Does the thought of developing a submission for the marketing approval of a new drug fill you with dread? How do you avoid losing all of your holidays and weekends when developing a submission? Or burning out your team? In my career, I’ve helped teams develop robust submissions with minimal disruption to people’s lives and minimal stress. It’s not a fairy tale! It is achievable. But it does require a lot of work, especially upfront. In this blog post, I’ll describe the planning process I use to help teams streamline developing high quality submissions.
Submissions: A love/hate relationship
If you’ve worked on submissions, you’ve probably had at least one bad experience. Personally, I love the opportunity and challenge of consolidating information from such a diverse group of scientific, regulatory, and drug development experts.
Common themes for submission negativity, include:
- “Everything comes in at the last minute.”
- “People always expect the writers and publishers to make up for all the time the rest of the team wasted early in the process.”
- “Why even create a timeline? No one is going to stick to it.”
- “Submissions require you to give up holidays and weekends.”
Many of these issues can be remedied by looking for solutions rather than thinking of them as problems.
The keys to success
There are multiple steps you need to take to have a (relatively) stress-free submission process. First, do your homework. This means asking many questions regarding the project at the onset. Start asking these questions before the kickoff meeting, and certainly before you start getting into the data and deliveries. Ideally that work starts 9 to 18 months before the submission date depending on the size of the program and the scope of the submission. You need to make detailed plans, and I’ll show some examples of that later.
The team needs to meet regularly. In those meetings, document the minutes and actions. This documentation allows you to hold team members accountable for their deliveries. You need to communicate relentlessly. And you need to be the “calm in the storm” because there will be stormy times on the project! If you’re in a lead role, be the person who can help move the team forward despite any chaos.
Every project has a beginning, middle, and end. I refer to these as a “discovery phase”, the “drive phase,” and the “survive phase.” The discovery phase includes the kickoff meeting and planning the document shells. The drive phase is the longest and encompasses developing the team drafts and final drafts. The survive stage comprises the approvals and the actual submission.
The discovery phase: Learn the lay of the land
Many teams miss opportunities to be more successful in the discovery phase. Start by learning about your team and their personalities. Learn not just who they are but also their skill and experience levels. Who is going to be the calm in the storm versus who is going to stir up the storm in the first place?
You also need to learn all of the associated processes. What’s the document review and approval process? Are there templates for the documents and project planning? Obviously, you must know the product, the scope of the program, the type of submission being pursued, and the proposed indication(s).
In addition, learn whether any existing documentation or plans are already in place. Has someone already developed a submission plan that captures existing agreements about timing? If you know when deliverables are expected, you can build on that foundation, rather than starting from scratch.
Moreover, you need to determine the outstanding or rate-limiting documents or data. These key milestones will drive the submission date, which determines how much time you have at each step, especially towards the end.
One frequently overlooked, but critical, factor is the history of the program, especially regulatory interactions. When I’m starting to develop a new submission, I request copies of all of the minutes of the meetings that have been held with the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), or other regulatory bodies. Review these if the team hasn’t already. If your team has this documentation assembled already, that is ideal.
If your project doesn’t have this information, I recommend reviewing those minutes and creating a summary document that captures all agreements with that health authority. Then follow up with the team to ensure that that the agreement was actually followed through and implemented. Every time I’ve been in a position to do this for a submission project, I’ve found something that didn’t get addressed or didn’t get followed through on the way that was agreed, and therefore needed to be highlighted in the summary documents.
In addition, learn the strength and weaknesses of the product and development program. Past interactions with health authorities provide some regulatory perspective on what they thought were strengths or weaknesses. Sometimes gaps or discrepancies develop between what you agreed on with the agency and the current situation. For example, team members, the target patient population, or the standard of care for the drug’s indication could have changed. There may be perfectly good justifications for these changes. The recalibrations that were made to account for these changes in your drug’s development path may not have been communicated to the agency. So, these changes must be accounted for in your documentation and submission.
The discovery phase: Establishing your credibility and regulatory writing processes
Now that you’ve learned as much as possible about the drug program’s team, processes, and regulatory history, you establish your team and everyone’s role on it. In the discovery phase, you learned about previously established processes. This is when you attain agreement on the specifics for this submission. Create a grid of the reviewers and approvers for each document. This grid will help these team members know what’s expected of them for those documents. It’s helpful to agree on the approval process and signatories, so that everyone knows which documents need a signature and which ones just need a verbal or e-mail approval. Moreover, confirm which documents require a formal audit/Quality Assurance (QA) check versus just Quality Control (QC).
Don’t forget to confirm and allot time for that QC and publishing! Often, the regulatory operations and submission publishing aspects are missing from timelines. They shouldn’t be. Take your regulatory operations group into account. Typically, they get squeezed at the end. But if you include them in the process and account for their time, you can avoid that stressful situation.
Make a plan, man
Based on everything that you’ve learned and the processes you’ve established, you’re now ready to develop detailed plans. Identify dates that could affect the timeline: team members’ vacations, key program milestones (final database lock, pre-NDA meeting), and external conflicts like scientific conferences that team members attend. Identify these “blackout” dates early so you can plan around them.
Then, you need to reach full agreement on the detailed plan. The plan should be transparent to the team so that they know the expectations.
Book document reviews and comment resolution meetings in people’s calendars. It decreases the likelihood that they will double book themselves. Also, if meetings are in someone’s calendar, you can send them reminders.
Failing to plan is planning to fail! If you don’t have a timeline, there’s no way you can expect people to follow it. Treat this timeline as something that doesn’t change unless absolutely required.
Take home messages
The key stages in a submission are discovery, drive, and survive. I’ll discuss the latter two stages in an upcoming blog post. To recap, the discovery phase is when you determine the strengths and weaknesses of the program, its history, the process used, and the drug/disease/indication background. Ideally, schedule your kickoff 9 to 18 months before the submission date. The result of the kickoff is detailed plans that you then make transparent to the team. By having a strong plan that is well communicated, you are much more likely to have a smooth submission process that both places your drug in the best light for regulatory bodies and reduces the stress and chaos that so many associate with submissions.
To learn more about best practices for establishing submission timelines that won’t change, minimizing document re-work when submitting to multiple countries, and identifying leadership and project management skills helpful to regulatory writing, please watch a webinar I gave on this topic.