November 23, 2022

Handling Rejection – What to Do If the FDA Doesn’t Accept Your 510k Application

My 510(k) application was rejected by the FDA, but I don’t understand why?

So, your 510(k) was not accepted by the FDA. There are many possible reasons for this, but don’t stress. We’re here to help you understand why your 510(k) was not accepted and how to move forward.

The FDA has a “Refuse to Accept” checklist that is used to measure your 510(k) application for whether it has substantial information for an substantive review. The RTA serves to “reward complete submissions” and to “reduce the number of review cycles and total time” for a final decision on your application [1]. All in all, the RTA serves to understand the overall individual components of your 510(k) submission; it is not an evaluation of its adequacy or rationale.

The RTA process begins with the receipt of your 510(k) submission. Once received, the application will be checked for a valid user fee/eCopy, if you do not have one then your submission will be placed on hold until one is received. If you do have one, the RTA review will commence. A decision on your submission will be made in up to 15 days of the initiation of the RTA Review. If it is deemed that your application is administratively complete, then your submission is accepted for a substantive review. If it is deemed that your submission is missing administrative information, your submission is put on hold, and you will be contacted for the missing information. If on the 15th day of review, your submission does not have a decision on its administrative completeness, it will automatically be accepted for a substantive review. For more information on the RTA process, check out the checklist utilized here [2].  

How do you pass the FDA Refusal to Accept (RTA) Screening Process?

So, what level of detail do you need to meet to pass the RTA screening process? Firstly, on an administrative level, your submission must include the following:

  1. Statement of no prior submission for subject medical device.
  2. Reference towards prior submission by file number along with information detailing where in your submission previously given feedback is addressed.

Next, a device description should be given which details the device’s applications, images of all components and modifications to it. Additionally, engineering drawings should be attached if applicable and a complete list of components for the device and previously cleared device.

Following this, a predicate device with substantial equivalence should be identified, compared for indications for use and features. This is vital to your application as it shows that a device that is comparatively equivalent to your submission has already been approved by the FDA for the same features and intentions of use.

Additionally, labeling for your submission should be included that includes outer package labeling, the instructions for use (IFU), and a surgical technique manual. The indications for use should be consistent across the form, IFU label, and 510(k) summary.

Next, your submission should be classified as either sterile or non-sterile. So, what constitutes a sterile medical device? To be considered a sterile device, your submission should meet one or more of the following criteria:

  1. Sterilization method including dose for radiation
  2. Description of method to validate the sterilization parameters
  3. Sterility Assurance Level
  4. Description of packaging
  5. Shelf-Life/ Expiration date
  6. Methods that will establish packaging and device performance is maintained for entire shelf-life

If your device is not sterile based on the criteria previously listed, it should be non-sterile and match the following criteria:

  1. Cleaning/Disinfection Method
  2. Sterilization parameters
  3. Shelf-life is not applicable
  4. Statement for why the performance data is not needed to maintain device performance

Per ISO 10993-1, medical devices should be assessed for their biocompatibility in their evaluation of risk. Therefore, the FDA requires that materials and standards be specified in your application. Additionally, should biocompatibility not be tested and presented with your submission, rationale for why this was not needed should be provided. Any changes to your submission’s biocompatibility should also be stated. For more guidance on the determination of whether your device should be tested for biocompatibility, check the guidance document provided here [3].

Finally, another key aspect to your submission is performance data. This includes a test report summary detailing the test performed, the methodologies, results, discussion, and conclusions from the testing. Additionally, rationale for the potential worst-case components/constructs should be included. Additional to this, a complete test report should be submitted with your submission. This includes the test performed, worst-case construct, methods, result tables, images both the testing set up and failure modes, the corresponding loading curve graphs and detailed discussion and conclusion on the testing findings presented.

What if your submission does not have specific subject systems to detail information on?

Not a problem, the FDA understands medical devices differ across a broad spectrum of uses and knows each submission will be unique and different. If you have no information to provide on a specific subject system (i.e. software), just note “Does not apply” in your submission to inform the FDA reviewer that you did see the section was required in your application, but that your submission is not applicable.

As this process can be lengthy and confusing at times, it is recommended that your first 510(k) submission be done with a qualified and experienced regulatory affairs representative. Having an RA work with you will ensure all sections of your submission are completed properly and in accordance with the FDA checklist previously discussed. Once submitted, you can always reach out to an FDA representative at 510K_Program@fda.hhs.gov for status updates on your submission. 

References:

[1] Brittany Ferrell, “510(k) Refuse to Accept Checklist: Why is my submission not good enough?” Lead Reviewer, Extra columnar Spinal Devices Team, FDA U.S. Food & Drug Administration

[2] Acceptance Checklist for 510(k), FDA U.S. Food & Drug Administration

[3] Center for Devices and Radiological Health, “Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process,” Guidance for Industry and Food and Drug Administration Staff