February 25, 2016 | Tim Garver, PhD, Executive VP and Chief Operating Officer | Medical Writing Services
You’re finally there! You and your colleagues find yourself at the doorstep of being able to submit either a New Drug Application (NDA) or Biologic License Application (BLA) for a compound that your team has been dedicated to for years. The hard work of bringing a new compound to market – and to the patients who need it – is about to pay off. It’s time to begin planning for your submission.
“Submission planning” – what does this encompass exactly? And when and how do you go about doing it?
It’s More Than Just About “Creating Timelines”
The development of a submission plan involves more than just creating detailed timelines, although that’s certainly an important part of it.
Submission plans must be strategic – that is, they need to be both tailored and dynamic. Tailored to fit the anticipated work, resource allocations, and Sponsor work practices (ie, one size does NOT fit all), and dynamic, because things WILL CHANGE along the way that will require periodic “course corrections.”
So, When Do You Start?
As a general rule of thumb, IMPACT encourages submission planning to begin at least 12 to 18 months prior to the desired submission date.
You think that’s too early? Consider everything that still needs to be accomplished.
Finishing up pivotal trials. Completing remaining nonclinical requirements. Polishing off final special population studies. Dealing with manufacturing scale-up and final stability data. That pesky Pre‑NDA meeting. Beginning to think about possible FDA Advisory Committee Meeting vendors and external support. Oh, and then writing up all of your NDA/BLA documents.
Yes, 12 to 18 months out seems about right!
What Goes Into The Submission Plan?
As alluded to above, some people think that a submission plan is synonymous with their “NDA timelines”. But a solid – or better said, strategic – submission plan is composed of more than a well‑thought out Gantt Chart.
At a minimum, a submission plan should include the following:
- By-discipline Risk Assessments
- NDA/BLA Key Messages Document
- Submission Content Plan (ie, the Submission Tracker)
- And, of course…the Submission Timelines
In upcoming posts, we’ll dig deeper into some of these submission management tools. For this post, we’ll provide a high-level review of how these tools are developed and how they’re inter-related, as well as the value each one provides when constructing your overall submission plan.
Assessing Potential Risks to your Submission
|In order to be able to develop a solid submission plan, it’s imperative that everyone has a clear understanding of the risks within their particular discipline.
What kind of risks are we talking about?
There are two main types of risks that can have a potentially negative impact on the submission – risks to the submission date, and risks to the potential approvability of the application (ie, possible “review issues”).
Typically about 12 months prior to the anticipated submission date, we suggest that each discipline (eg, clinical, toxicology, CMC, clinical pharmacology) go through the exercise of conducting a formal risk assessment. In fact, IMPACT recommends going through this exercise as one of the first steps in developing your overall submission plan…many times in advance of constructing the first draft of the timelines.
How is this done and documented? After all risks for a particular discipline are identified, each should be given a probability rating (“What is the realistic likelihood that this risk will occur?”) and an impact rating (“What would be the consequence[s] if this risk was to occur?”) in order to come up with an overall risk value for each potential risk.
The goal here is simple…to build awareness, early on, of problems each discipline could face…and be pro-actively thinking about potential action plans for those risks that fall into the “moderate” to “high” category. However, this is not a one-and-done exercise! Each discipline must reassess their risks along the way – some potential risks will drop off the list while new ones will reappear – that’s normal.
Your Key Messages – The Basis of the Entire Submission
Knowing exactly what messages you want your submission documents to support – and why – is of paramount importance to a successful application. As a result, the second piece of a strategic submission plan is to create a Key Messages Document.
One of the worst positions a Sponsor can find themselves in is wanting to make a labeling claim or, conversely, wanting to build an argument for why something should not be in the label, and realizing that they either don’t have the data or they have not planned for the analyses that are needed to support their position. If this happens late in the game….well, it’s not good!
|As a result, early in the submission planning process IMPACT recommends that, in conjunction with the development of your draft label (notice that we are assuming labeling activities are part of the process), a Key Messages Document is developed. This document should serve as the central location for every important message that needs to be supported somewhere within the application.
However, the Key Messages Document is more than just the central repository for each message point. This is a document that should also identify the main data/results that support the message as well as the location, within the application, where you need to be presenting these data/results in support of the message.
This last part is critical…by documenting where within the application each message should be addressed, you are providing the writers of the submission documents a crucial roadmap that aligns the label with the application itself.
As noted above, the development of the Key Messages Document is an activity that should begin early in the submission planning process…and it should go hand-in-hand with the development of the draft label. And, like the label, the Key Messages Document should receive a broad review at the highest levels within the organization!
Tracking It All: The All-Important Submission Content Plan
A marketing application – what is it, really? Besides being the culmination of years of long hours, lots of victories and the occasional setback, it is a collection of all the documents that a reviewing Agency must have in order to render a decision on the approvability of a compound. Keeping track of it all is no easy feat! Thus, the third critical piece to the overall plan is the “Submission Content Plan” or the “Submission Tracker” as some people call it.
What is it? The Submission Tracker is the tool that identifies, by CTD Module, every document that needs to be included in the application along with corresponding document-specific information such as document metadata, the name of the responsible author(s), expected dates of finalization, anticipated dates regarding the hand-off of final documents to the electronic publishing group, etc.
Generating a detailed Submission Tracker and keeping it up-to-date is vitally important to the submission. Developing the tracker in the first place requires discipline heads to review and confirm each document that needs to be included in the submission.
Keeping the tracker current is important for all submission document contributors….especially for your publishers, because the tracker is the central location of the dates they need in order to plan out their publishing strategy and schedule. The seamless hand-off of submission documents from authors to publishers is incredibly important for a successful submission – it’s so important, we have a prior post devoted to this!!
Finally, the Timelines!
At the very beginning of this post I promised you the development of detailed submission timelines is a big piece of the puzzle. So much so, we are going to devote an upcoming post exclusively to the strategy behind creating aggressive, yet doable, timelines. However, in the meantime, here are some of the key things you should keep in mind when creating your submission timelines:
Do You Need Assistance Managing (Or Writing) An Upcoming Marketing Application?
If the answer is “Yes!” please let us know. IMPACT has extensive experience managing (and writing) marketing applications (NDAs and BLAs) across a wide range of therapeutic fields and for Sponsors of all shapes and sizes. If you or someone you know is in need of our submission management expertise, we’d love to help! Don’t hesitate to contact us, we can’t wait to hear from you.
First 3 images courtesy of Stuart Miles of FreeDigitalPhotos.net. Last image courtesy of cooldesign at FreeDigitalPhotos.net.
Category: Medical Writing Services
Keywords: submission planning, NDA, BLA, marketing application
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