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PRE-SUB 510(K)*– Yes or No?

Don’t file a Pre-Sub for a 510(k) when you don’t need one. A Pre-Sub for a 510(k) should not be seen as a way to avoid doing your own homework. A Pre-Sub is not without risk and can be time consuming. The potential benefits of receiving feedback to your plans should clearly offset the risk of getting answers you don’t want. There are easier ways to confirm you are on the right regulatory path. If you can confirm a straightforward, reasonably recent predicate cleared by the FDA for the same indication for use and intended use; and there are no major differences in technology, you probably don’t need to submit a Pre-Sub. Know the classification and prior filings for a device most similar to your own and do the spade work to find how FDA would regulate your product. Paladin Medical, Inc. can provide a regulatory assessment and identify any device-specific guidance documents.

Avoid unnecessary anxiety

Only after you have begun to lay the regulatory foundation should you begin to consider whether or not a Pre-Sub could be of value. Starting with a quick analysis of similarities and differences can identify whether or not your new device has a difference that could affect an Substantial Equivalence decision (SE.) If your new product could introduce a new risk to patients compared to current products due to new technology/materials; could be used by a different patient population; or adapt an existing product for a new use, your product might not be a candidate for a 510(k) application. On the other hand, if none of these issues are identified during the regulatory planning, then the time and resources that go into a Pre-Sub may not be worthwhile.

Delaying a decision to submit a Pre-Sub could unnecessarily slow up the preparation process for your submission. Once submitted it can consume more than 60 days to obtain feedback., so if the Pre-Sub is not submitted early in the planning stage the wait for feedback could well overrun your project timetable. You certainly don’t want to ask FDA for input and then jump the gun and plunge ahead before you can receive their answers. Since most development teams don’t easily build a 60-day lag time into their schedule, understanding the pros and cons of a Pre-Sub must come early. Yet, if too early, it is possible that the team may not even appreciate there are uncertainties.

There is always a risk that you won’t like the answers you get back from the questions you ask FDA. An ill developed Pre-Sub can engender less than ideal answers from FDA. We can’t guarantee that a Pre-Sub won’t open Pandora’s Box, but we certainly can reduce that opportunity to a minimum by carefully identifying the type of questions that need answers. The Pre-Sub is not a free for all and respecting FDA’s perspective on a new product is critical to crafting the right questions.

The tradeoffs are thus: if you were to file a 510(k) without prior feedback from FDA you could miss-state the substantial equivalence argument or fail to mitigate certain risks through testing, and unintentionally blunder into a deNOVO application, or even PMA.

Squelch uncertainty

Uncertainty is Kryptonite to investors. If the team cannot confidently adopt a regulatory strategy and have confidence in the 510(k) application pathway, outside funding support can be scarce. The most important reason to file a Pre-Sub is when you can’t afford to be wrong. The biggest risk to a manufacturer anticipating a 510(k) clearance is finding out after the filing that the submission must be “deNOVO” or Premarket Approval (PMA).

Even though FDA has hundreds of guidance documents to help in the preparation of a 510(k), both general and product specific: it is still possible a new medical device has a twist not anticipated by guidance documents and standards. Defining similarities and differences of the new product to predicate products will often help to focus the teams’ understanding of how new features and technologies could introduce new risks not common to the predicate products. Sometimes this effort even reveals risks not identified in an FMEA exercise. As the team starts to appreciate these differences, questions will evolve about the FDA regulatory pathway.

Avoiding the cost of repeating expensive and time-consuming testing is another motivation. The bulk of time and money can be spent on any one or more of 1) biocompatibility testing, 2) preclinical assessments, 3) standards certification (such as to IEC standards) 4) validation trials such as usability studies, and of course, 5) clinical studies. When a company is facing these commitments, it can be important to confirm with FDA that the testing is necessary and that the proposed studies are able to demonstrate SE. The Pre-Sub process will not “determine” SE but when the Pre-Sub presentation includes basic information with well-balanced questions for FDA, the sponsor should know from FDA if the plans have met nominal requirements. At times, a specific topic can trigger a separate Pre-Sub meeting to focus on an issue, but this is typically at the sponsor’s option.

In previous years, making “First contact” with FDA has been another reason that company management has sought a Pre-Sub meeting. Although originally an opportunity for a face-to-face visit, thanks to the Covid-19 pandemic, nearly all Q-sub meetings are via video conference for the foreseeable future. Although manufacturers have lost that person-to-person contact of a face-to-face meeting, the irony is that current WEBEX meetings have the benefit of less cost from travel.

The benefit of a Pre-Sub comes from receiving confirmation of your plans and understanding the Agency’s viewpoint on the information you provided. When properly produced, a Pre-Sub can provide an opportunity for FDA to advise you if your path to 510(k) is sound and provide certain details you may want to add to your 510(k) application.

Drafting the Pre-Sub builds cohesiveness

Composition can concentrate the cadre. Advanced regulatory planning and strategy should be included in the Design Control and Review planning as early as possible. Agreement on product performance sounds simple, but it is amazing how many times team members don’t agree on how a new device will compare with existing alternative therapies and devices. Using the Pre-Sub template can help to focus on information necessary to support the regulatory strategy. Developing a uniform presentation of the product information can help to highlight the potential unknowns. The process of writing the draft becomes a consensus building tool. Making a presentation to the FDA is a great way to consolidate opinions about the new product among team members.

Sometimes the development team is not aware that the indication for use, a different or new technology (including a material) or other features can push the product outside the anticipated product classification. Once the differences of the new product compared to the existing predicates are identified the team can factor in new potential risks due to the new product differences. These new potential risks become key to appreciating if there are mitigations (including test methods and assessments) that are well recognized- or not. Studying prior 510(k)s, guidance documents and standards is an excellent way to see if the team has a handle on how to qualify the new product but may also reveal where there may need to be modifications. This may reveal a need to discuss alternative verification methods with FDA in advance. Tackling this early as part of the design control and review planning helps eliminate uncertainties and drafting a PRE-SUB (even if never submitted) can help to prioritize the team’s objectives.


If your team is uncertain of the device regulatory pathway, uncertain of the best predicate or the impact of a technology or different indication for use, contact Paladin Medical, Inc. We can provide guidance and templates to aid you in drafting a pre-510(k) Pre-Sub, help define the questions for FDA and help you determine if the Pre-Sub is a necessary step. We can produce and submit your Pre-Sub, if that is the right action to take. Our experience and advanced planning skills can help you avoid agony and remorse.

*The Pre-Submission Guidance, originally published February 18, 2014, implemented the broader Q-Submission (Q-Sub) Program, which includes Pre-Submissions (Pre-Subs), as well as additional opportunities to engage with FDA. This article puts the spotlight on the Pre-Sub prior to a 510(k) application, but there are many other opportunities and reasons to obtain FDA feedback. In January 2021 FDA re-issued their Q-Submission guidance but not much had really changed from the previous addition.

Paladin Medical University of Kentucky Department of Biomedical Engineering Paladin Medical Society for Biomaterials Paladin Medical Regulatory Affairs Certification Paladin Medical American Institute for medical and Biological Engineering