As you are probably aware, a 510(k) submission is required in order to get FDA market clearance for nearly all Class II devices.

With each 510(k) submission I am part of, there are definitely things to learn and to apply to future medical device product development projects and 510(k) submissions.

Here are four things I’ve learned about the FDA 510(k) submission process that you can use to your advantage to ensure a smooth process.

1. A 510(k) Submission Will Take More than Nine Months

Technically speaking, FDA has 90 days to review a 510(k) submission. But if you think you will get clearance from FDA within 90 days of making your submission, chances are you are mistaken.

From a project management perspective, I suggest that you bank on a timeline that exceeds 90 days.

I’ve heard tales of 510(k)s getting clearance in 45 days. I’ve also heard tales of 510(k)s taking longer than a year.

Generally, I advise medical device companies that it will take from 6 to 9 months from the time your 510(k) is submitted until receiving the coveted FDA market clearance letter.

To give you some perspective, the last two 510(k)s I worked on took 10 and 11 months from the date of submission, respectively.

So why were there delays? Why do 510(k)s take longer than 90 days?

Keep in mind that there are several points in time during the 510(k) review process where FDA can kick a submission back to you.

Refuse to Accept

The “refuse to accept” (RTA) review step now in place for FDA 510(k) reviews is an important step to get correct.

RTA is an administrative type of review instituted by FDA a few years ago. The primary purpose of this step is for FDA to confirm that the contents provided in your submission are what is expected and complete. Generally, this RTA step is not a review of the specific details and substance of the 510(k).

If FDA determines there are issues with the contents provide–such as expected information is missing or there are mistakes found, then FDA will notify you that the 510(k) needs corrections before it can be accepted. FDA will provide you an analysis via their RTA checklist, identifying the gaps and issues.

Three common mistakes that will result in FDA refusing your submission include:

1.    Indications for use statement is inconsistent throughout the submission. Make sure every single place where you state indications for use are identical, word for word, verbatim.

2.    Missing/incorrect page numbering. Do make sure every single page of your 510(k) includes a page number. Pages can be numbered from beginning to end of the entire submission. Or you may choose to number each section individually. Regardless of convention chosen, make sure every page is numbered properly.

3.    Missing/issues with table of contents. You do need to provide a table of contents. The table of contents does need to include page numbers too.

(Special Tip: I recommend using the FDA RTA checklist as you finalize the 510(k) preparation process. Complete the RTA checklist as a final check before you submit to FDA. Include the specific citations of where the RTA questions are addressed in your 510(k), including the specific page numbers.)

If you do not pay attention to these details, getting through the RTA step of a 510(k) review can take three months.

Be Prepared for Questions

Every single 510(k) submission I have been a part of has resulted in a round of questions from FDA.

Of course if you could anticipate what FDA’s questions are going to be, you would include this evidence as part of the submission to begin with.

Answering FDA questions can definitely be time consuming. They might require additional, extensive testing. Doing so can easily take several months too.

When you get these questions from FDA, do take time to understand what the reviewer is asking. I advise organizing these and determining an action plan.

It is very possible that you are not entirely clear about each and every question being asked. Reach out to the reviewer and request a conference call to go through each of the questions to be sure you are clear. Do not make assumptions.

Getting some clarity and direction from the reviewer can be important to the tasks required to address the questions.

Yes, I know. There might be times when FDA has asked a question that you may not completely agree with. It definitely happens. If you do not agree with the question, do be prepared with objective evidence to support your justification and rationale. Presenting this to the reviewer during a conference call is the best time. It doesn’t mean the reviewer will always accept your argument, but you should present your case.

2. Content of a 510(k) Submission Must Be Thorough

Historically, a 510(k) submission entailed summaries of testing and resuts. For example, addressign performance testing, it used to be okay to provie testing summaries.

However, this seems to be a thing of the past. In my recent experiences, FDA specifically requested mroe than just the test summaries. FDA requested all test protocols, data, and results.

FDA used to accept “I promise” statements for some testing such as sterilization validation and electrical safety testing. This is no longer the case. Do include sterilization validation as part of your 510(k) submission. Do include electrical safety testing as part of your 510(k) submission.

Also, the 510(k) summary used to be a high-level overview of the performance testing conducting to support substantial equivalence. Most 510(k) summary statements are a couple pages in length. Now, it seems FDA also expects the 510(k) summary to be much more thorough and comprehensive. It’s possible that 510(k) summary statements will be several pages in length.

3. Substantial Equivalence One To One

Of course the premise of a 510(k) submission is to demonstrate that your medical device is substantially equivalent to a device which has already been cleared by FDA.

This is still the case.

Demonstrating substantial equivalence seems to be more involved than it used to be. If the predicate device makes a claim about performance, you need to demonstrate your medical device is at least as equivalent.

The same is true for product labeling. If a predicate device includes information in their product labeling, you will also need to do so. And will need to support all claims with performance testing and objective evidence.

Also, FDA prefers your medical device to align exactly with the predicate. FDA prefers intended use, indications for use, contraindications, product labeling, performance criteria, etc. to be as close to the predicate device as possible.

Do note that it is possible to leverage a “multiple predicate” strategy to demonstrate substantial equivalence. Expect that the more that predicate(s) deviate from your device, the more questions, issues, and concerns that will be raised during FDA review.

4. Consider a Presubmission

Maybe this should be step #1. If you have questions or doubts about your pending 510(k), I encourage you to explore the idea of a presubmission.

The presubmission is a good vehicle to communicate with and ask questions of the FDA prior to making a 510(k) submission. FDA has a guidance document regarding the presubmission program.

The advantages are that a pre-submission is no charge. Expect the process to take 75-90 days after you submit. So this is definitely something to consider early in your process.

For additional guidance, FDA also has a presentation available for review.

Wrapping It Up

To reiterate, the 510(k) submission process and what is expected of device markers has changed substantially over the past few years.

By making sure you consider the four items above, you and your team will have a better idea of what to expect of you going into the process and improve your chance of getting clearance on or before your target release date.

Jon Speer is cofounder and vice president of QA/RA at greenlight.guru. If you’re interesting in learning more specific tips and best practices to improve your 510(k) submission process, you can check out this free webinar on the topic.  

From:MDDI