Author name: Robert Packard

There are 38 product classification codes that the FDA selected for the Quik 510k Pilot program to evaluate version 3 of the eSubmitter software.

What are the three (3) advantages of the new Quik 510k pilot program?

There are three (3) advantages of using the eSubmitter software as part of the Quik 510k pilot.  The first advantage of using the eSubmitter software is that the refusal to accept (RTA) process will be eliminated. This change is enormous because nearly 50% of submissions are rejected during the RTA screening process. The hope is that the eSubmitter software will prevent companies from submitting submissions that are missing required content, and therefore the RTA process will not be needed. However, we have seen many submissions placed on hold for technicalities rather than sub-standard submissions. Consequently, it will be fascinating to see the FDA reported outcomes from the Quik 510k pilot.

The second advantage of using the eSubmitter software is that the reviews will be interactive. This means that reviewers are not expected to have any additional information (AI) requests. This also means that submitters will need to respond to questions from reviewers quickly. For example, I have received a call on Friday afternoon after 5:00 pm EDT asking if I could revise to document and email that document to the reviewer by Monday morning. This is an extreme example, but 48-72 hours is typical for a required turn-around during interactive reviews.

The third advantage of using the eSubmitter software is that the FDA is targeting completion of their 510k review within 60 days. This 30-day reduction may seem huge, but the FDA already cut 15 days off its review timeline by eliminating the RTA screening. Second, the FDA picked 38 product classification codes that should not have difficulty reviewing in 60 days. Not all product classifications have the same amount of testing data required, and I do not expect the FDA to be able to review all product classification codes in 60 days–even with eSubmitter.

Although the Quik 510k pilot mentioned that submissions would be zipped, eSubmitter is also designed for electronic submissions through an electronic submissions gateway (ESG). An ESG has the added advantage that you will not need to ship your submission via FedEx. This advantage will gain you only a maximum of 24 hours, but I wish I had those 24 hours last week. Every year, in the last week of September, all the small businesses with small business qualifications try to submit their 510k before the end of the fiscal year (i.e., September 30). This year I had four clients that were in this position. One was unable to get the data they needed to complete their submission before September 30. The other three were making last-minute changes up until the afternoon of Thursday, September 27. One of those submissions was extremely challenging because the submission included video files that exceeded 1GB in total. Therefore, I called CDRH’s eCopy Program Coordinators at 240-402-3717. They were accommodating. They said that it would be best to provide two identical eCopies or to save the MISC FILES and STATISTICAL DATA folders on a separate flash drive. The reason for this is that very large submissions can take days to upload into the CDRH database. Therefore, the picture below shows you what my final solution was for the three submissions this week. The De Novo submission had to be split.

What our firm has done to take advantage of the Quik 510k pilot

If you have a product with any of the 38 product classification codes listed above, and you need to submit a 510k in the next six months, you are very fortunate. The FDA will prioritize your submission, and you are likely to be able to get your device cleared in 60 days or less. Our firm is very anxious to take part in this pilot because the FDA intends to require the eSubmitter software for all submissions in the future, and we expect other product classification codes to be added to the pilot over time. We process dozens of 510k submissions each year, and mastering the nuances of the software is critical to our continued success. I already downloaded the software and installed it onto my computer. I also created a complete submission as a test. eSubmitter saved several hours in the preparation of a 510(k) from the typical 40 hours the process takes. Therefore, I expect the implementation of new eSubmitter software to a triple win for the FDA, clients, and our firm. I plan to request that the FDA add De Novo submissions next to this pilot. The reason is that De Novo submissions typically have more content, and the content is more variable. I think this would be an extremely challenging test for eSubmitter, and the relatively small volume of De Novo submissions would limit the impact upon FDA resources.

Changes to eCopy Requirements in 2018

In 2017, the FDA indicated that eSubmitter software was going to be revised, and it would be approximately two years before companies would be able to submit a 510k electronically to the FDA. Until then, companies must ship an electronic eCopy and a paper copy to the FDA Document Control Center (DCC). The eCopy guidance states, “An eCopy is accompanied by a paper copy of the signed cover letter and the complete paper submission.” However, the FDA’s eCopy guidance has not been updated since December 3, 2015. There are some unofficial changes to the policy, and the FDA no longer requires the complete paper submission. Instead, you can submit an eCopy accompanied by a paper copy of the signed cover letter.

Before February 2018, we would print 1,000+ pages for each 510k submission, pack two 3” three-ring binders in 12”x12”x6” ULine boxes and ship the box to the FDA overnight via FedEx. We typically would charge $400 for this eCopy service. After the unofficial policy change, all of our 510k submissions consist of a paper copy of the cover letter and an eCopy on a USB flash drive. We only charge $150 for the FDA eCopy service, and 100% of our eCopy submissions have been uploaded without problems this year.

What is the difference between creating an eCopy and submitting it with eSubmitter (cited from FDA website)?

There are four differences between eSubmitter and eCopies:

1. An eSubmission package contains PDF attachments and XML file types. The XML files are intended for CDRH IT systems to process the application. Reviewers will not see these XML files. 
2. The parts of the eCopy guidance that describe the structure of a 510(k) submission will not apply to the Quik Review Program Pilot.
3. An eSubmission is organized according to the layout of the template, which places administrative documents (e.g., Form 3674, the 510(k) Summary, the Truthful and Accurate statement) at the end of the submission because their applicability is determined based on the answers to questions in the body of the template (e.g., Form 3674 is only required if the applicant indicates clinical data are included).
4. Electronic signatures are used in the submission (e.g., on the Truthful and Accurate statement), rather than physical signatures.

eSubmitter Template Options

For device 510k submissions, the FDA’s eSubmitter gives you three options:

1. Template Version 1.3, for In Vitro Diagnostic 510k submissions to CDRH only, allows you to create a 510k submission and the eSubmitter software will package your submission in a specially formatted zip folder that you can save to a compact disc (CD), digital video disc (DVD) or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC.
2. Template Version 1.2.1, for Non-In Vitro Diagnostic 510k submissions that are among the 1,000+ other product classifications not included in the Quik 510k pilot (CDRH: Medical Device eCopies), you can create a 510k submission and the eSubmitter software will package your submission in a folder for you. You can then copy the contents of that folder to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC.
3. Template Version 3.2, for Non-In Vitro Diagnostic 510k submissions that are among the 38 product classification codes that are listed above for the Quik 510k pilot program. This allows you to create a 510k submission, and the eSubmitter software will package your submission in a specially formatted zip folder that you can save to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy created by eSubmitter with your paper copy of the cover letter to the FDA DCC. This template is unique to the Quik 510k pilot program. There is a red bar that appears at the top of the screen:

“This template should only be used to construct a submission if you are submitting it as part of the Quick Review Pilot. All others may use the content of this template as a reference to aid in constructing an eCopy. If you are not part of the Quick Review Pilot, do not construct a submission with this template, it will be rejected.”

When you create your eCopy, then you will need to create a volume-based or non-volume based submission in accordance with the eCopy guidance. The volume folders and/or files are saved to a compact disc (CD), digital video disc (DVD), or flash drive. Then you must print a paper copy of your signed cover letter and ship the eCopy you created with your paper copy of the cover letter to the FDA DCC.

Warning: If you are using Windows 10, and you save your eCopy or eSubmitter zip folder on a flash drive, Windows 10 will automatically create a hidden system folder titled “System Information Volume.”  This folder is created as a security feature to enable you to recover accidentally deleted content. However, this folder results in an error when the FDA attempts to upload your submission automatically. Therefore, you must remove this hidden system folder. Instructions for this can be found on our website page about eCopy hidden system files.

This article reviews four of the top reasons for why other companies feel requesting 510k pre-sub meetings is a waste of time, but you can’t afford to.

It only takes my team 8-10 hours to prepare a 510k pre-sub request. The FDA does not charge you a cent for requesting 510k pre-sub meetings, and a pre-sub should be part of every design plan. But most companies are resistant to requesting 510k pre-sub meetings. Here are the top 4 reasons why companies tell me they don’t need to request a meeting:

It’s too late for requesting 510k pre-sub meetings

If you are less than a week away from submitting a 510k, it is too late for requesting 510k pre-sub meetings. The FDA target for scheduling a 510k pre-sub meeting is 60-75 days from the date your request was submitted. That’s 10-11 weeks. Most companies tell me that they plan to submit a 510k within weeks or a couple of months, but most of the companies take several months, and frequently there is a delay that requires six months or more. For example, what if your device fails EMC testing, and you have to change the design and retest for both EMC and electrical safety? At best, you will have an 8-week delay. If you submit a request next week, and everything goes as you plan, you can always withdraw your request for the pre-sub. If you encounter a delay for any reason, suddenly, it’s not too late.

Our design is not finalized yet

I believe that waiting until your design is almost complete is the number one reason why companies wait too long to request 510k pre-sub meetings. If they wait too long, then the previous reason for not requesting a meeting takes over. The ideal time to submit a pre-sub request is 75 days before you approve your design outputs (i.e., design freeze). However, very few people are precise in their design planning and execution. You should try to target sometime after you approve your design inputs, but before you approve your design outputs. As long as you submit an update to your pre-sub request two weeks before the meeting, the FDA will accept it. Also, you can always schedule a date that is later than 75 days if you realize you requested the meeting too early.

We don’t want to be bound by what the FDA says in the 510k pre-sub meeting

510k pre-sub meetings are “non-binding.” That means that the FDA can change their mind, but it also means you don’t have to do everything the FDA says in a 510k pre-sub meeting. If you don’t ask a question about testing requirements, that doesn’t mean that the FDA does not have any testing requirements. The FDA knows what previous companies have submitted for testing better than you do, and they may be in the process of evaluating a draft special controls guidance. If you ask questions, you will have better insights into what the FDA expects. Understanding FDA expectations helps you write better rationales for testing or test avoidance. You also might learn about deadlines for the implementation of new testing requirements that you might be able to avoid. Finally, you can ask the FDA about possible testing options you are considering if the FDA denies your most optimistic testing plans.

There is already a guidance document for our device

Not all device classifications have a guidance document explaining what information should be submitted in a pre-market 510k submission. However, there almost one hundred Class II Special Controls Guidance Documents. Therefore, there is a good chance that the FDA published special controls as part of the regulation for your device or as a guidance document. As part of the special controls, the FDA defines what performance testing is required for your device. If you already know what testing is required, then the value in requesting 510k pre-sub meetings is diminished. But at least three other key benefits remain.

First, you can verify that the predicate you plan to use for comparative testing is not going to be a problem. Although the FDA can’t tell you which predicate to pick, the FDA can tell you if there is a problem with the predicate you have selected. This is especially important if the product is not currently registered and listed, because you may not know if the device was withdrawn from the market after it was cleared.

Second, not all testing standards are prescriptive. Many tests have testing options that require you to make a decision. Input from the FDA may be valuable in making choices between various performance testing options. Sometimes you even forgo testing and provide a rationale instead. FDA feedback on any rationale for not doing testing is critical to prevent delays and requests for additional information later.

Third, there are many different FDA representatives that participate in 510k pre-sub meetings. The lead reviewer will invite specialists and the branch chief to the meeting. Each of these specialists can answer questions during a pre-submission meeting that they are not able to answer during the actual review process. You also have the opportunity to get feedback from the branch chief–who has insight from all the previous devices that were cleared with your product classification. Your lead reviewer is not likely to be as experienced as the branch chief, and may only have been working at the FDA for months. Your request for the 510k pre-sub meeting will help an inexperienced lead reviewer as much as it will help your company.

Learning More about 510k Pre-sub Meetings

On Thursday, February 22, there will be a free webinar offered on the topic of 510k pre-sub meetings. We had 50 people register for the webinar on the first day it was announced, and we have already answered more than a dozen related questions. If you are planning to submit a 510k this year, this webinar will show you exactly how to prepare your request for a 510k pre-sub. You will even receive copies of all of our templates for free.

This article is a copy of my responses to someone that submitted biocompatibility testing questions in preparation for a 510k pre-submission webinar.

Can you please answer the following questions related to biocompatibility for a 510k pre-submission meeting request?

This was the request by a person that registered for a 510k pre-submission webinar that was recorded in February 2018. The person asked some great questions that are very similar to other clients I work with. They also requested the biocompatibility testing questions in a way that did not divulge any confidential information–other than to indicate they live in Germany. Therefore, I am sharing my email response with you. Please register for this webinar and submit your questions. Questions are entered in an open text box, and you have room to ask multiple questions.

Biocompatibility testing question #1: Does the FDA now already ask for the AET (Analytical evaluation threshold) for chemical analyses?

Biocompatibility testing question #2: How can I avoid time-consuming genotoxicity studies for FDA?

Question #3: And how can I face FDA with a cytotoxic wound dressing but which passed irritation, sensitization, genotox, and pyrogenicity tests?

Biocompatibility testing question #4: Which genotoxicity tests are state of the art for the FDA?