily understood by all people.
Once an integrated table of contents has been developed for an eCTD application, it is important to keep in mind a few points:
Another tool in effectively managing the preparation of an eCTD application is to plan and execute the project in a rolling fashion, or divide it into smaller portions based on completion timelines and functional areas, even if the application will not be submitted to the regulatory agency in rolling units. By organizing the eCTD's creation in a rolling fashion, the project team is able to maximize utilization of existing resources, achieve high quality and consistency throughout the application, and reduce the effort required to manage the application since it will be accomplished in pieces. If resource allocation and schedule are planned to maximize existing resources at the beginning of the application process, the need for additional outsourcing and costs at later stages can be reduced or even eliminated. In addition, using the same group of resources maintains excellent quality and consistency from the authoring stages to the final submission publication because the same group of resources can be thoroughly trained, and be consistently involved with related sections of the eCTD.
Building an eCTD submission as a rolling submission can begin as soon as the first submission-ready document is available from the medical writing team, rather than waiting to initiate the submission process until all documents are finalized. Being the final step in a multi-step process, all too often the timelines for the regulatory submissions team are condensed to make up for timeline slips during earlier phases in the project. Condensing such a large effort into a short time frame at the very end requires an overextension of regulatory submission resources and introduces opportunity for delay and error. Put simply: if work can be done ahead of time, do it early. By staggering the preparation of the eCTD into rolling units, a thorough quality control review of the entire eCTD can be performed as portions of the application are completed instead of waiting to the very end of the process, again introducing the possibility for delay and errors when they can have the greatest impact on the final submission deadline.
If a rolling submission management strategy is followed, remember that once documents are finalized through authoring, review, publishing, quality control reviews, and the final approval cycles, then consider the document final for the actual submission. No matter how tempting, do not make further changes after the eCTD application has moved on to the next step or to the next rolling unit of sections.
Always remember that planning is essential to minimize risks introduced along the different stages of the project and will increase your chances of a successful eCTD filing. The processes and project management strategies developed in the planning stages such as an integrated table of contents, or a timeline for a rolling submission strategy, will carry you and your project team through the project's execution. However, as the project progresses, review and update your processes and tools as project change requires — you will need to evolve as the project progresses to maintain efficiency in managing the project. These project management tools are there to help, not hinder, the process. Use what works most effectively for your management style and your team.
Rachel L. Cooper is a project manager at Cato Research for a variety of drug development activities, including clinical trial management activities, regulatory strategy and compliance, paper and eCTD submissions. As a project manager for both drugs and biologics at all stages of drug development, from the early IND stage through marketing applications and post-marketing procedures, she has extensive experience preparing and managing submissions in the eCTD format and labeling in the SPL format. Ms. Cooper has also managed clinical trial preparation, conduct, and termination activities from site selection through preparation of the clinical study report and has experience managing the development of meeting requests, briefing packages, and meeting strategy for numerous interactions with the FDA. She is also responsible for facilitating activities of one of the project management departments at Cato Research, including creation and maintenance of company infrastructure processes, tools, and training related to project management and she directs supervision of project management personnel. Rachel can be reached at 919-361-2286 or via e-mail at firstname.lastname@example.org.