Rescuing an FDA submission may be necessary at any of the first four steps of the process: discovery/concept, preclinical research, clinical research, and FDA review. Regardless of where you are in the process, there are steps you can take to ensure your submission has the best chance of approval.
If you haven’t begun your FDA submission yet, congratulations! When it comes to the FDA, the best approach is a good offense, so use all of this information to be as prepared and thorough in your application as possible.
Rescue Your FDA Submission: Get Set Up Right with your IND
Even before clinical trials begin, there are steps you can take that will make your future FDA submission more successful. When you’re ready to submit your Investigational New Drug (IND) application (see FDA application procedures here) to receive permission to start clinical trials, use these expert-recommended strategies put together by BioPharma Dive:
- Use an expression system that has already received regulatory approval and a host cell line with a well-documented heritage
- If you will need to outsource development and manufacturing (very common with small biotech companies), stick to one company that provides both and has a good track record
- Plan for future manufacturing capacity now with capability (or a partner’s capability) to handle global manufacturing and all the life cycle needs of your product
Once your IND is approved by the FDA, the clinical trial journey should look like this:
Rescue Your FDA Submission: Check Your NDA Submission
So, you’ve worked like crazy to develop a new drug, and have probably spent more time than you planned working through clinical trials. But the FDA submission isn’t quite a reality yet. An NDA (New Drug Application) is the next step. For those of you who have already successfully been through this process, feel free to gloss over this section, but please add in any advice and tips in the comments.
Nuventra has a great blog on Preparing for a Successful NDA, and their first point is the approach we recommend for the entire FDA approval process: Plan early and thoroughly. Know which regulatory pathway is best, know which clinical studies you need, decide if expedited development is appropriate, know what manufacturing data you need, know what studies you’ll need to support your NDA application, and determine what can be done in-house and what needs outsourcing.
Everything you plan in advance for (and document thoroughly) will help smooth the process going forward. The best resource for knowing what you’ll need for your NDA is the FDA’s website on New Drug Application. Nuventra recommends using the standardized templates and a common style guide, and ensure that everyone contributing to the submission uses exactly the same writing and referencing formats—it will contribute to the success of your application.
You can also request a pre-NDA meeting with the FDA, which is highly recommended. Prepare for it as if you’re preparing for a high-level interview. Have all your information and questions ready in advance.
An NDA takes significant time to prepare. Communicate clearly with everyone involved, and make sure to give at least a month for publishing once everything’s ready. Although it’s the FDA’s goal to respond to 90% of NDAs within 10 months of application, it doesn’t always happen, so a perfect NDA is your best chance at avoiding unnecessary delays. If you’re running into challenges, get expert help before submitting.
Rescue Your FDA Submission: RTA for 510 (k) Submissions
If you’re submitting an application for a medium-risk medical device or IVD, there’s an intermediate process by the FDA called a Refusal To Accept (RTA). As Jon Speer shares in his Tips to Help Your 510(k) Submission article, it’s not uncommon to receive an RTA. This can be a good thing! The RTA is not a refusal of the contents of your application, but rather a quick review of your submission for anything missing from the application checklist. You can read the FDA summary of an RTA here.
Since the review must provide a response to your FDA 510(k) submission within 15 days of your application, this mechanism provides near immediate feedback that you can address. If you receive an RTA, it’s very beneficial to connect with your reviewer to discuss your application and correct any errors or missing information.
Here’s what Speer recommends to increase the chance of avoiding an RTA:
- Use the FDA RTA checklist (Greenlight has a step-by-step guide)
- Provide protocols, results, and reports for sterilization validation, biocompatibility, and electrical safety testing
- Match your predicate as closely as possible with tests, data, and performance results
- Take a team approach to FDA questions, prepare your answers, and then talk directly with your reviewer
While the official FDA review time for your 510(k) submission is 90 days, the clock stops if an RTA is issued, or an Additional Information (AI) letter is sent. If either of these occur, you have 180 calendar days to respond.
After receiving 510(k) approval, you need to list your product with the FDA, register your company (for first-time approvals), and pay the annual establishment registration fee.
Rescue Your FDA Submission: Every Detail Matters
This is a place where perfection is the goal. As I’ve already mentioned, even things like consistent formatting, fonts, and referencing are necessary for a successful FDA submission. If you’ve been rejected or if you want better odds of succeeding on your first application, Treximo offers some great advice in their blog on Tips to Get FDA Approval.
The first (and easiest) tip is to make sure there are no mistakes in your documentation. Provide a clinical research reference to every claim in your submission. Do not state anything without the research to back it up. Include the records from every stage of development. This is a bit of a ‘go back in time’ requirement, so hopefully your research methods have included detailed records through each stage.
Even though you may have the research to support your claims, it needs to be presented in the right way. Treximo recommends using statistical experts to “ensure an appropriately sized test group is selected and research data is collected, analyzed, and presented in a relevant and accurate format.” Engaging a statistical expert is also a valuable strategy for rescuing a failed FDA submission.
Once you have this data, how you unfold the story of the data is important. Is it digestible and easy to read and understand?
If you’ve followed our IND tips, you’ll already be set up with manufacturing best practices. The Treximo article notes that the FDA routinely inspects these facilities during the approval process.
The last tip is to focus on clear and regular communication with sponsors, researchers, and the FDA. “Close communication with the FDA will reduce the need for repeated review cycles and help increase the chances for approval.”
Rescue Your FDA Submission: The Importance of PDUFA
Thirty years ago, slow drug approval was a concern for drug manufacturers, the FDA, and the public. Out of this concern came the first PDUFA law in 1992. In exchange for the FDA to collect fees from drug manufacturers, the FDA and drug manufacturers agreed on time frames for drug approvals.
From an investor’s/trader’s point of view, these timeframes give a good indication of how the drug is moving through the process. They can track the date the NDA is submitted, the date the FDA is expected to respond, and any events throughout the review process that will impact the approval timeframe. A company’s stock will respond to the events along this timeframe.
Rescue Your FDA Submission: A Summary
In general, there are two things that can go wrong during an FDA submission:
- Not communicating with the FDA consistently and transparently leading up to the NDA submission
- Not taking the time to really think about consulting 3rd party partners in areas such as statistical analysis and potential issues before going to the FDA
To address these problems in advance, prepare a proactive plan on how to research the aspects of your drug/device in depth so you provide an all-encompassing FDA submission, and then be proactive while packaging the submission so the focus is on the information, not anything that may distract from this. An FDA rejection can often mean going back to the beginning, and filling in any missing research and information before repackaging it for submission.
We also recommend engaging marketing expertise before submission. When the marketing and science people are talking with each other throughout the process, the relevant messaging can be presented in the clearest way. Always ask each other to whom and for what reason in every aspect of the FDA submission so the review can focus on the right indications for the drug/device.
An FDA submission is an extensive and exhaustive process that must begin long before it’s time to gather everything together. In some ways, you cannot do too much research to prepare for submission, and this detailed and careful preparation will lead to the best chance for approval.