- It’s never too early to start planning for your NDA
- Begin assembling your NDA early
- Understand the relevant statutes and regulatory guidelines that apply to your program
- Use standardized templates that are governed by a common style guide
- Enter your study data into your database as you go
- Request a Pre-NDA meeting, ask great questions, and prepare a robust briefing document
- Establish realistic timelines and responsible parties for every aspect of your NDA
- Allow for at least one month for publishing your submission once all sections are final
- Consider the big picture of what it takes to ensure a successful submission
1. It’s never too early to start planning for your NDA
From the time you begin preparing for your Pre-IND meeting and IND submission, and well before you’ve dosed a single patient, you should start thinking about your eventual NDA. For example:
- What is the most appropriate regulatory pathway (e.g., 505(b)(1), 505(b)(2))?
- What clinical studies are needed to support the NDA and product label?
- Are you planning to pursue expedited development and/or expedited review?
- What manufacturing data (e.g., validations, stability) are needed for the NDA?
- Do you need long-term toxicology/carcinogenicity studies to support your application?
- What can you do in-house and what needs to be outsourced?
All these questions (and many more) should be front and center in your mind as early as possible. Even if your NDA submission seems far off in the distant future, early planning can make the difference between smooth sailing and rough seas.
2. Begin assembling your NDA early
All too often, sponsors wait until late in development to begin compiling their NDA, which can put unnecessary strain on resources and timelines. Remember, every piece of the NDA that you can complete and “put on the shelf” is one less piece that you have to worry about later. By understanding exactly what components can be completed early and then proactively completing those tasks, you can breathe a little easier as the submission date approaches.
In most cases, a large proportion of the nonclinical program will be completed by the time the drug enters the clinic. This means that the vast majority of nonclinical studies will already be summarized in Section 2.6 of the IND (with study reports in Module 4). All of this material can be pulled directly into the corresponding modules of the NDA and added to as other studies become final.
On the clinical side, you should begin analyzing your data and writing your clinical study reports (CSRs) as soon as you can. You can even start on the report shell before the study is complete. Then, once final data are available and analyses have been conducted, you can gather the rest of the components together, collect all of the necessary approval signatures, and tuck it all safely away into Module 5 of the NDA. Performing these activities early will also promote efficiency when the time comes to populate the NDA clinical summary sections.
3. Understand the relevant statutes and regulatory guidelines that apply to your program
It is important to understand the relevant statutes and regulatory guidelines that apply to your particular program, to the FDA review division that will be handling your application, and to NDAs in general. While statutes are legally binding, guidance documents are not. However, guidance documents do provide the current thinking of the regulators who will be reviewing (and hopefully approving) your NDA. Deviating from these guidelines should therefore be done with caution, with justification, and in consultation with the appropriate review division at the FDA.
4. Use standardized templates that are governed by a common style guide
When you start to write your IND (and again when you write your NDA), make sure you use standardized templates and that all authoring is governed by a common style guide. You don’t have to have a fancy eCTD template package to put together a masterful submission, but you should ensure that your submission documents adhere to a common format and style whenever possible.
All authors who will be working on the submission should follow the same grammatical, punctuation, numbering, abbreviation, and document conventions and should understand how to maintain the integrity of the underlying document formatting and styles. This may seem like a minor detail in the face of all of the data and scientific weight in the submission, but a polished, well-written, consistently formatted application package that is compliant with current regulatory document specifications goes a long way toward the success of a submission.
5. Enter your study data into your database as you go
Don’t wait until Phase 3 to get all of your early phase data entered, queried, cleaned, and locked. Getting an early jump on data management will save lots of headaches later on and will free up resources to work on other tasks as the NDA submission date approaches. Once the data are locked, you can start generating study-specific tables, listings, and figures to support study reports and summaries within the NDA.
6. Request a Pre-NDA meeting, ask great questions, and prepare a robust briefing document
The Pre-NDA meeting (Pre-BLA if your product is a biologic) is your primary late-stage opportunity to get input from the FDA on your submission. As such, you need to put a lot of thought into the discussion topics you want to raise and make sure that the questions you ask are clear, well-supported, and positioned to allow for substantive comment from the FDA. If there are any unique aspects of your program or submission that could impact successful filing or review and that have not been resolved during prior interactions, then now is the time to discuss them with the FDA. Prepare your arguments and your “Plan B’s” well in advance and understand the potential implications of each of these on your submission quality and timelines.
7. Establish realistic timelines and responsible parties for every aspect of your NDA
Communicate timelines and responsibilities to all relevant stakeholders and contributors, and follow-up often. Timelines should take into account the vast amount of information that needs to be collected, analyzed, interpreted, and communicated within the NDA. One of the best ways to do this is to establish an NDA “tracker.” Whether the tracker is part of a sophisticated software package specifically designed for regulatory submissions, a Gannt chart in a project management software product, or even a simple spreadsheet, the most important thing is that it must contain certain key and actionable information about the submission. This includes a listing of constituent documents with appropriate granularity, responsible parties (e.g., primary author and reviewer), current status of each document, and due dates. Additional information may be added, if desired, but remember – this is a living document that should be easy to comprehend, updatable in real time, and accessible to everyone involved in preparing the submission.
8. Allow at least one month for publishing your submission once all sections are final
Publishing timelines are often treated as something that can be compressed at will if “more critical” tasks like authoring or scientific review take longer than expected. While publishing timelines can sometimes be shortened, especially if study reports and various sections of the NDA are being finalized as you go, it is crucial not to underestimate the vast amount of effort and time involved in setting up a proper submission. Even with leading edge software, publishing requires a significant amount of time to ensure compliant document formatting, hyperlinking, bookmarking, and arrangement within the eCTD framework, not to mention quality control activities and final validation of the submission. Compressing publishing timelines should be done with caution, prospectively whenever possible, and always in direct consultation with the publishing team.
9. Consider the big picture of what it takes to ensure a successful submission
Whether this is your first NDA or only one of many that you’ve done, take a moment to consider the big picture of what it takes to ensure a successful submission. Pulling together an NDA is a vast undertaking that requires an enormous investment of time and effort to complete. Consider the capabilities and expertise at your company or institution, as well as the internal capacity that you have to accomplish the requisite tasks in your desired timelines, and then make a realistic assessment of whether additional support is needed. In any case, don’t be afraid to seek out experts who can support the success of your submission.
Nuventra offers a number of scalable services to help our clients produce high-quality, compliant NDA submissions. Whether you are thinking of outsourcing your entire NDA, need a partner to help with publishing and submission, or even if you have only one or two documents that could benefit from review by an experienced clinical pharmacology expert – whatever your need, Nuventra can help.
Our veteran senior consultants, former FDA reviewers, and experienced supporting staff of medical writers, project managers, programmers, publishers, and more, have the experience and expertise to support all of your NDA preparation needs.