510(k) Archives

Archive for 510(k)

eSTAR draft guidance is here, and wicked eSubmitter is dead.

Posted by Rob Packard on October 20, 2021

I hated the the FDA eSubmitter template which was discontinued May 30, 2021. Finally we have eSTAR draft guidance for the new eSTAR template.

History of 510k electronic submissions

The FDA has experimented with a multitude of pilot 510k submission programs over the years to streamline and improve the 510k submission content, formatting, and to facilitate a faster review process. The Turbo 510k program was one of the first successful pilot programs. In 2012 I wrote one of my first blogs about how to improve the 510k process. In September 2018, the FDA launched the “Quality in 510k Review Program Pilot” for certain devices using the eSubmitter electronic submission template. The goal of the this pilot program was to enable electronic submissions instead of requiring manufacturers to deliver USB flash drives to the FDA Document Control Center (DCC). I hated the eSubmitter template, and the FDA finally discontinued availability of the eSubmitter template on May 30, 2021. During the past 15 years, the FDA gradually streamlined the eCopy process too. Originally we had to submit one complete hardcopy, averaging 1,200 pages per submission, and one CD containing an electronic “eCopy.” Today, the current process involves a single USB flash drive and a 2-page printed cover letter, but today’s eCopy must still be shipped by mail or courier to the DCC.

eSTAR Pilot Program is Launched

During the 15-year evolution of the FDA eCopy, CDRH was trying to develop a reliable process for electronic submissions of a 510k. CBER, the biologics division of the FDA, has already eliminated the submission of eCopy submissions and now 100% of biologics submissions must be submitted through an electronic submissions gateway (ESG). In February 2020, CDRH launched a new and improved 510k template through the electronic Submission Template And Resource (eSTAR) Pilot Program. The eSTAR templates include benefits of the deceased eSubmitter template, but CDRH has incorporated additional benefits:

the templates use Adobe Acrobat Pro instead of a proprietary application requiring training;
support for images and messages with hyperlinks;
support for creation of Supplements and Amendments;
availability for use on mobile devices as a dynamic PDF;
ability to add comments to the PDF; and
the content and logic mirrors checklists used by CDRH reviewers.

Medical Device Academy’s experience with the eSTAR Templates

Every time the FDA has released a new template for electronic submissions we have obtained a copy and tried populating the template with content from one of our 510k submissions. Unfortunately, all of the templates have been slower to populate that the Word document templates that our company uses every day. On May 16 we conducted an internal training for our team on the eSTAR submission templates, and we published that training as a YouTube Video (see embedded video below). Then nine days later the FDA released updates to the eSTAR templates (version 0.7). The new eSTAR templates are available for non-IVD and IVD products (ver 0.7 updated May 27, 2021).

Sharon Morrow submitted our first eSTAR template to the FDA in August and we experienced no delays with the 510k submission during the initial uploading to the CDHR database, there was no RTA screening process, and CDRH did not identify any issues during their technical screening process. Shoron’s first eSTAR submission is now in interactive review, which is a better outcome than 95%+ of our 510k submissions. I have several other eSTAR submissions that are almost ready to submit as well. The other 510k consultants on our team are also working on their first eSTAR submissions.

Finally the CDRH releases an FDA eSTAR draft guidance

On September 29, 2021 the FDA released the new eSTAR draft Guidance for 510k submissions. This is a huge milestone because there have not been any draft guidance documents created for pilot programs. The draft indicates that the comment period will last 60 days (i.e. until November 28, 2021). However, the draft also states that the guidance will not be finalized until a date for requiring electronic submissions (i.e. submission via an ESG) is identified. The draft indicates that this will be no later than September 30, 2022. Once the guidance is finalized, there will be a transition period of at least one year where companies may submit via an ESG or by physical delivery to the FDA DCC.

Are there any new format or content requirements in the FDA eSTAR draft guidance?

There are no new format or content requirements in the eSTAR draft guidance, but the eSTAR template itself has several text boxes that must be filled in with summary information that is not specified in the guidance for format and content of a 510k. The information requested for the text boxes is a brief summary of non-confidential information contained in the attachments of the submission. Therefore, these boxes can information that would normally be in the overview summary documentst that are typically included at the beginning of each section of a 510k. If your overview documents do not already have this information, then you may have some additional work to do in order to complete the eSTAR templates. An example of one of these text boxes is provided below:

Summary of electrical mechanical and thermal testing eSTAR draft guidance is here, and wicked eSubmitter is dead.

Another example of additional content required by the eSTAR templates is references to page numbers. Normally the FDA reviewer has to search the submission for information that is required in their regulatory review checklist. In the new templates the submitter is now asked to enter the page numbers of each attachment where specific information can be found. The following is an example of this type of request for a symbols glossary:

Reference to symbols glossary in labeling eSTAR draft guidance is here, and wicked eSubmitter is dead.

Are there any changes to the review timelines for a 510k in the eSTAR draft guidance?

The eSTAR draft guidance indicates that a technical screening will be completed in 15 calendar days instead of conducting a RTA screening. I believe that the technical screening is less challenging than the RTA screening, but the FDA has not released a draft of the technical screening criteria or a draft checklist. I would imagine that the intent was to streamline the process and reduce the workload of reviewers performing a technical screening, but we only have guesses regarding the substance of the technical review and so far our performance is 100% passing (i.e. 1 of 1). The next step in the 510k review process is a substantive review. Timelines for the substantive review are not even mentioned in the new draft guidance, but the FDA usually has the review clock details in Table 1 (MDUFA III performance goals) and Table 2 (MDUFA IV performance goals) of the FDA guidance specific to “Effect on FDA Review Clock and Goals.” In both tables, the goal is 60 calendar days, and our first eSTAR submission completed the substantive review in 60 days successfully. The 180-day deadline for responding to an additional information (AI) request has not changed in the eSTAR draft guidance, but our first submission is now interactive review. I believe this suggests that companies may have a higher likelihood of having an interactive review with their CDRH lead reviewer instead of being placed upon AI Hold, but we won’t have enough submissions reviewed by the FDA to be sure until the end of Q1 2022.

Register for our new webinar on the FDA eSTAR draft guidance

We hosted a live webinar on Thursday, October 21, 2021 @ Noon EDT. The webinar was approximatley 37 minutes in duration. In this webinar we shared the lessons learned from our initial work with the eSTAR template. Anyone that registers for our webinar will also receive a copy of our table of contents template that we updated for use with the eSTAR templates. Unlike a 510k eCopy, an eSTAR template does not require a table of contents but we still use a table of contents to communicate the status of the 510(k) project with our clients. Finally, we reviewed the eSTAR draft guidance in detail. If you would like to receive our new eSTAR table of content template and an invitation to our live webinar, please complete the registration form below.

About the Author

Robert Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certification. From 2009-2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone 802.258.1881 or email. You can also follow him on Google+, LinkedIn or Twitter.

Tags: 510(k), eSTAR, FDA

Posted in: 510(k), eSTAR

How much does a 510k cost?

Posted by Rob Packard on August 3, 2021

How much does a 510k cost is the most common question I receive from customers, and there are three parts to the cost of a 510k.

There are three parts to the 510k cost of submission:

Testing
Submission Preparation
FDA User Fees

The highest cost is testing

The testing cost is the biggest cost, but I think the average is around $100K for our clients. For devices that only consist of software (i.e. software as a medical device or SaMD), the testing costs are less, but the cost of documenting your software validation and cybersecurity will be more extensive than the cost of preparing your 510k and the FDA user fee. The more you can do in-house, the lower the testing costs will be. Biocompatibility testing for a non-invasive device might be only $13,000, but a long-term implant can cost as much as $100,000 for the implantation studies. Sterilization validation testing depends upon the method of sterilization and whether you are doing a single-lot method or a full validation. Typical costs for EO sterilization validation are around $15,000, and then you should add several thousand more for the shelf-life testing.

For devices that are powered and/or have software, you will need to perform software validation in accordance with IEC 62304 ed 1.1 (2015). There are also five FDA guidance documents that apply:

You can do all of the software validation in-house, but some firms choose to outsource the validation of software. In the long-term, you need to learn this, and it pays to hire an expert in IEC 62304 to help your team learn how to document software validation if you have not done this before. Typically, software validation documentation will be between 300 and 1,000 pages in length.

Electrical safety and EMC testing are often the most expensive part of the testing process for our customers. EMC testing should always be done first to make sure that you can pass the immunity and emissions testing. If you have to modify the device to pass the EMC testing, then you will need to repeat any electrical safety testing. The total cost of this testing is typically $50-60K.

Performance testing is the last part of the testing process. Performance testing should be performed on sterile and aged products if your product requires sterility and you are claiming a shelf-life. Most of the testing is benchtop testing only to demonstrate performance. This includes simulated use testing (e.g. summative usability testing), cadaver testing, and computer modeling. Benchtop performance testing is typically tens of thousands of dollars to complete, but you might be able to do the testing in-house. If animal testing is required, this typically costs around $100K. Finally, if a human clinical study is required (i.e. ~10% of 510k submissions). Then you should expect to spend between $250K and $2.5 million. Some simple clinical studies (e.g. IR thermometers) cost less than $100K, but these resemble benchtop performance testing in many ways.

The second highest cost is the cost of submission preparation

Medical Device Academy has two different options for preparation consulting fees. Your first option is hourly consulting fees. The second option is a flat fee. As of October 2022, we are charging $3,500 for pre-submission preparation and $17,500 for 510(k) submission preparation.

510k cost #3 is the cost of the FDA user fee

You have three options for your FDA user fees:

Third-party review
FDA review (standard user fee)
FDA review (small business user fee)

The first option is to avoid the FDA altogether and submit to a third-party reviewer. We only recommend one third-party reviewer (i.e., Regulatory Technology Services), because the other companies do not have sufficient experience to have predictable review times and positive outcomes. The typical cost for a third-party review by RTS is 6% more than the FDA Standard fee (i.e., ~$21,000).

The second option is to submit directly to the FDA. The standard user fee for FDA review of a 510k is $19,870 for FY 2023.

The third option is to apply for small business status. For companies that have annual revenues of less than $100 million USD, the FDA will grant you small business status. For companies with small business qualifications, the FDA user fee is reduced to $4,967.

FY 2023 User Fees 1024x587 How much does a 510k cost?

Reduce 510k cost by applying for small business status

Any medical device company with revenues of less than $100 million annually can apply, but you must apply each year. There is no application fee, but you must complete FDA Form 3602 if you are a US firm. The form must be completed for each subsidiary too. FDA Form 3602A must be completed for foreign firms, and the national tax authority must verify the accuracy of your income statement on the form to submit it to the FDA. If your national tax authority refuses to sign the form, you can justify it, but I don’t know anyone that has successfully done this yet. The qualification review by the FDA requires 60 days. Therefore, you should apply every year in August for the next fiscal year (October 1, 2021 – September 30, 2022, is FY 2022). The form will request that you include your Organization ID #. A Dun & Bradstreet Number (DUNS #) is also required if your firm is located outside the USA. Finally, you need to attach a copy of your tax return. Therefore, you must file your tax return–even if your firm had a loss or had no revenues. You can also take advantage of R&D tax credits in the USA or Canada if you are a start-up device company developing a new device.

About the Author

Rob Packard is a regulatory consultant with 25+ years of experience in the medical device, pharmaceutical, and biotechnology industries. He is a graduate of UConn in Chemical Engineering. Robert was a senior manager at several medical device companies—including the President/CEO of a laparoscopic imaging company. His Quality Management System expertise covers all aspects of developing, training, implementing, and maintaining ISO 13485 and ISO 14971 certifications. From 2009 to 2012, he was a lead auditor and instructor for one of the largest Notified Bodies. Robert’s specialty is regulatory submissions for high-risk medical devices, such as implants and drug/device combination products for CE marking applications, Canadian medical device applications, and 510(k) submissions. The most favorite part of his job is training others. He can be reached via phone at 802.258.1881 or by email. You can also follow him on Google+, LinkedIn, or Twitter.

Posted in: 510(k)

Leave a Comment (0) →

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

Posted by Matthew Walker on June 29, 2021

This article helps you understand how to pass the FDA Refusal to Accept (RTA) screening process 510k submissions – updated Sept 2019 version.

What is an RTA Checklist?

The “RTA” in RTA Checklist stands for Refuse to Accept. The FDA uses this tool to determine if your 510(k) submissions will be accepted or not for a substantive review. Accepted, not approved because this is simply a verification that the required information is included in your submission. As stated in the 2019 FDA guidance document for the FDA’s Refuse to Accept Policy for 510(k)s “a minimum threshold of acceptability and should be accepted for substantive review.”(Ref.1). That does a nice job summarizing the RTA checklist. It is a tool used to help assess whether or not your submission contains the required information to continue with a more thorough review of the contents of the submission itself.

What does the Refusal to Accept (RTA) policy apply to?

The Refusal to Accept (RTA) policy applies to all 510k submissions. The RTA checklist or more checklists apply specifically to each 510(k) submission type:

Traditional 510k
Abbreviated 510k
Special 510k

There is a different RTA checklist for each submission type. The checklists can be found within the Refuse to Accept Policy for 510(k)s guidance document. Specifically, in the PDF document that the FDA reissued on September 13, 2019, the checklists can be found in the following areas:

Traditional 510k – Appendix A. Page 20 (numbered page 21)
Abbreviated 510k – Appendix B. Page 55 (numbered page 56)
Special 510k – Appendix C. Page 91 (numbered page 92 )

Note that in the title of the checklist it is referred to as an ‘acceptance checklist.’ It is not called the RTA checklist until you get to the footer of the page. It is also listed as an acceptance checklist on the FDA website. The best way to think of the process is as preliminary screening by the FDA.

What does the FDA look at during the Refusal to Accept (RTA) screening process?

During the screening process, the assigned RTA screener will review 510k submission and try to identify all of the requirements listed in the applicable RTA checklist. The person screening your submission is required to answer “yes,” “no,” or “n/a” to the questions in the checklist. This person must also enter the document and the page where the information can be found in the submission. Finally, if an element required by the refusal to accept (RTA) checklist cannot be found, then the screener adds a comment at the end of that section in the checklist. The comment will state what your deficiency is and it may even identify a guidance document that can help you address the issue. If you are missing requirements, you will receive an email from the RTA screener with the completed RTA checklist attached. We call this an “RTA Hold” letter. If your submission is not rejected, then your 510k is administratively complete and you will receive an automated email indicating that your submission was accepted and the substantive review will now begin.

Refusal to Accept (RTA) Time Frame

As stated in the guidance document the Refusal to Accept policy includes “an early review against specific acceptance criteria and to inform the submitter within the first 15 calendar days after receipt of the submission if the submission is administratively complete, or if not, to identify the missing element(s).” (Ref. 1). If the assigned screening person is unable to complete the process within 15 calendar days, then you will receive an automated email stating that they were unable to complete the RTA checklist within 15 calendar days and your submission is automatically moved to the substantive review stage of the 510k review process.

Taking the time to perform your own gap analysis before you submit could avoid a simple error. For example, if you forget to include the signed Truthful and Accuracy Statement in your submission it could take 15 days to be notified of that missing element. The person screening your submission could email you to provide this missing element in an interactive review to avoid placing your submission on hold, but they are not required to give you a chance to provide this interactively by email. If you do receive an RTA Hold letter, you might be able to correct missing elements on the same day, but the 510k review clock is automatically reset when your 510k is placed on RTA Hold. There will be another 15-day refusal to accept (RTA) screening of your submission when you respond to an RTA Hold letter.

What to do with the information in the comments of the RTA checklist?

The RTA checklist is the criteria that your submission is being evaluated against. If your submission has deficiencies during the initial review against the RTA Checklist, the FDA will refuse to accept it and the substantive review will not begin until those deficiencies have been corrected. Since the FDA does not hide what they are looking for, or how they will evaluate your submission, use that to your advantage. Assuming that you have correctly determined the type of 510k submission you have, perform a gap analysis of your submission against the RTA checklist. Either perform these actions in-house, or hire an outside consultant to do them for you, but make sure you don’t make the mistake of trying to check your own work because you will miss something.

Scope of the FDA Refusal to Accept Guidance Document

The scope of the FDA guidance document that is provided for the benefit of the FDA personnel that are reviewing your submission and not specifically for the 510k submitter. It is also for the purpose of providing a loose framework for systematically reviewing submissions in a consistent manner. This ensures all submissions receive equal nonbiased treatment. There are some things that this guidance document does not address or alter by its own admission. One of those things is the “substantial equivalence decision-making process once the submission has been accepted for review.” The refusal to accept (RTA) guidance also does not address FDA user fees. Other guidance documents address those issues.

What are the most common reasons for FDA refusal of your 510k submission?

Although there are dozens of reasons (43 to be exact) why the FDA could reject your submission in the 35-page RTA checklist, most of the refusals (~80%) result from a small percentage (~20%) of reasons. The most common is that your submission is poorly organized. Either you did not provide a table of contents, your submission is not organized in accordance with the sections outlined in the guidance, or the pages of your submission are not properly numbered. When you are trying to review a 1,200-page submission, poor organization is extremely irritating and wastes the reviewer’s time. If it were my decision, I would refuse to complete the entire checklist until you gave me a properly organized submission.

The second most common reason for refusal is the submission of a device description that is not adequate. The FDA needs more detail than most companies provide for the device description because they need to understand what the differences are between your device and the predicate device. This includes much more than just the indications for use. Who are the intended patients and users? What is the intended environment of use? What are the materials for patient-contacting components? What is the source of power for your device? Which design features does your device include when compared to the predicate? What is the user interface for your device? Which accessory devices are needed with your device? You can even make the mistake of being inconsistent in your submission by not repeating the content in the device description in other sections of the 510k submission. It is important to duplicate certain content verbatim in other documents such as the 510k summary, the executive summary, the substantial equivalence comparison, and the instructions for use. Paraphrasing and summarizing certain information will not work.

The third most common reason for refusal of your submission is likely to be related to software validation documentation. In addition to complying with the recognized IEC 62304 standard, you also need to comply with the five software guidance documents that the FDA has published. The FDA and 3rd-party reviewers use an 11-item checklist based upon the 2005 FDA guidance document on software validation documentation. In addition, if your device has any of the following 5 elements, your submission must also comply with the two FDA guidance documents on cybersecurity:

Cloud communication
Network connection (active or not)
Wireless communication in any form
USB/serial ports/removable media
Software upgrades (this includes patches)

Finally, biocompatibility is the one testing section of your 510k submission that is most likely to result in refusal to accept by the FDA out of the seven sections requiring testing reports. There are several reasons why biocompatibility results in more refusals than the other six testing sections. First, the FDA requirements go above and beyond the requirements of the ISO 10993-1 standard. Second, the FDA requires that you submit full testing reports for biocompatibility while you can submit summaries for other sections (e.g. sterilization validation). Third, many submitters try to provide a rationale for why testing is not required for their device, but the FDA has very stringent requirements for the use of a biological risk assessment or a biocompatibility certification statement in lieu of testing.

Do you have to follow the RTA checklist exactly?

You can, but you are also not bound by it. Like all guidance documents they “contain nonbinding recommendations”. The checklist is released as part of a guidance document, so it is a guidance and not a regulatory requirement. That being said, if your submission is missing an element in the checklist, your 510k submission will be considered administratively incomplete unless you provide a clear explanation as to why the checklist element is not applicable to your submission or you explain how you meet the 510k submission requirement in another way.

Medical devices vary wildly and there is no one size fits all approach. The FDA recognizes that and includes some wiggle room that gives them some discretion in reviewing submissions. However, 100% of the 3,500+ submissions received each year are screened using the refusal to accept (RTA) checklist and the screening person’s job is to verify that your submission meets the criteria. As it says in the guidance document:

“The purpose of the 510(k) acceptance review is to assess whether a submission is administratively complete, in that it includes all of the information necessary for FDA to conduct a substantive review. Therefore, the submission should not be accepted and should receive an RTA designation if one or more of the items noted as RTA items in the checklist are not present and no explanation is provided for the omission(s). However, during the RTA review, FDA staff has the discretion to determine whether missing checklist items are needed to ensure that the submission is administratively complete to allow the submission to be accepted. FDA staff also has the discretion to request missing checklist items interactively from submitters during the RTA review. Interaction during the RTA review is dependent on the FDA staff’s determination that outstanding issues are appropriate for interactive review and that adequate time is available for the submitter to provide supporting information and for FDA staff to assess responses. If one or more items noted as RTA items on the Acceptance Checklist are not present, FDA staff conducting the acceptance review should obtain management concurrence and notify the designated 510(k), contact person, electronically that the submission has not been accepted. “ (Ref. 1).

The portion above notes that explanations may be provided for omitted portions of the submission. So, the answer to the question is that no, you do not have to follow the RTA checklist exactly. However, if you should purposefully omit a section you should provide an explanation and your rationale justifying why the omission is appropriate for your individual device and 510(k) submission. Again, just because you have included an alternative approach or justification does not automatically mean it will be accepted. The FDA personnel that are conducting the acceptance review will judge whether or not your deviation is acceptable.

What if your 510k submission is refused?

If your submission is refused you will be provided with a copy of the completed RTA checklist and each of the deficiencies you must address will be highlighted. Sometimes there will be an attachment to the checklist that has additional issues that are not in the RTA checklist, but the reviewer thinks you may need to address later. You might also see comments that are not highlighted. These are suggestions from the reviewer that you may or may not choose to address.

There is a 180-day timeline for response to an RTA Hold letter. The response must be submitted to the CDRH Document Control Center (DCC) as an eCopy, and the response must be received within 180 days. If the response is not received within 180 days, your submission will be automatically withdrawn on the 181st day. Your response may not be piecemeal. You must address all of the issues in the RTA checklist or your submission will be placed on RTA Hold again (i.e. RTA2). If you are not sure how to organize your response, a previous blog posting and YouTube video address this topic directly.

About the Author

Matthew Walker – QMS, Risk Management, Usability Testing, Cybersecurity

Matthew came to us with a regulatory background that focused on OSHA and NFPA regulations when he was a Firefighter/EMT. Since we kidnapped him from his other career, he now works in Medical Device Quality Management Systems, Technical/Medical Writing, and is a Lead Auditor. Matthew has updated all of our procedures for He is currently a student in Champlain College’s Cybersecurity and Digital Forensics program, and we are proud to say that he is also a member of both the Golden Keys and Phi Theta Kappa Honor Societies! Matthew participates as a member of our audit team and has a passion for risk management and human factors engineering. Always the mad scientist, Matthew pairs his professional life in regulatory affairs with hobbies in the culinary arts as he also holds a Butchers/Meat Cutters certificate from Vermont Technical College.

Email: Matthew@FDAeCopy.com

Connect on Linkedin: http://www.linkedin.com/in/matthew-walker-214718101/

Posted in: 510(k), FDA

How is your response to an Additional Information Request different from an RTA response?

Posted by Rob Packard on June 22, 2021

A poor RTA response will cause a two-week delay, but an additional information request only gets one chance to avoid the dreaded NSE letter.

An Additional Information Request (i.e. AI Request) is typically received just before the 60th day in a 90-day 510k review, while a Refusal to Accept (RTA) Hold is typically received on the 15th day. If your response to your first RTA Hold (i.e. RTA1) is inadequate, the reviewer will issue another RTA Hold letter (i.e. RTA2) and your 510(k) review clock will be reset to 0 days. You will have another 180-days to respond to RTA2, and issues identified in an RTA Hold are usually easy to address. Most RTA Hold issues also have one or more guidance documents that are available to help you to obtain an RTA Accept letter. You can always request a submission-in-review (SIR) meeting to clarify what information the reviewer needs to address the RTA deficiencies too. If you want to learn more about responding to an RTA Hold, please read last week’s blog. The rest of this article is specific to responding to requests for additional information.

What happens after 60 days during a 510k review?

On the 60th day of the 510k review clock, or a few days prior to the 60th day, the lead reviewer must determine if they need to issue an Additional Information (AI) Request. The alternative to an AI Request is for the lead reviewer to issue a letter indicating that you have entered the Interactive Review Phase. This only happens if the reviewer believes they can make a decision regarding substantial equivalence in the next 30 days. If the decision is to issue an Interactive Review Letter, then the lead reviewer believes that only minor issues remain and there is only the need for interactive email responses between the lead reviewer and the submitter. An interactive review is the ideal outcome of the substantive review process but it rarely happens.

If you receive an Additional Information Request, what are your options?

The AI letter will indicate that you have 10 days to request a clarification meeting with the reviewer. The wording of this section of the AI letter is provided below:

“FDA is offering a teleconference within 10 calendar days from the date on this letter to address any clarification questions you may have to pertain to the deficiencies. If you are interested in a teleconference, please provide (1) proposed dates and (2) a list of your clarification questions via email at least 48 hours before the teleconference to the lead reviewer assigned to your submission. We would like to emphasize that the purpose of the meeting is to address specific clarification questions. The teleconference is not intended for the review of new information, test methods, or data; these types of questions could be better addressed via a Submission Issue Q-Submission (Q-Sub). For additional information regarding Q-Subs, please refer to the Guidance for Industry and FDA Staff on Medical Devices: Requests for Feedback and Meetings for Medical Device Submissions at https://www.fda.gov/media/114034/download.”

If you wait too long to request the teleconference, then FDA will require you to submit a formal pre-sub meeting request or “Submission in Review” (SIR) meeting request. If you request a SIR meeting within 60 days of receiving an AI Request, the FDA will schedule a SIR meeting with you within three weeks of receiving the request–assuming resources are available. If you wait longer than 60 days to request the SIR meeting, then the FDA will default to their normal target of 60-75 days for scheduling a pre-sub meeting. For example, if you submit your SIR meeting request on day 75, and the FDA takes 75 days to schedule the meeting, you will be granted your SIR meeting at 150 days and you will only have 30 days remaining to respond to the AI Request before your submission is automatically withdrawn.

Therefore, it is important to request a clarification meeting immediately after you receive the AI Request. While you are waiting for your clarification meeting, you should immediately begin preparing any draft testing protocols that you want the FDA to provide feedback on during a SIR meeting. Then after you have the clarification meeting, you should submit your SIR meeting request and include any draft testing protocols you have prepared. This may include a statistical sampling rationale, a proposed statistical analysis method, a summative usability testing protocol, or a draft protocol for some additional benchtop performance testing. The FDA can review examples of preliminary data, a protocol, or a proposed method of analysis. The FDA cannot, however, provide a determination of substantial equivalence.

The Most Common Mistakes in Responding to an Additional Information Request

Most companies make the mistake of asking the lead review if they provide specific additional information, “Will this be sufficient to obtain 510(k) clearance?” Unfortunately, the FDA is not able to provide that answer until the company has submitted the additional information and the FDA review team has had time to review it thoroughly. This is done only when the submitter delivers an FDA eCopy to the Document Control Center at CDRH, and the review team is able to review the information. This new information is assigned a supplement number (e.g. S001), and it will typically require three weeks to review the information. Then the lead reviewer may request minor modifications to the labeling, instructions for use, or the 510k summary. This request is an interactive request, and the submitter must respond within a very short period (e.g. 48 hours), and the wording of the request may be “Please provide the above information by no later than COB tomorrow.”

FYI: “COB” means “close of business.” Wow. The FDA loves acronyms.

Best Practices in Responding to an Additional Information Request

If you receive an AI request on a Friday afternoon, 58 days after your initial submission, you should immediately request a clarification teleconference with the FDA reviewer for the following week. The only exception is if you only have minor deficiencies that you feel are completely understood. During the days leading up to the clarification teleconference, your team should send a list of clarification questions to the lead reviewer and begin drafting a response memo with a planned response to each deficiency. After the clarification meeting, you will have approximately 6-7 weeks to submit a SIR meeting request. However, you should not wait that long. Your team should make every effort to submit your SIR meeting request within 2-3 weeks. If the FDA takes 3 weeks to schedule your meeting, then you will have used approximately 6 weeks of your 26 weeks to respond to the AI Request.

In your SIR meeting request, you should always try to provide examples or sample calculations to make sure the FDA review team understands what you are proposing to submit in your supplement. For example, the FDA reviewers do not have enough time to review your entire use-related risk analysis (URRA) in a SIR meeting request. However, you can provide an example of how you plan to document a couple of use-related risks. Then you can show how these risks would translate into critical tasks. Finally, you could provide a draft summative usability testing protocol for FDA feedback. The FDA review team doesn’t have enough time available to review much more. You will only have one hour for your SIR meeting.

How to Prepare Your Response

In section “V” of the FDA guidance on deficiency responses, the FDA recommends that you restate the issue identified by the reviewer in your response. Next, your response should include one of the following:

the information or data requested, or
an explanation of why the issue is not relevant, or
alternate information with an explanation of why the information you are providing addresses the issue.

Before you respond to an AI Request, you should look up any FDA guidance documents referenced in the AI Hold letter to make sure that you address each requirement in the applicable FDA guidance document(s).

The most important technique to learn when you are responding to regulators is to organize your response in a tabular format that is numbered in exactly the same order that the request was made. Typically there will also be sub-parts to certain issues. In that case, you should duplicate the numbers and/or letters of each sub-part and segregate each sub-part in a different row of the table. Personally, I like to alternate the color of the font I use in the table to make it even more obvious which information is a restatement of the reviewer’s comment and which information is the company’s response to the AI Request.

Why you don’t get a second chance to respond to an AI Request

Once you respond to an AI Request, and the DCC receives your FDA eCopy, the FDA review clock will then resume the countdown to 90 days. In our example above, you received the AIR Request on the 58th day. The FDA must review everything you submitted and make a final substantial equivalence decision before the 83rd day because they still need to submit their recommendations to senior management in their branch. If any changes to the labeling, instructions for use, or the 510k are required, you should receive those requests several days before (i.e. 76-83 days). You can respond to interactive requests via email, and then the final SE decision will be made. If you do not respond to all of the deficiencies in the AI Request, the FDA reviewer will not have enough time to request that you address the remaining gaps and finish their review. Therefore, an incomplete AI Response will certainly result in a non-substantial equivalence (NSE) letter.

If you need to respond to an additional information request from the FDA reviewer, we can review your planned response to identify potential gaps. If you need help please use our calendly app to schedule a call with a member of our team.

About the Author

Posted in: 510(k)

Leave a Comment (0) →

What are the secrets to success in responding to an FDA RTA Hold?

Posted by Rob Packard on June 15, 2021

When an FDA reviewer places your 510k on RTA Hold, there are secrets you can learn to improve your chances of a successful response.

Test your knowledge about the FDA RTA Hold process

Did you know that approximately 50% of 510(k) submissions are placed on RTA Hold? Did you know that you can be placed on RTA Hold multiple times for the same submission? Did you know that the 90-day review clock is reset to “0” when you submit your response? Do you know how to respond to the FDA when the reviewer is incorrect? Did you know that you can avoid the RTA screening process for any 510(k) submission if you use the correct template? Every year there are more than 1,000 submissions placed on RTA Hold, but did you know there is an FDA guidance specifically telling you how to respond to deficiencies? You can learn the secrets to responding to an FDA RTA Hold just by reading this article.

What is an FDA RTA Hold?

When the FDA receives a Traditional 510k submission FDA eCopy, the eCopy is uploaded to the FDA system within hours of the submission being received. If the eCopy does not meet the eCopy format requirements, then the submission will be placed upon eCopy Hold. The official correspondent will receive an automated email indicating that the submission is on eCopy Hold, and the submitter will be asked to correct the submission format to meet the eCopy submission requirements and provide a replacement eCopy. If the FDA user fee has not cleared, then the submission will be placed on User Fee Hold. It is possible to be placed on eCopy Hold and User Fee Hold at the same time.

If your eCopy is accepted, then a reviewer is assigned to screen your submission for compliance with the FDA Refusal to Accept (RTA) policy. The reviewer has 14 days to complete this review, and on the 15th day the reviewer must do one of three things: 1) issue a RTA Hold letter to the submitter, 2) issue an RTA Acceptance letter to the submitter, or 3) issue a letter that states the RTA screening was not completed on-time and the submission was automatically accepted. If your receive an RTA Hold letter, it will be via email from the reviewer and the RTA Checklist will be attached. In the checklist, there will some items highlighted in yellow and deficiencies will be noted in those sections. The reviewer may add additional comments to the checklist, but you are only required to respond to the highlighted sections. The process that the reviewer follows for RTA screening is defined in the FDA guidance for the Refusal to Accept process, and the guidance includes a checklist for traditional, abbreviated, and special 510k submissions. Some companies will fill in these checklists themselves and submit a copy of the checklist with the 510k submission. This is intended to help the reviewer identify where all of the requirements in the RTA checklist can be found. Third-party reviewers require that the company complete the RTA checklist and provide it to them with the eCopy.

How many times can you be placed on hold for the same submission?

Technically there is no limit to the number of times a submission can be placed on RTA Hold, and our firm has seen a few submissions placed on RTA Hold twice in a row. The first RTA Hold is referred to as RTA1, and the response to that RTA Hold is referred to as the first supplement (i.e. K123456/S001). If a second RTA Hold is issued, that hold is RTA2, and the response to that RTA Hold is referred to as the second supplement (i.e. K123456/S002). A response to an eCopy Hold is referred to as an amendment (i.e. K123456/A001).

What happens to the 90-day review clock when you are placed on RTA Hold?

When the FDA reviewer places your submission on RTA Hold, the 90-day review clock is automatically reset. Therefore, even if you respond to an RTA Hold on the same day you receive the RTA Hold, and your submission is received the next day, the “real” review timeline is now 106 days instead of 90. If your submission is placed on RTA Hold twice, then the “real” review timeline is now 122 days instead of 90. If the lead reviewer of your 510k requests additional information, this is referred to as an “AI Request.” We will address this in a future blog, but an AI Request does not reset the review timeline. The AI Request, however, will increase the review timeline. Although we rarely have an RTA Hold, we almost always have an AI Request. This is why our average submission is approximately 125 days (i.e. ~30 days are required to respond to the AI Request.

How should you respond if the FDA reviewer is incorrect?

The average 510(k) submission has grown over time from 300 pages to more than 1,200 pages, but the FDA review “clock” is still 90 days and the RTA screening is limited to 15 days. Therefore, it is not reasonable for you to expect the reviewer to understand and absorb every detail of your submission. If the reviewer can’t find the information they are looking for quickly, the reviewer may state that they could not find the information in the submission or that you did not provide it. If the information is found in the submission, you should provide a reference to the section of the submission, including the document and page number, in your RTA response. You may even choose to quote the information in your response memo if it is brief.

Other times the reviewer may not understand why certain information is not relevant to your submission. In this case, you should restate why the information requested is not relevant. You may want to review relevant FDA guidance documents that explain how to justify why information is not required. For example, if you did not provide biocompatibility testing reports for some of the endpoints that are identified in ISO 10993-1:2018, then you should either provide a detailed biological risk assessment in accordance with the FDA guidance on the use of ISO 10993-1, or you should provide a biocompatibility certification statement.

If you are not sure why the FDA reviewer stated the information you provided is not acceptable, you might try calling or emailing the reviewer to ask for clarification. If you do this, be respectful of their time and be brief. You should identify who you are (you must be the official submission correspondent to speak with the reviewer), you should identify which submission you are contacting the reviewer about (they are working on many simultaneously), you should restate the issue identified by the reviewer (it may have been an issue of another member of the review team), and then you should indicate where the information can be found in the submission. If they believe this addresses the issue, then they will instruct you to provide that information in an RTA response. If the information does not address the issue, usually they will explain why. Your chances of receiving an email response are also better than speaking to the person on the phone–especially during the Covid-19 pandemic.

FDA eSTAR submissions are not subjected to the RTA screening process

When you use the FDA eSTAR submission instead of creating an eCopy, your submission should already meet all of the RTA screening requirements. The eSTAR includes automation to validate that the submission is administratively complete and therefore the reviewer does not need to do an RTA screening of an eSTAR submission. Therefore, most companies should realize a shorter overall 510k clearance timelines, because they will only have an AI Request and the review clock will not be reset.

Does the FDA offer any guidance on how to respond to deficiencies?

When the FDA writes deficiencies, the reviewer is supposed to follow the FDA guidance for deficiency content and format. However, the RTA checklist deficiencies typically are shorter and may not be as clear as a deficiency in additional information (AI) requests or non-substantial equivalence (NSE) letters. The first part of the deficiency is a reference to the information that was provided by the submitter (i.e. section, page number, or table). In an RTA checklist, each deficiency is provided in the comments section at the end of the section of the checklist. Therefore, if you have a deficiency related to your device description, the deficiency will be written at the end of the device description section of the RTA checklist. The comment will be highlighted in yellow, and there will be a checkbox next to the specific checklist item indicating that the requirement was not met. In the far-right column of the checklist, there will be a reference to the page of the submission where the deficiency can be found.

In the comment there reviewer should explain why the current information does not meet the requirement of the RTA checklist. The reviewer should also clarify the relevance of the deficiency with regard to the substantial equivalence determination. For the example of a deficiency related to your device description, usually, the issue is that your submission has inconsistencies between the various submissions or there is insufficient detail about your device. At the end of the comment, the reviewer should provide an explicit request for the information needed to address the RTA Hold.

the information or data requested, or
an explanation of why the issue is not relevant, or
alternate information with an explanation of why the information you are providing addresses the issue.

Before you respond to an RTA Hold, you should look up any FDA guidance documents referenced in the RTA Checklist to make sure that you address each requirement in the applicable FDA guidance document(s).

Regardless of how well your response is organized, you must respond within 180 days. On the 181st day, your submission will be automatically withdrawn. The agency has granted extensions of an additional 180 days during the Covid-19 pandemic, but that will end and you should verify if you can obtain an extension from the reviewer rather than assume that this will happen. If the 180th day is on a weekend or US holiday, the Document Control Center (DCC) at the FDA will not receive your submission until the next business day. Therefore, you will need to ship your submission earlier to ensure the delivery is received on time. Since most companies are shipping their RTA response via FedEx or UPS to the FDA, you also will want to make sure you take into account customs clearance for international shipments and local holidays where you are. If you are shipping from the UK, for example, you can’t expect FedEx to ship on a British holiday. If you need help with printing and shipping your RTA response, Medical Device Academy offers an eCopy print and ship service for $99/eCopy (including the overnight FedEx fee).

If your 510k submission was placed on RTA Hold by the FDA, we can help you respond to the deficiencies identified by the FDA reviewer. We can also review your planned response to identify potential gaps. If you need help please use our calendly app to schedule a call with a member of our team.

About the Author

Posted in: 510(k)

Before 510k clearance, 10 quality tasks you need to prevent unexpected delays

Posted by Matthew Walker on May 20, 2021

The US FDA does not require that 100% of your quality system be implemented before 510k clearance, but these 10 activities need to be done.

The form above allows you to register for a live webinar we are hosting on Friday, May 21, 2021 @ 1 pm EDT. The webinar will share the 510k project management lessons learned by our team since 2016. In addition to 510k project management, MedTech companies also need to implement their quality system in parallel with their regulatory submissions. Some people say that you need to implement your quality system before you submit your 510k. That is not an FDA requirement, but you do have quality system activities that need to be done before you will have all of the technical documentation you need to submit a 510k. This article describes 10 quality tasks you need to prevent unexpected delays.

Design & Risk Management Planning

Design & Risk Management Planning is your 1st priority because you want to identify all of the major activities that need to be completed in your design and risk management processes and which activities are critical path items. Otherwise, you will have unexpected delays. You can and should add details to the plan as you go, but items 2-9 listed below should be included in that initial plan–along with your design and risk management activities.

Risk Management Activities are Needed Before 510k Clearance

Risk Management is your 2nd priority because it’s an input to almost everything else listed below – this includes hazard identification, creating a use-related risk analysis (URRA), and identifying cybersecurity risks if you have software/firmware. Reference: ISO 14971:2019 Medical devices — Application of risk management to medical devices. Cybersecurity depending on the device should evaluate security as an overlapping but separate area from risk management. (Reference AAMI TIR57: 2016 Principles For Medical Device Security – Risk Management.)

Formative Usability Testing

Formative Usability Testing is your 3rd priority because this helps you evaluate your device design while it’s still evolving. Formative testing helps you identify opportunities for improvement, provides confirmation that your design is moving in the right direction, and identifies potential use errors while there is still time to implement effective risk controls such as alarms and other safety features. References:

Software Validation is Needed Before 510k Clearance

Software Validation is your 4th priority because it must precede electrical safety testing for electromedical devices and most companies underestimate the time required to document software validation in accordance with IEC 62304:2006 / AMD 1:2015 and the FDA’s five guidance documents:

Supplier Qualification is Needed Before 510k Clearance

Supplier qualification is your 5th priority because you do not want to order all of your prototype parts for the initial testing parts and then find out that the supplier is not capable of supporting you commercially. If you have to switch suppliers you might be forced to repeat biocompatibility testing and other design verification testing due to changes in the manufacturing process. Implementation of a supplier qualification process before 510k clearance is needed.

Label & IFU Requirements Specifications

Label requirements and instructions for use requirements specifications is your 6th priority because you cannot perform electrical safety testing or design validation (including summative usability testing) of your device without labeling and instructions. These requirements are the design inputs for information provided to the user and these must be controlled under design controls rather than document control.

Packaging Specifications

Packaging specifications is the 7th priority you should implement before 510k clearance because the packaging is needed to maintain sterility, to ensure product stability, and to protect the product from shipping. Companies are also frequently surprised by the long lead times associated with ordering custom packaging and you may not have the budget to validate sub-optimal “stock” packaging for your 510(k) submission and then repeat the validation for the optimized packaging later.

Quality System Implementation

Quality system implementation is the 8th priority for implementation before 510k clearance because you will need a fully functional quality system by the time your 510(k) is cleared. Quality system implementation typically takes 6+ months while the 510(k) review should take 4 months or less. Quality system implementation includes writing 25+ procedures, reviewing and approving those procedures, training your employees, and actually using those procedures to begin generating quality system records. For companies that are pursuing Canadian Licensing or CE Marking, the quality system must be fully implemented and certified before the regulatory submission is possible. (Quality System Requirements for the U.S. FDA are outlined within 21 CFR 820-Quality System Regulation)

Summative Usability Testing

Summative usability testing should happen after Design Freeze or you risk having to backtrack in your design process if this validation test reveals a need for device changes. The FDA’s 2016 Usability Guidance explicitly defines this validation testing as just a portion of overall design validation. (Reference Applying Human Factors and Usability Engineering to Medical Devices Guidance for Industry and Food and Drug Administration Staff (2016))

Apply for Small Business Status Before 510k Clearance

Application for small business status should be the 10th priority for implementation before 510k clearance because this can save your company $9,000+ but it requires that you submit your application at least 60 days before you need to pay the 510(k) user fee.

About the Author

Matthew Walker – QMS, Risk Management, Usability Testing, Cybersecurity

Matthew came to us with a regulatory background that focused on OSHA and NFPA regulations when he was a Firefighter/EMT. Since we kidnapped him from his other career, he now works in Medical Device Quality Management Systems, Technical/Medical Writing and is a Lead Auditor. He is currently a student in the Champlain College’s Cybersecurity and Digital Forensics program, and we are proud to say that he is also a member of both the Golden Keys and Phi Theta Kappa Honor Societies! Matthew participates as a member of our audit team and has a passion for risk management and human factors engineering. Always the mad scientist, Matthew pairs his professional life in regulatory affairs with hobbies in the culinary arts as he also holds a Butchers/Meat Cutters certificate from Vermont Technical College.

Email: Matthew@FDAeCopy.com

Connect on Linkedin: http://www.linkedin.com/in/matthew-walker-214718101/

Posted in: 510(k)

Leave a Comment (0) →

What is 510k Content Format

Posted by Rob Packard on July 5, 2020

This article defines the 510k content format for an FDA 510k pre-market notification submission in accordance with the September 13, 2019, FDA guidance.

What is a 510k?

A 510k submission is a pre-market notification submission to the FDA. The “510(k)” designation refers to the applicable section and sub-section of the Food Drug & Cosmetic Act. The “pre-market” designation is a reminder that companies must submit a 510k submission before marketing their products. Finally, the “notification” part of the phrase is used instead of the word “approval” because the FDA does not consider the 510k review process to be an endorsement or approval of your product. Instead, the 510k review process is a review by the FDA to determine if your product meets the requirements of substantial equivalence with a predicate device. The FDA initially performs a prescreening of the 510k submission to verify that it meets the minimum requirements for 510 content format. Then during the 510k substantive review process, the reviewer must answer six questions in the substantial equivalence decision tree:

Is the predicate device legally marketed?
Do the devices have the same intended use?
Do the devices have the same technological characteristics?
Do the different technical characteristics of the devices raise different questions of safety and effectiveness?
Are the methods acceptable?
Do the data demonstrate substantial equivalence?

The 510k process was not intended to be the primary process for regulatory approval by the FDA. The 510k process was intended to be a simplified approach for clearance of devices that are of moderate-risk and similar in design and intended use to another moderate-risk device that is already on the market. However, the process was manipulated as a loophole by device companies to avoid the more rigorous pre-market approval (PMA) process that requires conducting a clinical investigation.

Recent changes to the 510k review process are much deeper than the 510k content format

In approximately 2010, the FDA gradually started making changes to the 510k process. The FDA started publishing more guidance documents specifying both collateral guidance documents that apply to all device classifications (e.g., biocompatibility and human factors ), and particular guidance documents that apply to only a small number of product classifications (e.g., CADe). In 2012, the FDA implemented a new policy called the Refusal to Accept (RTA) Policy for 510(k)s. The FDA implemented this policy to improve the general quality of 510k submissions. All submissions are now subject to a 15-day review of the 510k content format to ensure that the submission includes all 20 required sections required by the FDA, the submission includes a table of contents and page numbering, and the various sections of the 510k include basic elements that are frequently forgotten by companies. Initially, more than 60% of the 510k submissions were rejected during the RTA screening process. Still, submissions have improved, and training of the FDA personnel performing the RTA screening has resulted in a more consistent application of the RTA policy. The FDA also systematically converted each of the remaining Class 3 devices that were eligible for 510k clearance to Class 3 devices requiring a PMA. The most recent changes were the elimination of requiring the submission to include a printed hardcopy of the submission (i.e., FDA eCopy only) and no longer allowing predicates that are more than ten years old.

FDA requirements for 510k Content Format

The FDA requires that your 510k submission is organized into 20 sections as described in section V of the table of contents of the September 13, 2019, FDA 510k guidance document. The FDA no longer requires a hardcopy of the submission. Now the FDA only requires an electronic copy (i.e., FDA eCopy) with a hardcopy of the 510k cover letter. The cover letter may be included in the eCopy, but it is not required. The FDA eCopy guidance document was updated on December 16, 2019.

The FDA eCopy guidance gives you the option of organizing the 20 sections of a 510k into 20 volumes with multiple documents in each volume or to submit sequentially numbered documents. The word “volume” refers to electronic folders in the FDA eCopy rather than physical binders. There is no right or wrong choice regarding volumes—if your eCopy uploads. The answer to this question is personal preference. The FDA recommends that multiple volumes be used for more extensive submissions, but using the same process for every 510(k) submission makes submission teams more efficient. It also is more comfortable for the FDA to navigate between documents when they are not in separate volumes. Therefore, the document structure is generally best for the FDA, and the volume structure is usually best for the company to prevent the need for renumbering files and file names. We always use the volume structure for every submission, even pre-submissions. Submissions are organized into 20 volumes to match the 20 sections of a 510k submission. If we include an RTA Checklist, then we add a 21st volume. The FDA recommends using the 21st volume for miscellaneous appendices, but the volume structure of the submission makes it easy to insert miscellaneous content directly into the applicable sections by adding documents after the initial section summary document.

Overall Numbering or Numbering within Sections?

Again, this is a personal preference. However, there are always last-minute changes to documents. Therefore, whichever numbering system you use should minimize the need for the last-minute renumbering of the entire submission. This is especially painful when you number the overall submission, and then you add a page to the middle of the submission when you are trying to ship out your submission that day. By numbering only the sections, you reduce the amount of rework required. Our firm deviates slightly from the “numbering within sections” requirement. In the table of contents, we indicate how many pages are associated with each document in a volume, and then we start each document with page 1. One FDA reviewer recently requested that we modify this to “page x of y,” where “x” is the page number of that document, and “y” is the total number of pages in the document. Therefore, we updated all of our templates to reflect the “page x of y” format for page numbering.

510k Format Content: Using Your Table of Contents for Project Management

When I was less experienced, I used project management software and action item lists to manage submission projects. Experience has taught me to simplify. Now I only use an action item list to track the progress of individual tasks. To track the overall submission, I now use the table of contents as my project management “report.” If you color-code the rows of your table of contents, you can communicate the status of each document in the submission. At the beginning of the project, all the rows indicate documents are not yet started—signified by the color red. Once I being a document, I change the color to yellow. Finally, when the document is completed, I change the color of the row to green. Three documents require the signature of the official correspondent with the FDA:

510k Cover Letter
Certification Regarding Confidentiality
Truthful and Accuracy Statement

Once these three documents are completed, they still need a signature that should only be applied just before we prepare the eCopy. Therefore, I signify the status of documents waiting for signatures with blue rows. A couple of people struggle with reformatting row colors, but every single person on your team will understand that they want the table of contents to gradually change from red, to yellow and finally to 100% green.

Posted in: 510(k)

Leave a Comment (0) →

NSE letter: A CAPA plan for your 510k process

Posted by Rob Packard on April 28, 2020

Cry, complain, call the reviewer…you might feel a little better, but you received an NSE letter, and tomorrow you still can’t sell your device.

NSE Letter NSE letter: A CAPA plan for your 510k process

Instead, try approaching an NSE letter like a CAPA investigation. What is the issue? The FDA determined that your device is not substantially equivalent to the predicate you selected. What is the root cause? There are four (4) possible root causes.

NSE Letter Cause #1: You failed to verify that the predicate is a legally marketed device.

If your predicate device is not legally marketed, you need to select a new predicate and resubmit. However, it is doubtful that your device would pass the refusal to accept the (RTA) screening process if the predicate was not legally marketed. If your predicate was not registered and listed with the FDA (check using this link), then you should have submitted a pre-sub request to determine if the agency has any problem with using the device you chose as a predicate. This is an essential question if the manufacturer is no longer in business, and the product is no longer for sale.

NSE Letter Cause #2: You failed to evaluate the substantial equivalence of your device’s intended use with the predicate.

The intended use of your predicate device is documented for every potential predicate since February 1992 on FDA Form 3881–which you can download along with the 510k clearance letter for the predicate. There is also an intended use documented for every device category in the applicable regulation for that device. This intended use is more generic than FDA Form 3881, but both are applicable. The FDA Form 3881 you submit for your device must be equivalent. I recommend a point-by-point comparison with regard to the following elements: 1) OTC vs. prescription use, 2) user, 3) patient population, 4) illness or medical condition, 5) duration of use, 6) environment of use and 7) target part of the body. Any difference can raise new issues of risk and may result in an NSE decision. However, the FDA typically will work with the company to modify the wording of FDA Form 3881 to ensure the intended use is equivalent or to make sure you provide clinical evidence to address the differences. In my pre-submission requests, I include a comparison document for the intended use to ensure that the FDA is aware of any differences in the intended use.

Cause #3: You failed to convince the FDA that technological differences do not raise different questions of safety and effectiveness.

Unless your device is identical in every way to the predicate device, you will have to persuade the FDA that differences do not raise questions of safety and effectiveness. At the beginning of the 510(k) process, it is helpful to document technological differences systematically. Specifically, this should include: 1) materials, 2) design, 3) energy source, and 4) other features. For each difference, you must justify why the difference does not raise different issues, or you must provide data to prove it. It is also possible that you were not aware of questions of safety and performance raised by technological differences. To avoid this problem, you can submit a detailed device description and draft labeling to the FDA in a pre-sub meeting request. If you ask questions about differences in a pre-sub meeting, you can avoid an NSE letter.

Cause #4: You failed to provide data demonstrating equivalence.

For each difference, you should determine an objective method for demonstrating that the difference is equivalent in safety and performance to the predicate. Your test method can be proposed to the FDA in a pre-sub request before testing. The FDA sees more than 3,000 companies propose testing methods to demonstrate equivalence each year. They have more experience than you do. Ask them in a pre-sub before you test anything. There may be a better test method, or you might need to adjust your test method. Sometimes results are unclear, but there might be another test you can perform to demonstrate equivalence, and then you can resubmit your 510k. Possibly you were unaware of the need to perform a test, and you were unable to complete a test within the 180 days the FDA allowed for submitting additional information. The good news is you now have all the time you need.

What is similar between all four causes of the NSE letter?

In all four root causes identified above, you could benefit greatly from the pre-sub meeting. Now you have an NSE letter, and you know which of the four reasons why your submission did not result in 510(k) clearance. However, the correction to your NSE letter may not be clear. Therefore, you should consider requesting a pre-sub meeting as quickly as you can. Most companies choose not to submit a pre-sub meeting request because they don’t want to wait 60-75 days. However, sometimes pre-sub meetings are scheduled sooner. In addition, 60-75 days is not as costly as receiving a second NSE letter.

Prevent a future NSE letter by requesting a pre-sub meeting

Regardless of your corrections for the current NSE letter, you should prevent future occurrences by planning to submit a pre-sub meeting request for every submission. I try to help clients gather all the information they need without a pre-sub meeting, but each new 510k reminds me why a pre-sub meeting is so valuable. You always learn something that helps you with the preparation of your 510k.

Help with Pre-sub meeting requests

The FDA published a guidance document for pre-sub meeting requests. If you need additional help, there is a webinar on this topic.

Posted in: 510(k), CAPA, Design Control

Leave a Comment (0) →

Reprocessed Single-Use Devices – Optimizing 510(k) preparation

Posted by Mary Vater on April 15, 2020

This article explains the challenges reprocessors face in obtaining 510(k) clearance for reprocessed single-use devices when they are not the OEM.

Guidance for Reprocessed Single Use Devices Reprocessed Single Use Devices Optimizing 510(k) preparation

With increasing pressures on the medical device industry to make healthcare more affordable, there has been a push to reprocess and reuse single-use devices. Reprocessors obtain used devices from healthcare facilities. The reprocessors clean, process, resterilize, repackage, and relabel devices. Reprocessors must obtain FDA 510(k) clearance by demonstrating that the safety and effectiveness of the reprocessed device are substantially equivalent to the single-use device produced by the original equipment manufacturer (OEM). The FDA also released a guidance document regarding reprocessed single-use devices.

Obtaining 510(k) clearance for a device your company did not design can be challenging because information requirements that are trivial for the OEM can be extremely difficult to provide for a reprocessor of the device. The following sections of a 510(k) submission pose unique challenges for reprocessed single-use devices:

Section 13, Labeling – What should and should not be included in the reprocessed device labeling
Section 15, Biocompatibility – How to identify the materials, and determine what biocompatibility testing needs to be done
Section 18, Performance Testing – Strategies for determining appropriate performance testing

Section 13, Labeling of reprocessed devices

Labeling of reprocessed devices consists of the instructions for use and the packaging label(s). Device package labeling may also direct the user to both the reprocessor’s IFU and the OEM’s IFU. If you are referencing the OEM’s IFU, it is also important to include the OEM’s model number. Instructions for use should consist of:

Indications for use, which must be equivalent to the OEM indications.
All of the necessary warnings and cautions and basic operating instructions needed to operate the device safely.
The instructions for use may also instruct the user to reference the OEM instructions for use for additional information.
Instructions on the handling of the device after use, with the likelihood that the device will be returned to the reprocessor to repeat the cycle.

Section 15, Biocompatibility

Biocompatibility data is more challenging to provide if you replace or modify original components. If reprocessing does not modify the OEM device whatsoever, you can claim that the materials are identical to the OEM device. Therefore, the reprocessed device does not require biocompatibility testing. However, the reprocessor still needs to evaluate the biological risks associated with the reprocessing of the device by testing for cleaning and sterilization residuals. This involves testing for cleaning agent residuals and EO residual testing (ISO 10993-7), if applicable.

If you replace any of the components during reprocessing, with a new component that is identical in dimension and material to the OEM component, minimal biocompatibility testing will be required. If the exact material used by the OEM is unknown, reprocessors can perform material identification testing to determine the material used, and then create the replacement part out of the same material.

If you modify or replace any patient-contacting components on the device such as lubricants, insulation, etc., with components that are different from the OEM, then you will need to perform additional biocompatibility testing to prove that the new or modified material is biocompatible. This testing will depend on the duration of contact and where will the material contact the patient. The new material will also need to be listed in your device description and Section 15 of your 510(k) submission.

Section 18, Performance Testing

There are three primary sources for identifying performance testing requirements of reprocessed devices:

OEM Testing listed in the OEM 510(k) submission
Predicate Testing listed by another reprocessor of an equivalent device
Product Standards listed under the product classification code for the reprocessed device or the OEM device

You should reference a predicate device that has been reprocessed and the OEM device to identify performance testing. Some testing is specific to the functional performance of the device. For these tests, you need to compare performance side-by-side against the OEM. Another testing is specific to the reprocessing, and you will reference the predicate device. Sources of information regarding the required tests for each of these devices can be found in the 510(k) summaries of the respective devices. If possible, it’s helpful to select a predicate that has a redacted 510(k) available on the FDA’s website. If a redacted 510(K) is not readily available, you may request a redacted copy through the freedom of information act on-line. A redacted copy of the OEM 510(k) is also helpful.

If testing information is not as readily available in the 510(k) summary, you will determine the essential performance functions of the device, and design tests to evaluate and compare the OEM device and the reprocessed device for those functionalities. Some devices have specific standards for the design and/or testing of the device. To determine if the reprocessed device has any applicable standards, you should search the product code of the reprocessed device, as well as the product code of the OEM device if they are different, in the FDA product classification database. Recognized standards applicable to the reprocessed device will be listed in the search results.

Additional tests that may be needed to validate reprocessing include residual protein, residual carbohydrates, and the presence of hemoglobin. These tests ensure that all biological material from previous use is removed. If you are not performing biocompatibility testing on the reprocessed device, you also need to do a chemical test to ensure no residual detergent or cleaning residues are remaining on the device. You also need to determine how many reprocessing cycles the device can survive before performance degradation. This can be done by repeating simulated use, reprocessing, and performance testing until a statistically relevant decrease in the performance of the device is observed.

If you have additional questions regarding the preparation of your 510(k) submission, you might be interested in a course Mary Vater and Rob Packard created for AAMI. Rob Packard will be the lead instructor for the course pilot in May: 510(k) training course. You can also schedule a call with us by clicking the button below.

Posted in: 510(k)

Leave a Comment (0) →

eCopy Guidance is Finally Updated by FDA

Posted by Rob Packard on January 5, 2020

This blog summarizes the changes in FDA policy, released on April 27, 2020, as a new eCopy guidance for device manufacturers.

The date of the guidance above was updated, but the changes to the guidance do not represent any changes in policy. It is an update of contact information and a note regarding eCopies for EUA requests. In August 2016, I had a frustrating week where I had three (3) different submissions placed on eCopy hold by the FDA, three (3) separate times, for a total of nine (9) eCopy hold in the same week. That resulted in an extra $175 of FedEx charges and wasted six (6) USB flash drives. The biggest problem was the submission delay experienced by each client that week, which wasn’t very comfortable. This terrible, no good, dreadful week ultimately resulted in our company creating a new productized service–preparing FDA eCopies for clients and competitor consultants. We also became international experts on the FDA eCopy guidance. If my experience was this painful, there must be other people experiencing the same problem, or many people would experience this problem as soon as they tried to submit their next filing with the FDA.

For about 18 months, we helped many companies prepare FDA eCopy submissions, but then there was a government shutdown, and the FDA unofficially changed its policy. A printed paper copy of pre-submissions, 510ks, and De Novo classification requests would no longer be required. You only needed to print a paper copy of your cover letter and include an electronic copy on a CD, DVD, or USB flash drive. Despite this policy change, many clients still requested the printed copy because the FDA legislation was not yet changed, and there was no updated guidance. We explained to each client that the policy had changed, and only two clients asked us to print the paper copy anyway.

In October of 2018, the unofficial policy became official, but there was still no updated FDA eCopy guidance for us to share with clients. This situation frequency resulted in questions from clients about how they should phrase the “eCopy Statement” in their submission cover letter. The eCopy guidance that was current in 2018 stated that you should include the following phrase in your cover letter: “This submission includes an eCopy and a paper copy. The eCopy is an exact duplicate of the paper copy.” However, the paper copy consisted only of the cover letter, and the rest of the submission was solely provided in electronic format.

The FDA released a new pilot version of the eSubmitter software to help companies prepare 510(k) submissions and to streamline the FDA review of submissions in 2018. However, even electronic submissions prepared with eSubmitter must be sent by courier or mail to the FDA Document Center. In 2019, the FDA mentioned that they would be releasing new guidance documents regarding electronic submissions. Still, we were also told that the FDA has no near-term plans to enable companies to submit pre-submissions, 510ks, or De Novo classification requests to the FDA via an electronic submissions gateway (ESG).

Finally, on December 16, 2019, the FDA released a new eCopy guidance. The eCopy guidance was updated again on April 27, 2020, but the changes are updated to include emails, updated webpages, and a note regarding EUA requests.

July 2022 Update for the FDA eCopy process

The FDA created a Customer Collaboration Portal (CCP) for medical device manufacturers. Originally, the portal’s purpose was to provide a place where submitters can track the status of their submissions and verify the deadlines for each stage of the submission review process. Last week, on July 19, the FDA emailed all active FDA CPP account holders that they can upload both FDA eCopy and FDA eSTAR files to the portal 100% electronically. Since our consulting team sends out submissions daily, everyone on the team was able to test the new process. If you have a CCP account, you no longer need to ship submissions via FedEx to the Document Control Center (DCC).

What DID NOT change in the new eCopy guidance?

The file name requirements are identical. You can still organize your submission in volume structure or document-only structure. You are still limited to PDF file sizes of 50 MB. The eCopy will still be problematic for the FDA to upload if your submission exceeds 1 GB. You still need to ship your eCopy to the FDA Document Center unless you submit it to CBER instead of CDRH. You can and should continue to use the eCopy validation software module provided by the FDA to ensure that your eCopy will properly upload. The guidance barely changed in length; it’s just a few pages shorter now.

What DID change in the new eCopy guidance?

Only two things changed in the new guidance. First, there is no mention of an eCopy statement anywhere. Second, you must submit a cover letter ~~in paper format~~ (replaced by Zip file to FDA CCP), but it does not need to be included in the electronic format (that’s only recommended).

The “new” eCopy process is not any easier than the process we have used since February 2018. However, we did update our cover letter template. If you would like a copy, please register for our FDA eCopy webinar.

Should you create your own eCopies, or should you outsource?

If my job was Director of Regulatory Affairs (or a similar position), I would outsource. Regulatory managers in companies are swamped with trying to remain compliant with new and revised medical device regulations and changes to applicable standards.

Does it take one hour to create an eCopy?

No, we can prepare, validate, and upload an FDA eCopy in less than 15 minutes. This is only possible because we do this almost every day. On the last business day before the end of the FDA fiscal year (September 30), we average four (4) submissions on that day alone. We know exactly what to do, we know how to fix all of the most common errors, we know our validation software module is up-to-date~~, and we never run out of USB flash drives~~ (replaced by Zip files to FDA CCP).

How long could it take you to create an eCopy?

If you haven’t done an eCopy in that past year, it could easily take you all day to create an eCopy. You have to read the new eCopy guidance document. You must format your submission according to the rules and proofread 100% of the folder and file names. ~~You need to find a new flash drive. You need to save the submission on your USB flash drive.~~ You need to run the eCopy validation software module.

Or you could just outsource your eCopy problems.

Posted in: 510(k)