Leading a marketing application as the submission lead
A marketing application is led as a whole, from the regulatory strategy to the published dossier, by a submission lead who, with the regulatory lead, holds a large cross-functional team together, enables its work through five stages, anticipates the risks every submission meets and draws on experience of whole submissions to do so.
The marketing application and its team
A marketing application represents the end result of years of development, significant financial investment, months of work and the collaboration of a very large cross-functional team, and it is a significant milestone in any product's development. Regulatory submissions are complex and each has its own characteristics and challenges, and new regulatory guidelines across regions and new innovative therapies and digital tools have added complexities that require dynamic planning, close coordination and effective project management. Whatever its form, every marketing application requires input from a broad cross-functional team and a large and diverse collection of source data and reports supporting the proposed product and its labelling to gain approval, and a successful, high-quality one requires a well-balanced team from regulatory, commercial, chemistry, manufacturing and controls, nonclinical, clinical, medical, statistics, programming, data management, safety, medical writing and other fields. With so many individuals and areas of expertise involved, communication becomes critical.
The submission lead
A clearly identified overall lead, the submission lead, and a lead for each function are key to the team's functioning and delivery, each overseeing and managing the people in their area, ensuring the open flow of communication to, from and within it, and serving as its primary point of contact. Every team needs a capable leader, and without a clearly identified and capable one, miscommunication and chaos can ensue. Like any large team effort, a clearly defined lead role and agreed processes are critical to a high-quality, on-time marketing application that is accepted for review and ultimately approved. The submission lead is essential to enabling the team's work and to addressing all of the challenges and risks that typically arise during development of a marketing application, and fulfils a critical role that requires a daunting array of skills, including interpersonal and communication skills, project management, extensive drug development, regulatory and marketing application knowledge, and leadership. Beyond the skills for authoring or leading a single document, leading a submission requires extensive project management skills and consultant-level submission expertise, and effective, relentless and timely communication with all parties is vital, as are flexibility, securing consensus for any changes, and resolving issues as they arise.
Experienced regulatory and medical writers often have the array of skills the role requires and make excellent submission leads, whether they oversee only the writing activities or lead the entire submission team. In one practitioner account, regulatory and medical writers with submission experience are well suited to the role, whether they oversee all writing activities or lead the entire submission team. The account attributes this to every such writer having to interact with a broad range of functions to develop and deliver a document, be a good communicator and establish and keep to an agreed set of timelines, and to working in depth with both the underlying source data and the high-level messaging, interpretation and presentation. Much of the role may overlap with project management, and an experienced project manager is an essential part of any large submission team, but it is most efficient for someone who can speak to the data, the deliverables and the messaging to serve as submission lead. Fluency in the strategy and content of the submission lets the lead drive discussions and prioritise the team's activities and, most importantly, recognise the potential cross-functional impacts of each new development as the project progresses and ensure the necessary parties are brought together to address them.
Coordinating the submission team
The submission lead plays a key role in coordinating the submission team both internally and externally, reaching out to team members for information and status updates, conducting regular meetings to keep everyone informed, and establishing appropriate contacts with outsourced vendors for timely exchange of information. In conjunction with the regulatory lead, the submission lead:
- guides the team in developing a comprehensive eCTD content plan and strategy
- integrates the perspectives of functional areas, contributors and subject matter experts into cohesive messaging that meets regulatory requirements under the eCTD
- communicates the expectations of regulatory reviewers so that they are factored into the summaries and reports
- assists in authoring and reviewing documents to ensure consistent messaging and adherence to regulatory guidelines for the product label
- identifies and monitors potential risks to the submission, working with the team on contingency and risk mitigation plans throughout
The submission lead serves as the connector, providing strategic and tactical oversight throughout the process to ensure on-time preparation of high-quality documents.
The submission lead must be accountable and responsible to the submission team, wears many hats and ensures that the team is functioning well and communicating at all times. There is no such thing as overcommunication on a submission project, and submission teams need to keep the information flowing flawlessly. Leading and working with large multidisciplinary teams under tight timelines with complex results and interpretations is difficult, even for seasoned submission leads. Increasingly, more than one sponsor company and several vendors are involved, and contract research organisations delivering the clinical studies and other vendors supporting nonclinical work, chemistry, manufacturing and controls, statistical programming and analysis and other key submission components each play a supportive but crucial role. The submission lead must ensure that roles and responsibilities are clear, that communication flows across these organisations and that all activities are accurately tracked. Although the submission lead's role can be challenging, successfully leading a high-quality submission that meets its deadline and ultimately results in approval brings a huge sense of pride and achievement.
The five stages of a marketing application
Embarking on a marketing application requires extensive planning and is carried out in stages, and by enabling the work in each stage, from the initial regulatory submission strategy through publishing and submission, the submission lead ensures a comprehensive and cohesive application.
Regulatory submission strategy
The submission team, made up of the submission lead and the core team members, should be formed 9 to 12 months before the planned submission date to establish the overall goals and strategy, including the key messaging, the target product profile and plans for interactions with the relevant regulatory authorities. To ensure confidence in the proposed strategy and plans, the submission lead or the regulatory lead should review all previous interactions with the regulatory agencies, focusing on prior agreements and how they have been addressed. The standard of care and recent approvals for similar products and for any products in the proposed indication must also be identified and made available to the team. Team meetings begin at this stage with a formal kickoff meeting to ensure alignment on the goals and expectations, review a high-level timeline and define roles and responsibilities, and the submission lead should establish a regular cadence of meetings after it, perhaps monthly or biweekly, increasing to weekly closer to the planned submission date.
Key messages serve as guideposts for all content development and are important for the submission and the labelling, and many sponsors use storyboards, target product profiles, draft labelling, a core data sheet or other documents to build and capture them. A significant pitfall the submission lead must watch for is that these key messages are often aspirational and disconnected from the data, and these internal documents can also become formal documents that require time, effort and prioritisation from key team members and distract the team from preparing the actual submission documents.
Presubmission meetings with regulatory agencies are critical for successful submissions and are a key part of the submission lead's strategic input early in the project. A submission to several countries can greatly complicate planning and strategy, because the timing of each country's presubmission meeting and each planned submission date must be accounted for in the timelines. More importantly, the timeline and the content development of the documents must consider the potential for each country's regulatory authority to raise different, and sometimes conflicting, questions and requests during presubmission meetings. The timing of the data and briefing document that presubmission meetings require must be built into the timelines, as these activities may be on the critical path for completing drafts of key documents.
Timeline and content planning
The submission timeline must be detailed enough to confidently identify and track the critical path items. The content plan, which should account for the timelines and for every file in the submission, including datasets, case report forms and analytical method reports, is a critical living tracker reviewed with the team throughout the submission, and the publishing team tracks it closely to ensure each element is placed in the appropriate eCTD folder under regulatory requirements. Maintaining the timelines and content plan may fall to other functions, such as project management, but the submission lead makes certain that all groups have a voice and a seat at the table and that every activity and deliverable has been taken into account. Successful content planning and timeline development depend largely on knowing and identifying the dependencies within and across modules, from the obvious, such as study reports depending on final data and summary documents on well-drafted study reports, to the more nuanced, such as the availability of finalised chemistry, manufacturing and controls stability data, nonclinical SEND datasets, or a population pharmacokinetic and exposure–response report. Ideally the timeline and content plan are comprehensive and the team has considered some alternative scenarios based on unexpected data outcomes, study completion delays and regulatory authority feedback. This planning is a continuous process of maintaining an agreed plan and adjusting it to incorporate new developments as they arise.
Content development
In content development, storyboards, the target product profile, the draft labelling, a core data sheet or other documents serve as the source for key messaging and a reference and guide for all content. The submission lead enables the authoring of submission documents by championing a system for coauthoring and subject-matter expert review. By staying familiar with the data and reviewing documents for consistent messaging and presentation across the submission, the lead is able to advise and guide the writers and team. Throughout the process submission leads may also guide writers on consistency of messaging and presentation and on how to adjudicate difficult comments, assist writers with comment resolution meetings, and manage conflict resolution on complex issues. The submission lead is integral to enabling the transparency among disciplines that the modular structure of the common technical document requires, so that appropriate cross-references are included to locations with more detailed information.
Content finalisation
In collaboration with the functional areas, the submission lead ensures that the lists of reviewers and approvers are proactively defined and agreed under the sponsor's existing processes and governance, and before any reviews provides reviewers with training in best review practices. As part of developing the overall submission timeline, the submission lead or a delegate schedules reviews, comment resolution meetings and approvals. Critical to the success of these reviews and approvals is including approvers and any other external-party or upper-management reviewers as early as possible. Approvers, external parties and management seeing a document for the first time at approval is a recipe for disaster, regardless of the quality of their input.
Publishing
The submission lead plans for submission-level publishing in accordance with the content plan when developing the full submission timeline, and, working with project management and regulatory operations, ensures the content plan is used to track document publishing status, missing components and the final review and approval of the published submission. It is especially important to ensure that all supporting documents, such as report appendices, are included and can be linked. Although the publishing steps will always be the final steps of the process and are therefore rate-limiting to the submission, planning for them from the very beginning is key. The submission lead ensures the whole team has visibility of the time they require and that documents are published as soon as they become available.
Risks and their mitigation
All submissions will encounter roadblocks, even with perfect, comprehensive planning, and the key to a successful submission is anticipating the risks and creating an action plan to mitigate them, often by listing potential risks at the initial stage of planning so that an appropriate contingency plan can be developed. The risks and mitigations associated with marketing submissions include:
- Poor communication. Clear, open communication across the broad team is key to success and is usually accomplished through weekly submission team meetings with an agenda provided beforehand, minutes, an action items log, a detailed timeline with a dashboard, and a content plan; this is especially true for sponsors and their vendors but also for the core teams that enable decision-making. Personality challenges and conflicts can always arise, so standards of conduct and escalation paths may be necessary.
- An incomplete or disconnected team. At a minimum, a lead representative from each functional area is needed, and it is critical that these leads can communicate both with those outside their area of expertise and with experts in their discipline. Team dynamics make a submission pleasant or painful, so team members need to work together, value input and have time to dedicate to the program. Including several sponsor companies and vendors can make this more challenging.
- A lack of clear roles and responsibilities. Clear roles and responsibilities must be established, often with a responsible, accountable, consulted, informed chart, commonly called a RACI. A balance between reviewing outside one's own expertise and staying in one's lane is important to success and efficiency.
- A lack of oversight or engagement. A submission governance structure and a risk log are important, as is involving senior managers from relevant functions early. Getting it right the first time and avoiding late, drastic changes in approach and messaging can be accomplished by including approvers in draft 2 reviews or earlier. Detailed planning and early engagement with a core team containing the key functional areas is critical.
- Inexperienced team members. Mentoring inexperienced team members is an often-overlooked part of the submission lead's job. The best way to learn is by doing, and everyone has a first submission, or new role, and may need some guidance or oversight. The submission lead can guide or mentor others directly and find other experts to help. A clear sign of a healthy, high-functioning team is that less experienced members get the support they need.
- A timeline that is only high-level or incomplete. Developing and agreeing a realistic detailed timeline is important. The critical path must be clear, and each functional area must have visibility of more than its own timelines. Timelines are living documents that need to adapt as problems develop in executing the agreed timeline, and the submission lead works with other team members to keep them up to date and communicate any changes, and their ramifications, across the team.
- Poor budget and timeline management. However many contract organisations are involved, budgets of funds or time allocated to specific activities need to be tracked and adjusted as needed. Teams need to understand when additional requests for data analyses or extra document draft reviews will affect budgets and timelines and when they will not.
- Results that are not as anticipated. A priori contingency planning helps teams avoid derailment when results are not as expected, making it easier and quicker to select and implement alternative scenarios and adapt accordingly. The submission lead needs to drive the revisions and bring the key team members together to address the changes and agree on the path forward.
- Teams panic in a crisis. When submission teams are stressed and overworked, tempers can flare and details can be missed. It is perhaps the submission lead's most important responsibility to be the calm in the storm and move ahead, keeping everyone aligned and engaged.
Careful planning and coordination are vital to the timely submission of a biologics licence application or new drug application. Writing the submission itself can be relatively straightforward using prescribed guidelines, but many preparatory steps require cooperation from all team members, and if they are not properly thought out and managed, unforeseen difficulties and delays may ensue. Gathering input from and responding to requests from contributors, the timing of requests to external experts or contractors, performing ad hoc analyses, and waiting for responses from reviewers, who may have conflicting priorities, can all adversely affect project timelines, and such issues can be particularly detrimental for small organisations with limited personnel and financial resources. A proactive approach to planning every aspect of the submission process will enhance the quality of the document, ease the work of the contributors and keep the project on track.
One team's experience of a biologics licence application submission points to the importance of five practices: including the writer or writers in all planning activities, having them become familiar with the available programs, infrastructure and resources, setting limits on what is included, communicating problems as they arise, and scheduling adequate time for revisions and quality control review. Careful planning, anticipation of possible issues, prioritisation and proactive communication with team members are essential for the successful completion of a biologics licence application or new drug application submission.
The experience a submission lead needs
Teams benefit from a submission lead with extensive marketing application experience, because such a lead is better able to mitigate the challenges and risks that arise. Experience is the single most important skill a submission lead needs. Submission leads gain it by having had a key functional role in prior submissions, and most importantly by listening to and learning from all of the submission team's discussions, not only those relevant to their own function. In one practitioner view, the experience most needed is to have been through the submission process before, including postsubmission regulatory defence through to approval, because that person knows what the end looks like, what done looks like, and even what done well looks like. This knowledge enables the lead to give the guidance and direction a team needs as new issues arise, timelines shift and the team struggles with critical periods of activity. Experience also enables the lead to guide the team strategically to a solid and detailed strategy, content plan and timeline long before the actual submission work starts. The submission lead has ideally faced these situations before, lived through various scenarios and solutions, and come out with a good sense of what works, what does not, and how to plan for and mitigate the inevitable pitfalls. Such a lead is in a position to keep the team focused and drive it to success, which the lead does by being focused, thinking in terms of scenarios, and ensuring the team is clear on its roles, responsibilities, actions and agreed decisions.