2018: A Year of FDA Regulatory Changes to the 510(k) Process and Why they Matter to You.

2018 was a year filled with regulatory changes as FDA made an announcement on “transformative new steps to modernize FDA’s 510(k) program.” There is much commentary in the trade press on this announcement which we will address later in this blog post. There are also many other changes that have been made to the 510(k) pathway this year, and some may impact you sooner, rather than later. This piece outlines those changes that you should be aware of.

January 2018: 

FDA Publishes Draft Guidance on Laser Products

For those of you with medical devices incorporating a laser, FDA intends to “amend its standards for laser products at 21 CFR 1040.10 and 1040.11 to harmonize many of its requirements with those of the IEC.” The IEC is the International Electrotechnical Commission, which is the international standards and conformity assessment body for all fields of electrotechnology.

FDA Publishes Final Guidance on their Refuse to Accept Policy for 510(k)s

The Refuse to Accept (RTA) policy is applicable to every 510(k) and this guidance update in January replaced the 2015 guidance. The changes focused on disclosure requirements for combination products that include a drug component. It also published revised checklists and should be your go-to source for ensuring your 510(k) submission gets through the RTA process without delay. A full 1/3 of 510(k) submissions fail FDA’s RTA review on the first cycle, delaying clearance and starting the submission off on the wrong foot with your review team. 100% of the 510(k)s created in Right Submission’s platform have cleared the RTA review on the first pass.

February 2018:

Final Rule on Human Subject Protection; Acceptance of Data from Clinical Investigations for Medical Devices

FDA amended regulations under 21 CFR Parts 807 and 812 in order to ensure quality and integrity of clinical data and to protect human subjects. The FAQ applies to all clinical data and seeks to standardize requirements for what is adequate clinical data, due in part to increased reliance on data collected outside of the US (OUS).   Clinical investigations must comply with good clinical practice (GCP) requirements, include a review by an independent ethics committee, and have informed consent from subjects if the data generated will be used to support an IDE, 510(k), De Novo, or PMA.

Changes to the eCopy process

Also, in February, in an unofficial change not seen in regulation or guidance, FDA is accepting eCopy 510(k) submissions with only a printed cover letter along with the full electronic submission. If you were intending to print your entire 510(k), this change will benefit you.

April 2018:

Draft Guidance on Expansion of the Abbreviated 510(k) Program

Published in April of this year this draft guidance proposes expanding the Abbreviated 510(k) approach for demonstrating substantial equivalence to some well-understood device types. This “least burdensome approach” would allow certain manufacturers to demonstrate substantial equivalence using objective performance criteria rather than through a direct comparison to a predicate device as is traditional in premarket notifications. A predicate would still be identified, but performance testing would be conducted using recognized consensus standards. This would also decrease reliance on comparative testing to what could be old and outdated technology for a predicate device, a theme which will come up later in this document. 

MultiFunction Products

April also included publication of new draft guidance on multiple function products, those devices with several functions some of which being subject to FDA’s regulatory oversight and some which are not.

May 2018:

Draft guidance on Test Reports for Non-Clinical Bench Performance Testing

This draft guidance recommends that for submissions that contain non-clinical bench testing, the complete test report should be included as well as a summary that describes the test preformed, the objective, methods and procedures, justified pre-defined pass and fail criteria, a summary of the results, and a discussion of the conclusions. We hope that you are already utilizing best practices, but this guidance is of value in reviewing this critical section of a submission.

June 2018:

Finalization of 510(k) exemptions for Certain Class II devices

FDA published a notice in the federal register providing premarket notification exemptions for some Class II devices. However, this only impacted a limited number of devices including 25-hydroxyvitamin D mass spectrometry test systems, genetic health risk assessment systems, endoscope disinfectant basins, UV water purifiers, or vibrators for therapeutic use. This is a much smaller set of devices than the more that 1,000 devices exempted in their July 2017 notice.

Draft Guidance on the Q-Sub Program

The Q-Submission Draft guidance will supersede the existing final guidance and provides a summary of methods one can use to obtain feedback and request meetings with FDA with respect to 510(k)s and other submissions. We recommend early FDA interaction for most submission projects to minimize clearance risk to save time and money.  Using a regulatory information management (RIM) system designed specifically for the medical device industry, such as RIMSYS, allows the ability to track notes, decisions, tasks, communications and regulatory documents associated with FDA interactions and other government submissions.

August 2018:

FY2019 MDUFA User Fees Announced

FDA announced the MDUFA User Fees for the 2019 fiscal year (October 1, 2018 through September 30, 2019). Increasing somewhat from 2018, the impact to you will be minimal. The 510(k) MDUFA User Fee increased from $10,566 to $10,953 The fee for a small business increased from $2,642 to $2,738. Much more significant was the change you saw in from 2017 to 2018 where the MDUFA User Fee for a 510(k) more than doubled. 

 September 2018:

Consensus standards

In two publications (Recognition and Withdrawal and Voluntary Standards) FDA provided guidance on the use of voluntary consensus standards in premarket submissions, including 510(k) submissions. This is applicable if you will include a Declaration of Conformity to a FDA recognized standard or for general use.  FDA also provided draft guidance on the recognition and withdrawal of voluntary consensus standards, pertinent if you are seeking to utilize a standard that is not currently recognized by FDA.

eSubmitter software

FDA also announced a Quik Review Program piloting use of their eSubmitter software in a very limited number (38) of well-understood product codes. The eSubmitter software helps to manage submission content and folder structure but does not help to build high-quality content of a submission like Right Submission’s software for regulatory submission (click here to see our online demo or signup for a live demo). In addition, while a full paper copy of a Quik Review Pilot submission is not required, sponsors must still mail in a CD or thumbdrive of the submission according to traditional eCopy requirements. FDA did create a 60-day review goal (versus the traditional 90-day review period) for these pilot submissions and interactive review rather than AI (Additional Information) requests. However, the product categories are ones in which FDA should not have trouble in reviewing in 60 days regardless of submission format. This is unlikely to impact you as the pilot is limited, but it does point to a future of electronic submissions closer to eCTD on the pharma side.

Third Party Review Program

In final guidance, FDA provided a discussion of Benefit-Risk factors considered when determining substantial equivalence in 510(k) submissions for devices that have different technological characteristics than their predicates. FDA feels that this guidance will be helpful if you are seeking clearance for a device through substantial equivalence to a predicate, but with increased risk and increased benefit or decreased risk and benefit compared to the predicate.

The Special 510(k) Program

In draft guidance for the Special 510(k) process FDA announced that they intend to expand the Special 510(k) program to evaluate certain changes to Indications for Use and technology that are currently not within the scope of the program. This will impact you if you are modifying your own legally marketed device. 

Proposed Rule on Electronic Format for Submissions

In September FDA published a proposed rule proposing to amend requirements to remove paper and multiple copies for premarket submissions and replace them with a single electronic format submission. While this is a step in the right direction to improve the efficiency of premarket submission process, we feel that the proposed rule does not go far enough to improve the process.

October 2018:

Consensus standards

FDA updated its lists of recognized consensus standards for use in IVD and other device submissions. This is likely to impact you if you deal with IVD, orthopedic, certain materials (biocompatibility, titanium, poly(lactide) polymers and others) , and some other areas. Of course, utilizing a submission platform such as Right Submission’s 510(k) platform will ensure that you have an up-to-date database of FDA recognized standards to seamlessly pull into your submission.

Cybersecurity Recommendations

Much anticipated, FDA updated the 2014 cybersecurity guidance with draft guidance, defining a two-tier cybersecurity risk categorization system (high versus standard) for devices, and specific documentation requirements for each tier. This draft guidance also introduces a Cybersecurity Bill of Materials which lists software and hardware components that could be susceptible to cybersecurity vulnerabilities.

November 2018:

FDA Statement on Modernizing the 510(k) Program

FDA’s November 26th announcement comes on the tail of some mainstream media focus on the foibles of this forty-two-year-old system by which the majority of medical devices come to market in the largest global market. The Netflix documentary The Bleeding Edge along with the International Consortium of Investigative Journalists report published just one day before the FDA announcement are indicative of the growing public awareness of issues with medical device safety and concerns with the premarket approval process.

CDRH announced it will consider publishing a list of cleared devices and manufacturers that used predicate devices over 10 years older than the subject device, proposed to sunset certain older predicates, and requested public feedback on their approach. The trade press has responded harshly to the public shaming of devices with predicates over 10 years, arguing that they may be the best predicates regardless of age and that FDA themselves has cleared these devices.

Final guidance on this “Safety and Performance Based Pathway,” as FDA has named it, is expected in early 2019 FDA would “like this efficient new pathway to eventually supplant the practice of manufacturer comparing their new device technologically to a specific, and sometimes old, predicate device.” Therefore you may see more of a focus on safety and performance based comparisons to predicates rather than direct comparisons.

And FDA believes its approach may increase De Novo use rather than 510(k)s. Industry has, on the whole, avoided the De Novo pathway. But as technologies evolve, it has become more difficult to identify a predicate device that has similar intended use and technological characteristics to support a substantial equivalence decision. This also aligns with changes in the regulatory environment in Europe, with many experts expecting MDR to result in less use of predicates. With more submissions requiring pre-marketing clinical evidence because of the new requirement for access to full technical information on a predicate, which would be difficult to obtain if the predicate manufacturer is one of your competitors.

December 2018:

MDUFA Performance Data Published

A rich source of data, the MDUFA Performance reports (MDUFA III and MDUFA IV) tell us that FY2018 saw 3,463 510(k) submissions (a small decrease from 3,841 in FY2017). This means that about 10 new devices are coming to market every calendar day and emphasizes the importance of earlier clearance for your devices. You may find the Right Submission free tool that allows you to search FDA’s database of cleared devices by Indication For Use (which you cannot at the FDA website) useful to improve your competitive landscaping and predicate identification and review.

In both FY2017 and FY2018, ~85% of 510(k)s were determined to be substantially equivalent. A flat trend, but alarming in that a great deal of money and effort is being put into 510(k)s that are not successful and therefore not commercially valuable.

In FY2018, 1,108 submissions of 3,283 were not accepted in the first cycle of Refuse to Accept Review. This means that a full 1/3 of submissions are deficient in some way (at least in the eyes of FDA) and we do hope that you consider a software submission platform such as Right Submission’s, with a 100% record of acceptance in the first round of the RTA review, in order to ensure that your submission is administratively complete.

Improvements to the De Novo Pathway

December also saw the publication of the De Novo Classification proposed rule which, combined with the November press release on safety- and performance-based review, may well point to you being involved in more De Novo rather than 510(k) submissions in the future.

Breakthrough Devices Program

To round out the year, on December 18th FDA published their Breakthrough Devices Program guidance document. This program includes aspects of FDA’s Priority Review Program and Expedited Access Pathway. To access this pathway a device must provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions and either represent a breakthrough technology or is a device for which no approved or cleared alternative exists or offer significant advantages over existing approved or cleared alternatives or the availability of which is in the best interest of patients.  If your device meets these criteria then this pathway may offer a faster path to 510(k) clearance (or De Novo or PMA) as breakthrough designation grants priority review and timely feedback.

About Right Submission: 

Right Submission enables medical device regulatory professionals to create higher quality content by bringing automation, project management, and collaboration to regulatory submission creation and publishing.


About RIMSYS: 

RIMSYS is a Regulatory Information Management (RIM) platform designed specifically for the medical device industry.  RIMSYS offers a suite of cloud-based regulatory affairs software solutions to simplify and manage global product registrations, standards, essential principles requirements, regulatory documents, changing regulations and more.


 About the Author:


Marek Herrmann-Nowosielski, the CEO of Right Submission LLC, has had an extensive career leading R&D, product development, operations, engineering and commercialization organizations and activities for established and venture funded companies in highly regulated industries, including leadership roles at GE, DuPont, Oasys Water and Heartland Technologies.

He is a Fellow of the Institute of Chemical Engineers, a registered Professional Engineer and holds MA, MSc, MEng and MBA degrees.